Biofouling and me: My Stockholm syndrome with biofilms

Journal Pre-proof Biofouling and me: My Stockholm syndrome with biofilms Hans-Curt Flemming PII:

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https://doi.org/10.1016/j.watres.2020.115576

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Received Date: 23 August 2019 Revised Date:

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Please cite this article as: Flemming, H.-C., Biofouling and me: My Stockholm syndrome with biofilms, Water Research (2020), doi: https://doi.org/10.1016/j.watres.2020.115576. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Ltd.

1

Biofouling and Me: My Stockholm Syndrome with Biofilms

2

Hans-Curt Flemming1,2,3,4

3

1

Water Academy, Schloss-Strasse 40, D-88045 Friedrichshafen, Germany

4

2

Singapore Centre for Environmental Life Sciences Engineering (SCELSE), 60 Nanyang Drive, Singapore 637551

5 6

3

5, 45141 Essen, Germany

7 8

Biofilm Centre, Faculty of Chemistry, University of Duisburg-Essen, Universitätsstr.

4

IWW Water Centre, Moritzstrasse 26, 45476 Muelheim, Germany

9 10

Keywords: Biofouling, Biofilms, Anti-Fouling, Holistic Approach

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Stockholm syndrome: psychological response wherein a captive begins to identify

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closely with his or her captors, as well as with their agenda and demands.

13 14

Abstract

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Biofouling is the undesired deposition and growth of microorganisms on surfaces,

16

forming biofilms. The definition is subjective and operational: not every biofilm

17

causes biofouling - only if a given a subjective “threshold of interference” is

18

exceeded, biofilms cause technical or medical problems. These range from the

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formation of slime layers on ship hulls or in pipelines, which increase friction

20

resistance, to separation membranes, on which biofilms increase hydraulic

21

resistance, to heat exchangers where they interfere with heat transport to

22

contamination of treated water by eroded biofilm cells which may comprise

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hygienically relevant microorganisms, and, most dangerous, to biofilms on implants

24

and catheters which can cause persistent infections. The largest fraction of anti1

25

fouling research, usually in short-term experiments, is focused on prevention or

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limiting primary microbial adhesion. Intuitively, this appears only logical, but turns

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out mostly hopeless. This is because in technical systems with open access for

28

microorganisms, all surfaces are colonized sooner or later which explains the very

29

limited success of that research. As a result, the use of biocides remains the major

30

tool to fight persistent biofilms. However, this is costly in terms of biocides, it

31

stresses working materials, causes off-time and environmental damage and it

32

usually leaves large parts of biofilms in place, ready for regrowth. In order to really

33

solve biofouling problems, it is necessary to learn how to live with biofilms and

34

mitigate their detrimental effects. This requires rather an integrated strategy than

35

aiming to invent “one-shot” solutions. In this context, it helps understand the biofilm

36

way of life as a natural phenomenon. Biofilms are the oldest, most successful and

37

most widely distributed form of life on earth, existing even in extreme environments

38

and being highly resilient. Microorganisms in biofilms live in a self-produced matrix

39

of extracellular polymeric substances (EPS) which allows them to develop

40

emerging properties such as enhanced nutrient acquisition, synergistic

41

microconsortia, enhanced tolerance to biocides and antibiotics, intense intercellular

42

communication and cooperation. Transiently immobilized, biofilm organisms turn

43

their matrix into an external digestion system by retaining complexed exoenzymes

44

in the matrix. Biofilmsgrow even on traces of any biodegradable material, therefore,

45

an effective anti-fouling strategy comprises to keep the system low in nutrients

46

(good housekeeping), employing low-fouling, easy-to-clean surfaces, monitoring of

47

biofilm development, allowing for early intervention, and acknowledging that

48

cleaning can be more important than trying to kill biofilms, because cleaning does

49

not cut the nutrient supply of survivors and dead biomass serves as an additional

50

carbon source for “cannibalizing” survivors, supporting rapid aftergrowth. An 2

51

integrated concept is presented as the result of a long journey of the author through

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biofouling problems.

53 54

1. How it started

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After my Ph. D. at the Max-Planck-Institute for Immunobiology in Freiburg, Germany,

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I was hired in April 1978 at the Institute for Sanitary Engineering, Water Quality and

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Solid Waste Management of the University of Stuttgart in the Department of

58

Chemistry. My project was about the microbial contamination of pure and ultrapure

59

water upon treatment with ion exchangers (Flemming, 1987). The problem was

60

termed “biofouling” and caused considerable problems. Microbial contamination

61

turned out to be the cause for occasional hygienic objections in drinking and brewing

62

water, water for pharmaceutical use, and for failures of electronic microchips, who

63

had to be rinsed with ultrapure water during the process of printing electrical circuits.

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Bacteria lead to shortcuts and painful loss of finished chips as the cells would act as

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conductive particles due to their water content. This limited the use of ion exchangers

66

for production of ultrapure water as an alternative to much costlier distillation

67

(Flemming, 1987).

68

In hindsight, it was obvious to look at the surfaces as sources for the contaminations,

69

but at that time (late 70’ies/early 80´ies), scientific approaches concentrated rather on

70

the water phase. Sure enough, it turned out that ion exchanger resin beds hosted

71

“nests” of microbial colonies on ion resin surfaces, and it could be demonstrated that

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they were recalcitrant against disinfection, led to microbial regrowth and recurring

73

contamination of the treated water (Flemming, 1981; 1987). Great hope was put on

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the effect of the bacteriostatic effect of traces of silver ions, as provided, e.g., by

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silver-coated resins. To my great disappointment, silver coating did not help to solve 3

76

the problem – after few weeks, silver-tolerant populations emerged (Flemming,

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1982). But the silver resin beads, generated by loading the cation exchanger with

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silver ions and reducing the silver by ascorbic acid, and the result looked very

79

beautiful. I took my children to the lab and they were mystified by “silver making”, but

80

later, excessive consumption of silver salt without valid justification was critizised.

81

Another alternative to distillation was the employment of reverse osmosis technology.

82

But membrane technology also experienced biofouling, its “Achilles heel” (Flemming

83

et al., 1997). “Biofouling” was defined as “development of a biofilm consisting of

84

microorganisms and their products.“ (Characklis and Cooksey, 1983), i.e., the

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unwanted deposition and growth of microorganisms on surfaces. Thus, biofouling is

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an effect of biofilm presence and growth – clearly a biofilm problem. It was just one of

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four types of fouling. The others were mineral fouling (scaling), organic fouling and

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particle fouling (Epstein, 1981), and usually, more than one of them was involved in

89

fouling cases.

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Microbial biofouling is observed in a very wide spectrum of technical and medical

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fields and causes very diverse problems. Table 1 provides an idea of the dimensions.

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Table 1: Some fields affected by biofouling

93 94

2. The costs of biofouling

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The funding for my research was triggered by the costly damage caused by

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biofouling. However, although being a common phenomenon in many different fields

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(see Table 1), there is very little quantitative data about the overall costs. Admittedly,

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it is difficult to assess the global biofouling-related costs, because they are caused by

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a number of various factors: from interference with process performance, decrease of 4

100

product quality and quantity, to material damage by microbial attack which even can

101

include minerals, organic polymers (Flemming, 2010) or metals (“microbially

102

influenced corrosion”, MIC (Little and Lee, 2014)), preventive overdosing of biocides

103

and cleaners, and finally, most expensive, interruptions of production processes and

104

shortened life-time of plant components due to extended cleaning. An additional

105

matter of expense is caused by the treatment of wastewater contaminated by anti-

106

fouling chemicals. Biofilms cause monumental costs in the health system,

107

considering that about 80 % of human bacterial infections are biofilm-associated

108

(Römling and Balsalobre, 2012).

109

But looking at the economically healthy anti-fouling industry which offerseverything

110

from anti-fouling surfaces and materials, biocides, cleaners and consulting services,

111

illuminates the economical dimension – this market is worth billions of dollars

112

annually worldwide. Biofouling generates a safe and con business because biofilms

113

cannot be erased once and forever.

114

Three examples may illustrate the economic dimensions of biofouling:

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(i): Membrane biofouling.

116

The costs of biofouling have been estimated in the membrane treatment system at

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Water Factory 21, Orange County, to 30 % of the operating costs, at that time about

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$750.000 per year (Ridgway and Flemming, 1996) - this rate has not much changed

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since (Flemming, 2011). The estimate considered not only on the costs for

120

membrane cleaning itself and labour costs but also down-time during cleaning, pre-

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treatment costs, including biocides and other additives, an increased energy demand

122

due to higher transmembrane and feed-brine hydrodynamic resistance, and

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shortened lifetime of the membranes. Reportedly, to avoid excessive cleaning,

124

biofouled membrane systems are frequently operated outside the manufacturer´s 5

125

warrantee condition of less than 15 % increase of the normalized pressure drop

126

increase over the total installation between cleanings (Vrouwenvelder et al., 2011).

127

Interestingly, it is the EPS which contribute to the hydrodynamic effects, not the cells

128

embedded in the biofilm; they generate the bulk of the hydrodynamic resistance

129

(Vrouwenvelder et al., 2016; Derlon et al., 2016). This indicates that killing the cells

130

alone will not help sanitizing membrane fouling biofilms. In a case study the author

131

was involved in, treatment of seawater for injection into oilfields for replacement of

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the oil was performed by nanofiltration membranes. The client reported: “Due to

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biofouling, membrane life is reduced from three to one year, so over the life of the

134

plant the cost of membrane replacement will be increased by a factor of 3. If it is

135

taken into account that each membrane costs 2500 $ and each plant has around 700

136

membranes, one can easily calculate a yearly investment cost of 1.75 million instead

137

of 0.58 million. That means an extra cost of 1.17 Million a year just for membrane

138

replacement, but this can easily increase significantly if man hours involved in

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replacements, filters and piping replacement cost, fees paid to the client for

140

downtimes, loss of water quality and further factors are taken into account”. Such

141

cost assessments, even if crude, reflect how complex and essentially arbitrary any

142

numbers are, but they show one thing for certain: that they are high. Further but

143

rarely acknowledged biofouling-related costs arise from interrupted water production,

144

missing contractual requirements.

145

(ii): Paper production

146

In paper production, biofouling can cause substantial problems in production and

147

paper quality (Flemming et al., 2013 b). Losses are arise from of a number of

148

complex scenarios including direct damage by biofouling (holes, breaks, malodor,

149

and microbial contamination), the cost of controlling biofouling (biocides, dispersants, 6

150

cleaners, etc.), downtime during slime-related cleaning, and eventually the loss of

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product quantity and/or quality. It has been estimated that US $1–2.5 per tonne of

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produced paper are spent on antimicrobials, biodispersants, and cleaning chemicals

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during production (Nalco, unpublished). Contaminated raw materials and additives

154

contribute to biofouling damage. Paper is made primarily from cellulose fibers, but it

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also contains various amounts of a variety of additives, eg., calcium carbonate or

156

titanium dioxide. Microbial contamination can lead to graying of mineral pigment

157

slurries and to the formation of malodorous metabolites that cannot be sanitized. This

158

has been observed in tanks in railroad wagons after extended stay and can amount,

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according to the volume of the tank, to losses of several US $ 10,000 per tank of ca.

160

100 m3. Deficient products or batches of microbially deteriorated additives, such as

161

starch or pigments, can account for losses in the range of several US $10,000 per

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batch. The costs for preserving mineral pigments against microbial contamination

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range between US $2–3 per tonne. The practical experience of the authors

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(Flemming et al., 2013 b) has shown that microbial spoilage and degradation of

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dispersants can lead to viscosity changes, which may result in the plugging of jet

166

coaters or scratches in the coating when coating agglomerates become trapped on

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the coating blade. Microbial spoilage and degradation of binders can have a negative

168

impact on product quality. Although paper makers understand the economic benefits

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associated with deposit control, they tend to overlook spoilage of additives and fibers

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because it is often difficult to detect directly. Ignoring these processes can be costly

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and environmentally risky and can present a direct safety hazard, for example, when

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explosive gases such as H2 or methane, or toxic ones such as H2S are, generated by

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microbial activity and have led reportedly to accidents (Flemming et al., 2013 b).

7

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The biggest cost factors associated with slime formation in paper production are downtime

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and cleaning costs. Much of the cost is the result of breakdowns caused by lumps of slime

176

dropping onto the moving screen, on which the water is separated from the pulp, and causing

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holes (see above). A single breaktown can cost between US $ 2,000 and 10,000, depending

178

on the size of the plant, the process and the quality of the paper. . Such events can

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considerably reduce the operational efficiency of the plant if they occur once or more times

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daily, although not all breaks are caused by biofouling, but 1–2 out of 5 cases are probably

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related to microbial biomass. It is obvious that the overall costs from biofouling tend to be

182

underestimated massively.

183 184

(iii) Heat exchangers

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In heat exchangers, the decrease of efficacy of heat transfer is the first aspect of

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biofouling-related costs and contributes to the “fouling factor” (Characklis et al., 1990;

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Melo and Flemming, 2010; Müller-Steinhagen et al., 2011). Biofouling – very

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conservatively assumed – accounts for about 20 % of overall fouling in energy

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generation. In order to match the fouling factor, preventive extended dimensioning of

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heat exchanger plants is a common practice. Thus, biofouling directly increases the

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capital costs of, e.g., a power plant (Murthy and Venkatesan, 2009). In power plants

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around the world, thousands of tons of chlorine and other biocides as well as

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cleaners are spent each day to combat biofilms, which amounts to high values in

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terms of biocide and wastewater treatment costs (Cloete, 2003). Again, down time for

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cleaning causing loss of production and labour costs adds on a large share of costs.

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Furthermore, it should be considered that the efficacy of biocides can be significantly

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compromised by abiotic material such as clay particles in biofilms (Pereira et al.,

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2000). 8

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Treatment of wastewater contaminated with antifouling additives represents an

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emerging cost factor as the release of biocides is increasingly restricted and will

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require more effort for elimination – a problem which comes further into focus in

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Europe after new EU guidelines which limit the biocide content in effluents come into

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action (Flemming and Greenhalgh, 2009; Pereira and Ankjaergaard, 2009; Cheyne,

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2010). What clearly makes more sense is putting more effort in prevention of

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biofouling by advanced strategies.

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3. Trapped in biofilms

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It was more than obvious: biofouling is a biofilm problem, and solutions would require

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in-depth knowledge about biofilms. On this journey, I developed a deep appreciation,

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fascination and admiration of this form of microbial life – a process metaphorically

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comparable to the Stockholm-syndrome.

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In August 1986, I attended the 3rd International Symposium on Microbial Ecology

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(ISME) in Ljubliana. That was a true awakening. Mesmerized, I listened to the

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presentations of charismatic researchers such as Kevin Marshall, Bill Costerton, Bill

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Characklis, David White and others about biofilms. I saw Gill Geesey and Mark van

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Loosdrecht mounting their posters on the extracellular polymeric substances (EPS)

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and activated sludge. I sat in lectures with goose bumps on the skin on my spine

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because I was so excited getting such an incredibly rich field of research spread out

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right under my eyes. Costerton claimed that the vast majority of microorganisms on

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earth actually lives in biofilms (Costerton et al., 1987). What a field of research! This

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conference changed my life: suddenly the dimension of biofilms unfolded to me as

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the general way in which microorganisms organized their life. Decades later, my

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friend Stefan Wuertz and I noticed that no data at all existed supporting Costerton´s 9

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claim. Nevertheless, it was cited hundreds of times, including in my own papers. We

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challenged that claim and could eventually confirm his intuition, although not his

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“99%” (Flemming and Wuertz, 2019). But by that time, almost no one in Germany

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was interested in biofilms, except Peter Wilderer (Rubio and Wilderer, 1987) and

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Martin Exner who approached it from a hygienic perspective (Exner et al., 1982).

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Biofouling on ion exchangers was just one of the manifestations in the huge realm of

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biofilms, and I got a glimpse of a bigger picture, a very much bigger picture. When I

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returned to my lab from this conference, I told my group that biofilms is what will be

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our future field of research. Which it has remained ever since.

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One of the keys to understanding the biofilm mode of life is the role of EPS. They are

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the “house of biofilm cells” in which they unfold their unique properties (Flemming

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and Wingender, 2010). As highly hydrated biopolymers such as polysaccharides,

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proteins, lipids, nucleic acids etc., they provide the mechanical stability which keeps

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biofilm cells in close proximity to each other for extended periods of time and allow

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synergistic interactions, e.g., the formation of microconsortia, stabilized the matrix.

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However, they are still considered as the “dark matter of biofilms” (Flemming, 2016)

240

and much of their properties and dynamics remain to be explored (Seviour et al.,

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2018). Extracellular enzymes are retained in the matrix by complexation, turning

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biofilms into external digestion systems which enables them to even degrade solids.

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They are the key players in the global self-cleaning system of the planet. Different

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physiological interactions lead to steep gradients in pH-value, oxygen concentration,

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redox potential etc. which provides habitat heterogeneity and supports biodiversity

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within only few micrometres of distance. Furthermore, life in biofilms supports nutrient

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acquisition by sorption of nutrients from the environment, and for intercellular

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communication in close proximity. Last not least, a biofilm represents a huge genetic

10

249

archive accessible for horizontal gene transfer. Thus, “biofilms are habitats of

250

conditions markedly different from those of the ambient environment and drive

251

microbial cells to effect functions not possible alone or outside biofilms” (Corning,

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2002). Such phenomena are termed as “emergent properties”, as they cannot be

253

predicted from the behaviour of single cells (Flemming et al., 2016). This is why the

254

matrix was metaphorically termed “The Perfect Slime” (Flemming, 2016). It is clear

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now that all global biogeochemical processes are driven by biofilms (Flemming and

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Wuertz, 2019). In fact, most of the active microorganisms on earth live in biofilms,

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driving biogeochemical processes, environmental self-purification and production of

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pristine groundwater at global dimensions. Interestingly, they connect processes in

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the deep subsurface with those on the on earth surface (Flemming and Wuertz,

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2019). Biofilms shape their habitats by interacting with it, be it by dissolving or

261

precipitation of minerals, by changing pH-value, redox potential, oxygen

262

concentration of salinity, and they effectively shape their habitats. The emerging

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properties of biofilms elevate them into the class of collective forms of life such as

264

forests, coral reefs or bee hives (Flemming et al., 2016). Fig. 1 schematically

265

presents some of the properties emerging from living in biofilms.

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Figure 1: Emergent properties of biofilms, leading to habitat formation (from

268

Flemming et al., 2016, with permission)

269 270

One particular emergent property of biofilms should be pointed out which

271

metaphorically was described as “The Biofilm as a Fortress” (Flemming et al., 2016).

272

This term characterizes the remarkable resilience of biofilms to antimicrobials of

273

chemical, physical and biological kinds. The terms employed in this context are 11

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“resistance” and “tolerance”, referring to an enhanced ability of an organism to

275

survive exposure to compounds that are lethal to susceptible organisms. Resistance

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denotes a genetic, heritable characteristic that is acquired either by mutation or by

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gene exchange and that remains even when biofilm cells are dispersed (Olsen,

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2015). By contrast, the term tolerance is used to denote a characteristic that is

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specific to biofilms, which is lost upon dispersal to free-living bacterial cells (e.g.,

280

tolerance to silver ions (Königs et al., 2015, Thuptimdang et al., 2015; Brauner et al.,

281

2016).

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Tolerance in biofilms can be a product both of the properties of the biofilm matrix, of

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the slow growth that can occur in biofilms, or retarding/inactivation of antimicrobials,

284

or the presence of particles (Vieira et al., 1995). Intuitively, it seems plausible that the

285

EPS matrix represents a diffusion barrier. However, antimicrobials which do not

286

interact with EPS molecules have been shown to diffuse through biofilms as easily as

287

through water (Oubekka et al., 2012), which is simple to understand, considering that

288

the biofilm matrix consists of 95-99 % of water (Flemming and Wingender, 2010).

289

The diffusion barrier alone is not nearly effective enough to account for the reduced

290

susceptibility of biofilms to antibiotics – it would only slow down the transport of the

291

antibiotics and reaching the cells would be just a matter of extended diffusion time.

292

Antimicrobial substances diffusing through the biofilm can react with EPS

293

components of the matrix by binding or by enzymatic degradation, which substantially

294

quenches the antimicrobial activity of these compounds (Billings et al., 2015) in a

295

form of inhibition known as reaction-diffusion inhibition (Stewart et al. 2016). The

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reaction component can involve chelation by complex formation and enzymatic

297

degradation, or even sacrificial reaction of EPS (for example, with oxidizing

298

disinfectants, (Oubekka et al., 2015). This results in sublethal antibiotic

12

299

concentrations and survival of cells in the depth of the biofilm, with an increased risk

300

of development of genetically based resistance.

301

Biofilms contain substantial numbers of cells in stationary phase, which are less

302

susceptible to the many antimicrobials that rely on the metabolism of bacterial cell for

303

their activities (Amato et al., 2014). Indeed, for biofilm cells in stationary phase, at

304

least 1% of bacterial cells become tolerant to antibiotics (Maisonneuve et al., 2014).

305

Over time, a greater number of cells in the biofilm enter the stationary phase. Slow

306

growth rate and dormancy (“playing dead”) have long been recognized as a means of

307

survival for bacteria in biofilms exposed to antimicrobials. As a stress response to

308

biocides, antibiotics, physical or chemical stressors, microorganisms can enter a

309

state of dormancy in which they do not grow on media usually employed to their

310

detection (Oliver, 2005). This behavior has been termed “viable-but-non-culturable”

311

(VBNC) and is related to the phenomenon of persisters (Kim et al., 2018). Figure 2

312

depicts hypothetical mechanisms of biofilm resilience (Flemming et al., 2016, with

313

permission).

314 315

Figure 2: Tolerance and resistance of biofilm organisms (Flemming et al., 2016, with

316

permission)

317 318

4. Measures against biofouling

319

Practically all fields suffering from biofouling have developed their own approaches to

320

handle the problem, while there is not much lateral exchange and learning about the

321

strategies or adoption of concepts. Antifouling strategies in food, beverage,

322

pharmaceutical and microelectronics industries or ships (Cole, 1998; Verran and 13

323

Jones, 2000; Wirtanen and Salo, 2003; Hellio et al., 2009) are considerably more

324

sophisticated than, e.g., those of power generation, automobile or paint production.

325

Biofilm formation begins with primary adhesion of microorganisms to interfaces. For

326

solid surfaces, the fascinating process of surface sensing and the effect of adhesion

327

to the cell and its physiology recently has been investigated in depth. Attachment to

328

surfaces deforms the cells, activates mechano-sensitive channels and triggers

329

“surface-programmed growth” (Carniello et al., 2018; Berne et al., 2018; Ren et al.,

330

2018).

331

By far the largest body of literature is dedicated to prevention or mitigation of primary

332

adhesion. Table 2 lists a few of them, pointing out their limitations. All of them have

333

the general problem that the gap between proof of principle and industrial application

334

very rarely has been bridged, nor the aspect of costs. This is one of the reasons why

335

so very few of them have made it into practical antifouling application.

336

But there are more general limitations of these approaches. One is the usually short

337

experimental period. Many studies are carried out in 96 well plates and maximally for

338

96 hours, often with pure or very artificially mixed cultures, rarely representative for

339

environments as existing in practice. Furthermore, the deposition of abiotic material

340

also contributes to overall fouling, but is very rarely taken into consideration. This is

341

the case, e.g., in drinking and wastewater systems, in technical water systems or in

342

the marine environment. Here, a plethora of mixed species is ready to colonize

343

surfaces, instead of Pseudomonas aeruginosa or Escherichia coli, the organisms

344

most frequently employed in studies, with the papers usually concluding with the

345

word “promising”. These single or mixed populations behave differently and they

346

respond to any treatment by selection for specialists who are not repelled. Long-term

347

stability and efficacy of anti-fouling approaches is also a crucial aspect of successful 14

348

anti-fouling and rarely considered in the studies as listed in Table 2. Nevertheless,

349

the list reflects creativity and inspiring diversity of approaches. Particularly interesting

350

are those which are adopted from nature (Bixler and Bushan, 2012), e.g., by

351

jewelweed (Impatiens carpensis), or red seaweed (Delisea pulchra). However, only

352

the “lotus effect” as observed in Nelumbo nucifera (Barthlott and Nienhuis, 1977) has

353

made it out of the laboratory to broader technical applications, but not submerged in

354

water, because it only works on hydrophobicity which requires both water and gas

355

phase.

356 357

Table 2: Innovative “dream” approaches to prevent biofouling

358 359

4.1 Detection of biofouling

360

A crucial point in any anti-fouling strategy is the timely detection of biofouling. Most

361

systems are inaccessible for surface inspection. Commonly, biofouling is diagnosed

362

when process or product parameters indicate problems which cannot be easily

363

attributed to normal physical, technical or chemical reasons (Flemming, 2002, 2011).

364

Equally common practice is to take water samples at points of use of the water or

365

from products and determine the number of planktonic bacteria, preferably employing

366

cultivation methods. The results are usually misleading and leads to piles of data

367

without sense. Reason is that the number of cells in water does not give any

368

information about location or extent of the fouled area, as the release of biofilm cells

369

to water is random, with peaks caused by detached patches and irregular erosion of

370

single cells.

15

371

However, if water samples are taken systematically along a water system, they allow

372

to localize hot spots which then can be addressed directly. In a practical example of

373

microbial contamination of water, samples were taken upstream until the entry point

374

into the system. In this case, elevated counts were found up to the ion exchanger,

375

while further upstream, the numbers were significantly lower. This allowed to identify

376

the ion exchanger as the source of contamination which then had to be cleaned.

377

Taking samples from accessible surfaces (preferably from defined areas) is always a

378

good idea. Such samples can be analysed in the laboratory. Determination of the

379

content of protein, polysaccharides, DNA, ATP, and microbial cells allows further

380

characterization of the fouling layer and the amount of biomass (compiled by Manalo

381

and Nishijima, 2019). However, although I dedicated substantial parts of my

382

research to EPS (e.g., Flemming and Wingender, 2010; Flemming, 2016), it still

383

frustrates me how little practically useful information such data provided, and that no

384

useful strategies to combat or foster biofilms could be developed using the present

385

information on EPS.

386

It is important not to rely on numbers acquired by cultivation methods and counting

387

colony forming units (cfu), because less than 1 % of all bacteria actually present in

388

the sample can be cultivated, particularly those in the depth of biofilms. However, the

389

non-growing cells are part of the overall biomass and can contribute to water

390

contamination and to physical effects of biofilms, e.g., hydrodynamic resistance.

391

Therefore, it is a good idea to determine the total microbial cell numbers (TC), e.g.,

392

by fluorescence microscopy. Interestingly, the comparison between cfu and TC gives

393

information about the nutrient status of a system. In oligotrophic waters such as

394

drinking or purified water, the ratio cfu:TC is below 1:1,000. If the ratio is higher, it

395

indicates the presence of nutrients. Such information can be very important in order 16

396

to understand the occurrence of elevated cell numbers and to search for possible

397

nutrient sources. This is facilitated by the increasing employment of flow cytometry in

398

drinking water (Prest et al., 2016).

399

If membrane modules are irreversibly fouled, an autopsy can reveal biofouling. Good

400

care is advised when opening a fouled module. It is possible that not only bacteria

401

but also fungi may be involved (Fig. 3). Spreading of spores has been observed,

402

contaminating two entire microbiological laboratories and representing a health

403

hazard, and as it happened to us, it made us very unpopular because the spores

404

contaminated most microbal cultures in those laboratories. Since then, we did

405

membrane autopsies under controlled, safe conditions.

406 407

Figure 3: Fungal biofouling on an irreversibly fouled membrane, employed in river

408

water purification (coutesy of G. Schaule)

409 410

4.2 Sanitation of biofouling – killing is not cleaning

411

Once biofouling has been recognized, the common response is called “disinfection”.

412

However, even if the microorganisms are killed, cleaning is much more important,

413

i.e., removing the biomass because fouling of membranes or heat exchangers not is

414

not caused by the physiological activity of the cells, but by the biomass. Killing is not

415

cleaning, as remaining and subsequent cells grow on expense of the biomass

416

(Flemming, 2002).

417

Cleaning requires to overcome biofilm adhesion and cohesion (Körstgens et al.,

418

2001; Fabbri and Stoodley, 2016). The forces which are responsible are provided by

419

the EPS molecules and weak in nature. They comprise hydrogen bonding, weak ionic 17

420

interactions, hydrophobic and van der Waals interactions and entanglement (Wloka

421

et al., 2004; Flemming and Wingender, 2010). Surface active substances mainly

422

address hydrophobic and van der Waals interactions, complexing agents act on ionic

423

bonds. Hydrogen bonds can be addressed by so-called chaotropic agents such as

424

ureay, tetramethyl urea and others which interfere with the shell of water molecules

425

surrounding the biomolecules (Mayer et al., 1999). The contribution of entanglement

426

to matrix stability can be weakened by either oxidizing agents or enzymes, shortening

427

the length of the polymer chains. In food industries, enzyme applications have been

428

studied in detail (Lequette et al., 2010; Cordeiro and Werner, 2011; Cordeiro et al.,

429

2011). The second requirement for successful cleaning is to remove the weakened

430

matrix by shear forces, usually, by removing it using increasing fluid velocity or

431

applying pressurized air-water flows/jets.

432

Hydraulic cleaning is the most commonly used physical method. Water is flushed

433

through the system in forward or backward direction to remove the accumulated (and

434

weakened) biomass and other foulants. In membrane systems, forward flushing can

435

cause further biofouling problems as the biomass accumulated in the lead membrane

436

is pushed to the ones downstream, where they may lead to clogging and to further

437

biofilm formation. Due to this reason, some plants perform a backwash by reversing

438

the module, thereby reducing the chance of spreading the biomass to all the adjacent

439

membrane modules. Pneumatic cleaning refers to the use of air or gas mixed with

440

water for flushing (air-water flushing). A series of experiments shows promising

441

results on pilot scale for the use of air/water flushing (Wibisono et al., 2015; Bucs et

442

al., 2018). Employment of CO2 dissolved in excess in water has proven to restore

443

initial hydraulic resistance as well as visible reduction in biofouling (Ngene et al.,

444

2010).

18

445

Biological dispersal has been addressed for biofilm removal. It is very clear that the

446

biofilm matrix is not a prison to its inhabitants. Biofilm dispersal is regulated by

447

processes equally complex as bacterial adhesion. Enzymes are the means to leave

448

the matrix (McDougald et al., 2012; Petrova and Sauer, 2016). However, none of

449

these enzymes disperse entire biofilms – they just generate holes in the matrix big

450

enough some community members to escape. Neither single enzymes or their

451

mixtures are capable to address the huge variety of EPS molecules (Brisou, 1995)

452

and disperse biofilms completely. Therefore, all kinds of mixtures are used,

453

particularly in paper (Flemming et al., 2013 b) and food industries (Simões et al.,

454

2010). However, enzyme application inevitably leads to selective pressure over time,

455

favouring organisms producing EPS varieties insensitive to the enzymes. What also

456

limits their efficacy is the fact that the enzymes themselves are rapidly degraded by

457

extracellular proteases.

458

The use of signalling molecules (quorum sensing, QS) for biofilm dispersion has

459

been suggested and is still intensively investigated (Davies, 2011; Barraud et al.,

460

2009; Brackman and Coenye, 2015; Siddiqui et al., 2015; Lee et al., 2018; Katebian

461

et al., 2016; Oh et al., 2018). Again, these molecules are relatively specific,

462

biodegradable, exert selection pressure in favour to non-responsive members of

463

mixed biofilm populations and of doubtful success on a long term. Application and

464

required quantities also pose problems. Long-term success in practice has not been

465

reported yet (Vrouwenvelder, pers. comm.).

466

In practice, cleaning of biofilms from surfaces appears more an art than a science,

467

dominated by trial-and-error rather than based by the scarce systematic research

468

(Mayer et al., 1999; Körstgens et al., 2001). This is surprising considering that

469

cleaning is such a crucial component of anti-fouling measures. 19

470 471

4.3 How to live with biofilms – a holistic approach

472

As mentioned before, most microorganisms on earth actually live in biofilms and that

473

they belong to the oldest and most successful form of life on this planet. They have

474

been exposed to every possible stress during billions of years since they exist and

475

are thriving. From that point of view, it appears obvious that there is no “silver bullet”

476

to eliminate them. Rather, it is worthwhile to learn how to live with biofilms. Therefore,

477

in all anti-fouling efforts, it must be kept in mind that biofilms have developed versatile

478

and multiple defence strategies against a multitude of stresses, including those, e.g.,

479

by toxic metals, irradiation, antibiotics and host immune systems over billions of

480

years. Thus, an easy and lasting victory over biofouling cannot be expected – only an

481

extension of the period of time in which biofilms do not cause problems. A good

482

metaphor is, that teeth cannot be cleaned once and forever.

483

Intuitively, biofouling is considered a kind of a “disease” of the system, and

484

countermeasures mirror a medical paradigm: kill the “pathogen” and the system will

485

recover. The method of choice is to apply biocides in order to obtain a “disinfection”.

486

This remains the most frequently taken road and supports a healthy biocide industry

487

(Flemming, 2011). If repeated on a regular basis, over time damage of the system

488

occurs, e.g., by chemically stressing separation membranes or promoting corrosion.

489

As a consequence, anti-fouling success is time dependent and not permanent. The

490

temporal requirements range from hours to days (e.g., for removable catheters, food,

491

beverage and pharmaceutical industry, to months and years (e.g., desalination

492

plants, membrane systems, steam condensers, ship hulls or environmental sensors).

493

This makes it difficult to extrapolate from short-term experimental results to long-term

494

efficacy. 20

495

Biofilms develop on all surfaces, provided sufficient humidity and nutrients are

496

present. Hovever, not all technical systems suffer from biofouling. Many live with the

497

biofilms and without problems. Biofouling is strictly operationally defined: it occurs

498

when the effect of biofilm exceeds an arbitrary threshold of interference; in

499

membrane systems or heat exchangers, more than 15 - 20 % loss in efficacy exceed

500

this threshold. The situation is depicted in Fig. 4.

501 502

Figure 4: Development of biofilms and the “Threshold of interference” above which

503

biofouling is reported. ∆ = Parameter for biofilm effect, e.g., hydraulic or friction

504

resistance, thickness etc. Inset: primary adhesion. (from Flemming, 2011, with

505

permission)

506 507

Any measures which allow to lower the level of biofilm effects below the threshold of

508

interference will help to live with biofilms. On that background, it is very important to

509

perform module autopsies of systems which do not suffer from biofouling in order to

510

size the tolerable extent of biofilm growth, below the threshold of interference. This

511

illustrates that biofouling cannot be prevented with single-shot approaches but rather

512

by holistic strategies. One way is to design systems more tolerant to biofouling; this is

513

implicitly adopted in preventive oversizing, e.g., membrane or heat exchanger

514

systems. An elegant way to overcome the hydraulic resistance of biofilms on filtration

515

membranes, which is essentially caused by compression of the EPS molecules

516

(Dreszer et al., 2013; Derlon et al., 2014) is application of very low pressure, e.g., in

517

gravity driven membrane filtration (Pronk et al., 2019). This version of “living with

518

biofilms” does not only suffer much less from biofouling but also provides flux

519

stabilisation and improved permeate quality. 21

520 521

4.3.1 Biofouling potential

522

A first step is the determination of the biofouling potential in order to recognize

523

biofouling risk. In water treatment systems, the quality of the feed water is a crucial

524

factor. Manalo and Nishijima (2019) elaborated this for RO systems. To characterize

525

the fouling potential, the most important parameters are the total dissolved solid

526

(TdS) contents and the organic load in terms of total organic carbon (TOC). The

527

biodegradable proportion of TOC will support the growth of biomass. Manufacturers

528

suggest pretreatment of feed water when TOC exceeds 3 mg/L (DOW, 2010). Humic

529

components are not readily biodegradable but support slow growth of

530

microorganisms, contributing to biofouling on a long term. They absorb UV radiation,

531

therefore, determination of UV254 nm is suggested for assessment the fouling potential

532

(Sim et al., 2018). For detection of the microbial load, determination of TC is

533

recommended rather than enumeration of cfu. The silt density index (SDI) was found

534

to be of only limited use as a predictor of the biofouling potential because it is too

535

sensitive to other factors such as pH-value, membrane characteristics and turbidity of

536

water. Good feed water quality for membrane desalination is defined by membrane

537

manufacturers as water with a turbidity lower than one Nephelometric Turbidity Unit

538

(NTU), silt density index (SDI) < 3, oil and grease < 1 mg L-1. If these requirements

539

are not met, the water requires pretreatment (Bucs et al., 2018), usually by filtration.

540 541

4.3.2 Good housekeeping and nutrient limitation

542

Achieving and maintaining low bacterial numbers in the water phase and a clean

543

system is part of a good housekeeping regime. This includes particularly the

544

quantification and elimination of nutrients as microorganisms are particles which can 22

545

multiply on the expense of anything which is biodegradable – this belongs to the

546

biofouling potential. Therefore, nutrient limitation is a useful tool for mitigating

547

biofouling problems. Nutrients are not only provided by the water phase but can also

548

leach from polymeric materials, e.g., biodegradable plasticizers, anti-statics and other

549

additives; they also can origin from sealing and fitting components. Material selection

550

is one of the key points in maintaining low biofouling in drinking water systems or

551

household installations (Flemming et al., 2013 a). In some cases, disinfection has

552

contributed to biofouling by partially oxidizing humic substances and make them

553

biodegradable (LeChevallier, 1999).

554

In biofouled systems, the same processes happen as in a biofilter: biofilms convert

555

nutrients into metabolites and biomass. Biofouling can be considered a biofilter in the

556

wrong place. A biofilter in the right place, i.e., ahead of the system, would remove

557

organic carbon and, thus, limiting biofilm growth behind the biofilter. This has first

558

been demonstrated by Griebe and Flemming (1996) and was successfully applied in

559

membrane and cooling systems (e.g., Meesters et al., 2003; Gule et al., 2016;

560

Moreira et al., 2016; Manalo and Nishijima, 2019) and expanded by phosphate

561

(Vrouwenvelder et al., 2010; Bucs et al., 2014; Kim et al., 2014) and nitrogen

562

limitation (Hwang et al., 2010) ahead of membrane systems.

563

A comprehensive approach is the application of the Water Safety Plan (WSP)

564

principles (WHO 2010). The big advantage is that this embraces the entire system,

565

including all raw materials, installations and processes. The procedure appears

566

laborious but is well established and very successful.

567 568 569 23

570

4.3.3. Low adhesion/antifouling, easy-to-clean surfaces.

571

The surface energy of the substratum is one of the most relevant physico-chemical

572

parameters influencing settlement and adhesion strength of fouling (Lejars et al.,

573

2012). Antifouling strategies employing coatings which cannot prevent, but delay

574

biofilm formation (Bucs et al., 2018; Giessler et al., 2006). Such coatings fall into

575

three main categories (Lejars et al., 2012; Swain, 2017):

576

i)

chemically active coatings, which act on marine organisms by inhibiting or

577

limiting their settlement, using chemically active compounds releasing them

578

in a controlled way, usually as self-polishing copolymer coatings, based on

579

aceylic or methacrylic copolymers, or releasing biocides.

580

ii)

release of settled organisms without involving chemical reactions

581 582 583

nontoxic coatings which inhibit the settlement of organisms or enhance the

iii)

Engineered microtopographical surfaces (which are particularly sensitive to abiotic fouling and mechanical stress)

584

A comprehensive overview of the most common silicone-containing and fluorine-

585

based fouling release coatings is provided by Lejars et al. (2012). In medical

586

environments, hydrogel silicones have been successfully employed (Peppas et al.,

587

2000). In every case, ageing of coatings can represent a significant problem

588

(Sánchez et al., 2009).

589

These coatings, however, have some limitations, as already mentioned in Table 2.

590

They are particularly susceptible to fouling during stagnation periods; some of them

591

cast doubts over their long-term durability, adhesion to support and stability towards

592

water and the impact of the surrounding environment, such as pH-value, ionic

593

strength and temperature (Lejars et al., 2012). As biofilms tend to develop to much 24

594

lesser thickness than, e.g., macrofouling layers composed of larvae, barnacles or

595

diatoms, they require higher shear stress which limits their application to rapidly

596

flowing systems and cannot be washed off completely, as already reported by

597

Characklis in 1990.

598

A lesser considered aspect in design of water system is access to cleaning-friendly

599

surfaces (at least with accessible control points) which can be monitored. This would

600

make it much easier for curative cleaning and to prevent biofilms to develop into

601

biofouling.

602 603

4.3.4. Surface monitoring

604

Biofouling occurs on surfaces. Therefore, surfaces are the best target for early

605

warning as well as for verification of cleaning success and anti-biofilm strategies.

606

Monitoring of biofilms and other deposits on surfaces is an attractive means for timely

607

recognition of fouling layer development, cleaning efficacy and success of anti-fouling

608

strategies.

609

From the beginning of anti-fouling research, so-called “coupons” were employed,

610

mostly in side-stream devices, in which test surfaces were exposed to conditions as

611

similar as possible to the main system, e.g., rotational reactors (van der Wende et al.,

612

1989), or the “Robbins device” implemented in the system (Ruseska et al., 1982),

613

The ideal monitoring device will provide fast and accurate information about site,

614

extent, thickness, nature (biotic/abiotic) and kinetics of fouling layer development,

615

and does so in real-time, non-destructively, on-line and cost-effective (Flemming,

616

2003). Obviously, this is a goal hard to meet.

25

617

The ideal monitoring technique allows for real-time, non-destructive, fast and

618

accurate on-line information about fouling layer buildup at a representative site, which

619

allows for distinguishing biofilms from abiotic foulants and suitable to extrapolation to

620

larger parts of the system (Flemming, 2003; Jahnknecht and Melo, 2003). An

621

interesting device has been suggested by Pereira et al. (2008), based on the

622

response of biofilms and abiotic layers to nanovibrations, developed in order to

623

monitor heat exchanger fouling as well as food and beverage industries (Pereira and

624

Melo, 2009) – this device is now applied in practice.

625

On passive metals, e.g., titanium or stainless steel, probes have been developed

626

which measure the electrochemical response to biofilm development. Commercially

627

available devices, e.g., Bi0George (Licina et al., 1999), or BIOX and ALVIM (Bruijs et

628

al., 2001; Pavanello et al., 2011; Cristiani and Perboni, 2014). The probes are

629

typically installed into a piping system, heat exchanger water box, cooling tower, or

630

side stream via a threaded connection. However, the interpretation of the signal

631

requires considerable experience.

632

An optical sensor (“Optiquad”, Strathmann et al., 2013) has been developed which

633

employs the light reflectance of biofilms growing on the tip surface of optical fibers.

634

Analysis of backscattered light allows to distinguish between biomass (proteins) and

635

activity (autofluorescence of NADH, ATP), and abiotic material (backscattered light at

636

800 nm). After proof of principle, sadly, this device also falls into the category of

637

“dream devices”, although it works on-line, in-line, automatically and in real time. But

638

it is still waiting for resources to develop it into practical application.

639

An interesting approach is the canary cell (Sim et al., 2015, 2018). It was originally

640

developed as a colloidal fouling monitor, but it turned out that it is also capable of in-

641

situ, in real time and non-destructively monitoring biofilm growth employing ultrasonic 26

642

time domain reflectometry (UTDR) by periodic dosing of silica. This technique can

643

locate biofilms on the membrane surface based on the transmission and reflection of

644

an ultrasonic wave travelling through a particular medium, e.g., biofilm, and reveals

645

its specific characteristics.

646

The best progress into wider practical application so far has been achieved in

647

membrane biofouling with side-stream membrane fouling simulators (Vrouwenvelder

648

et al., 2006; Kim et al., 2018; Subramani and Hoek, 2008). In practice, it is usually the

649

first module in which biofouling begins (Bucs et al., 2018), similar to biological filters

650

where most of the biological activity and, thus, microbial growth occurs just in the first

651

sections of the filter. They can be considered as representative for the first module.

652

This helps to avoid shutting down the process due to irreversible fouling (Bucs et al.,

653

2018; Manalo and Nijishima, 2019). Kerdi et al. (2018) presented perforated spacers

654

as creative solutions to avoid membrane biofouling.

655

The importance of monitoring systems cannot be emphasized strong enough. This

656

allows for keeping biofilm development below the threshold of interference in an

657

economically feasible way. This concept should be much more considered by fouling-

658

stricken industries.

659

The main components of a holistic anti-fouling concept are shown in Fig. 5.

660 661

Figure 5: Components of an integrated anti-fouling strategy, combined with low

662

nutrient content in the raw water (Flemming, 2016, with permission).

663 664 665 27

666

5 Conclusions

667

It is possible to live with biofilms, and all non-fouling systems do so already, because

668

they are not sterile but the effects of their biofilms are still below the threshold of

669

interference. But most of them do not know how far below this threshold they are

670

operating. Therefore, it would be extremely interesting to investigate non-fouled

671

systems and determine the level of tolerable biofilms. In the end, however, “the

672

organism always wins”. This was the essence of advice I received from Kevin

673

Marshall, my late mentor from the University of New South Wales. The key in anti-

674

fouling strategies is only to extend the time until the organism wins.

675

To achieve this, solutions require a shift of paradigms away from killing towards

676

coexistence with biofilms, and away from the so much desired and published one-

677

shot solutions towards long-term concepts. It is strongly recommended to turn to

678

integrated solutions. Building blocks for assembling such solutions are already at

679

hand, as illustrated in Fig. 5. This is where further research should be dedicated – in

680

particular, for longer-term, sustainable solutions.

681

Furthermore, it would help to adopt procedures as standardized in Water Safety

682

Plans (WHO, 2010) and implement the above mentioned building blocks. The benefit

683

would be much more success in anti-fouling and much less environmental damage

684

by biocides, disinfectants and other components which we do not want to further

685

pollute our waters.

686 687

Acknowledgements

688

Many friends and colleagues all over the world helped me on my way, and I am more

689

than grateful for that – the list would have no end. But I also want to thank some 28

690

institutions, first of all, the University of Duisburg-Essen which gave me the chance to

691

establish the Biofilm Centre, with Jost Wingender as enzyclopedical backup, creative

692

and helping me to keep ground contact, and next, the IWW Centre for Water, where I

693

could implement the department of Applied Microbiology, which was run so well by

694

my oldest colleague, Gabriela Schaule. Last not least, I am truly grateful that I can

695

continue some civilized amount of work as visiting professor at the Singapore Center

696

for Life Science and Engineering (SCELSE) with Staffan Kjelleberg and Stefan

697

Wuertz.

698

This work did not receive any specific grant from funding agencies, in the public,

699

commercial, or not-for-profit sectors

700 701

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57

Table 1: Some fields affected by biofouling Field

Problem

Reference

Ion exchangers

Contamination of water, increase

Flemming, 1987

of hydraulic resistance Membrane

Increasing of transmembrane and

Vrouwenvelder et al.,

separation

friction resistance, loss of product

2016; Ridgway et al.,

technology

quantity and quality

1983; Flemming et al., 1997

Cooling systems

Quenching heat transfer efficacy,

Characklis, 1981;

clogging

Characklis and Cooksey, 1983; Melo and Flemming, 2010;

Ship hulls

Increase of drag resistance,

Schultz, 2007; Munk

breakdown of coatings, increasing

and Kane, 2009;

corrosion rate

Swain, 2017

Ship fuel systems,

Increase of water content in fuels,

Edyvean, 2010;

piping, sea chests

emulsification, formation of

Growcott et al., 2017

(water tanks)

sludges, degradation of coatings

Fuel and hydraulic

Blockage of filters and valves,

systems

emulsification of fuel, shortening of

Suflita et al., 2012

engine life time Marine sensors

Interference with optical, electrical

Whelan and Regan,

and physical sensor functions,

2007; Venkatesan et

Marine aquaculture

increase in weight

al., 2017

Occlusion of mesh, depletion of

De Nys et al., 2009;

dissolved oxygen, accumulation of

Sievers et al., 2017

ammonia Drinking water

Contamination of chlorinated and

Wingender and

systems

non-chlorinated drinking water

Flemming, 2004;

systems with hygienically relevant

Bachmann and

microorganisms, malodour,

Edyvean, 2005; Prest

discoloration, microbially

et al., 2016;

influenced corrosion

Flemming et al., 2013 a

Washing machines,

Microbial contamination of laundry, Callewaert et al.,

dish washers, shower

smell, discoloration, hygienical

2015; Neu et al.,

hoses, other

problems, malodour, discoloration,

2017; Proctor et al.,

household water

aerolization of Legionella and

2018

systems

Pseudomonas aeruginosa

Food, beverage and

Spoiling, shortening of shelf-life,

Flemming, 2011;

milk industry

hygiene, obstruction of equipment,

Chmielewski and

downtime

Frank, 2003; Gule et al., 2016; Shi & Zhu, 2009

Paper production

Agricultural industry

Interference with production

Flemming et al., 2013

process and paper quality

b

Clogging of irrigation equipment,

Olivier et al., 2014;

Oil production

Cultural heritage

hygiene

LeJeune et al., 2001

Well and reservoir fouling,

Videla and Herrera,

acidification, microbially influenced

2005; Flemming,

corrosion

2011;

Discoloration, biodeterioration,

Koestler, 1991; Ciferri

deposition of minerals on paintings et al., 2000 Air conditioning

Aerosolization of pathogens, smell

Simmons et al., 1999

Medical devices and

Contamination and growth of

Donlan, 2001; Vickery

equipment (e.g.,

fungi, Legionella, Pseudomonas

et al., 2004; Cohen et

Contact lenses,

aeruginosa, E. coli; biofilms

al., 2006: Kackar et

inhalation masks,

causing persistent infections

al., 2017; Scotland et

systems

catheters, contact

al., 2019; Hall-

lenses, implants,

Stoodley et al., 2004

endoscopes; urethral stents)

Table 2: Innovative “dream” approaches to prevent biofouling Approach

Reference

Limitation

Smooting of surfaces,

Characklis, 1990; Jullien

Abiotic fouling compromising

electropolishing

et al., 2003; Whitehead

smoothness, adhesion of

and Verran, 2009

EPS

Zips et al., 1990; Bott,

Application, geometry of

2000; Legg et al., 2015

system, mitigation within

Physical, physicochemical

Ultrasound

biofilms, distance transducer to surface, suitable materials, frequency, Superhydrophilic surfaces

Vladkova, 2009, Xie et al., Abiotic fouling, selection for 2011; Zhang et al., 2016;

hydrophilic organisms

Younas et al., 2016; Koc et al., 2019 Superhydrophobic

Genzer and Efimenko,

Abiotic fouling, selection for

surfaces

2006; Mahalakshmi et al.,

hydrophobic organisms;

2011; Hwang et al., 2018;

stability of coating

Hizal et al., 2017 Nano-roughness

Baum et al., 2001; Bers and Wahl, 2004; Carman et al., 2006; Hizal et al., 2017

Abiotic fouling

Diamond-like surfaces (a-

Moreira et al., 2016

C:H:Si:O) Lotus effect

Abiotic fouling, long-term stability, cleanability

Barthlott et al., 2010

Liquid-gaseous phase required; abiotic fouling; sensitive to surfactants

Pulsed surface

Schaule et al., 2008; Feng Optimization of pulsing,

polarization or electrical

et al., 2018; Poortinga et

abiotic fouling, corrosion,

fields

al., 2001

narrow frequency band

UV irradiation

Marconnet et al., 2011;

Access of UV: Geometry of

Salters and Piola, 2017

system, application in membranes, particles in biofilm shield cells from UV irradiation, disposal of dead cells; only effective if feedwater is exposed to UV

UV-activated TiO2

Sunada et al., 1998

surfaces

Abiotic fouling, efficacy, removal of dead cells

Low-surface-energy

Vladkova, 2009; Townsin,

Abiotic fouling, mechanical

coatings

2009; Hwang et al., 2018

and chemical. stability

Self-polishing coatings

Lewis, 2009

Accumulation of coating material in environment

Responsive surfaces

Genzer and Efimenko,

Abiotic fouling, response

(changing pH,

2006

cycles, longterm stability

hydrophobicity,

morphology) Chemical Caustic-acid treatment

Parkar et al., 2004

Proper maintaining right concentration, temperature; stress for material

Silver/nanosilver coating

Yang et al., 2009; Zhu et

Development of silver

al., 2010; Chernousova

tolerance, abiotic fouling,

and Epple, 2013;

sensitivity to redox situation,

Cavalieri et al., 2014;

price

Königs et al., 2015 Coating with amphiphilic

Blainey and Marshall,

Chemical and mechanical

copolymers

1991; Bucs et al., 2017

stability and duration of coating, long-term efficacy, abiotic fouling

Polyether-polyamide

Louie et al., 2006

Stability of coating

Rendueles et al., 2013

Anchoring on surface, abiotic

copolymer coating Antibiofilm polysaccharides Sacrificial polyelectrolyte

fouling, selectivity of action Son et al. (2018)

cotings on membranes Urea-cleaning of

Stability of coating, replenishing, costs

Sanawar et al., 2019

membranes

Application, high concentration of urea, urease activity

Biocides generated

Wood et al., 2016

Abiotic fouling, removal of

directly on surfaces Surface-bound biocides

dead biomass Hüttinger et al., 1982; Hsu Sensitive to ionic strength, and Klibanov, 2011; Jain

abiotic fouling, capacity

et al., 2016

limited because dead biomass is not removed,

Contact killing

Klibanov, 2007; Lejars et

Sensitive to changes ionic

al., 2012; Kaur, 2016

strength and species, temperature changes, nutrient levels, pH-value; selection for tolerance

Sacrificial polyelectrolyte

Son et al. (2018)

cotings on membranes Urea-cleaning of

Stability of coating, replenishing, costs

Sanawar et al., 2019

membranes

Application, concentration of urea, urease activity

Stimuli-responsive

Shivapooja et al., 2013;

Very delicate coating, very

surfaces

Sanchet et al., 2013; Cao

early experimental stage,

et al., 2013; Lee et al.,

long-term efficacy

2014 Biological Quorum sensing (QS)

Campouris et al., 2018;

Production and application of

blocking

Iqbai et al., 2018;;

suitable QS blockers,

Mukerjee et al., 2018; Oh

selection for insensitive

et al., 2018; Solano et al.,

strains, costs, long-term

Bacteriophages

2014; Brackman and

efficacy, biodegradation of

Coenye, 2015

QS-blockers, abiotic fouling

Bhattacharjee et al., 2015; Resistance, application, Lu and Collins 2007; Ma

long-term efficacy, abiotic

et al., 2018; Milho et al.,

fouling

2019 Biomimetic/bioinspired

Pu et al., 2016; Zhang et

Abiotic fouling; long-term

surfaces

al., 2016; Bixler and

mechanical and chemical

Bushan, 2012; Baum et

stability

al., 2001; Fu et al., 2018; Shivapooja et al., 2013; Yu et al., 2011 Natural antifouling

Sateesh et al., 2016;

Availability, quantity,

compounds

Banerjee et al., 2011;

application, duration of

Wood et al., 2016; Junter

effect, biodegradation; have

et al., 2016; Xu and Liu,

to be replenished; over time,

2011; Cepas et al., 2019

select for tolerant species

Antifouling

Dobretsov et al., 2013;

Competition with

microorganisms

Satheesh et al., 2016; Gül

autochthonic population,

et al., 2018; Wood et al.,

shift to tolerant organisms;

2016

long-term stability

Kristensen et al., 2008;

Application, stability of

Cordeiro and Werner,

enzymes, self-degradation,

2011; Banerjee et al.,

long term efficacy, abiotic

Surface-bound enzymes

2011; Olsen et al., 2009;

fouling; narrow specifity of

Petrova and Sauer, 2016

enzymes

Figure 1: Emergent properties of biofilms, leading to habitat formation (from Flemming et al., 2016, with permission)

Figure 2: Tolerance and resistance of biofilm organisms (Flemming et al., 2016, with permission)

Figure 3: Fungal biofouling on an irreversibly fouled membrane, employed in river water purification (coutesy of G. Schaule)

Figure 4: Development of biofilms and the “Threshold of interference” above which biofouling is reported. ∆ = Parameter for biofilm effect, e.g., hydraulic or friction resistance, thickness etc. Inset: primary adhesion. (from Flemming, 2011, with permission)

Figure 5: Components of an integrated anti-fouling strategy, combined with low nutrient content in the raw water (Flemming, 2016, with permission).

Highlights: -

Biofilms are the oldest, most widely spread, most resilient and successful form of life on Earth

-

Biofouling is the occurrence of biofilms at the wrong place and time

-

Anti-fouling measures must be based on biofilm biology

-

Killing is not cleaning

-

A holistic approach is required to successfully combat biofouling

Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: