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Phagotrophic protozoa: A new weapon against pathogens?
Medical Hypotheses (2008) 70, 141–142
http://intl.elsevierhealth.com/journals/mehy
Phagotrophic protozoa: A new weapon against pathogens? Ahmet Nacar
a,*
, Emel Nacar
b
a
Baskent University Medical Faculty, Department of Histology and Embryology, 06510 Eimusgut, Ankara, Turkey b Fatih University Medical Faculty, Ankara, Turkey Received 13 February 2007; accepted 17 March 2007
Summary Immune suppression is one of the most important factors contributing mortality in systemic diseases like HIV, cancer or diabetes. Moreover, in autoimmune diseases immune suppression itself becomes the only choice of therapy. Finally, fatal bacterial infections occur. As antibiotics get stronger, severity of their side effects increase and more resistant organisms develop. The war between antibiotics and pathogens becomes a never ending story while human body gets weaker day by day. Therefore we should develop new methods against bacterial infections. We have suggested that the protists controlling the bacterial growth effectively in aquatic environments could be used in the human body to cope with human pathogens. Million years of a balanced aquatic ecosystem could be a clue for us to search for better and more natural fighting methods against human infectious agents. c 2007 Elsevier Ltd. All rights reserved.
Background In the human body, first scientific reports about bacterial interference and bacteriotherapy was published in late 1800s. Besides bacterial therapy, parasitic worms have also been reported to be good for patients with certain diseases. Mingomataj et al. [1] showed that helmints could protect themselves from the allergic reaction by an alteration in the immune response thereby causing an inhibitory effect on allergic symptoms. In studies by Saunders et al. [2] and Summers et al. [3]; autoimmune type I diabetes mellitus and chronic inflammatory bowel * Corresponding author. Tel.: +90 3122341010x1570/ 5053190609; fax: +90 3122341180. E-mail address: [email protected] (A. Nacar).
diseases were treated with parasitic worms, respectively. Most of these studies have focused on helmints’ immune biasing ability. But they have another strong feature: phagocytosis.
The hypotheses Heterotrophic protozoa, both flagellates and ciliates, are the most important bacterial consumers in aquatic environments [4–6]. They balance bacterial population with the help of viruses [7] and maintain aquatic ecosystems. Bacteria-consuming ability of protozoa was introduced to human benefit in a study by Sibille et al. [8]. That study showed that Escherichia coli was lost from the protozoalocated drinking water distribution network more
0306-9877/$ - see front matter c 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2007.03.037
142
Nacar and Nacar
rapidly than nano-filtered network in which no protozoa were determined. If so, could not we benefit from these bacterivores in bacterial diseases of the human body? Such good examples of this kind of application are leech and larval therapies. It sounds irritating to place larvae or leech on the human body. But results are hopeful. Therefore, there could also be several advantages of using predators inside the human body.
Potential indications Antibiotic-resistant bacterial infections elsewhere in the body could be the target. For instance bacterial populations of pathological foci in patients with wound, traumatic, and burns infections could be treated with bacterivory protozoa. Pathologic organisms of nasocomial infections, diabetic wounds or any infection in immune-supressed individuals like those with cancer, HIV, or steroid therapy could be sensitive to predation by phagotrophic protozoa. Besides resistant infections, in fact predation therapy with bacterivores should be the first choice in certain infections to avoid the development of resistance. Perhaps the most effective aspect of bacterivore therapy would be little or no resistance to therapy. Because the chance of a digested organism to transfer something for its next generation to fight better is very lower than that of a free and living organism after an antibiotic attack. If we look at the biosphere, we will see that predators hunt and preys escape with the same tactics since the day they were formed, or improved themselves so little as compared with the organisms being more and more resistant in couple of years.
Potential risks Allergic reaction is the first risk. The reaction of immune system to helmints in human body was investigated and found that helmints could protect themselves from the host defense by altering certain immune mechanisms thereby causing a suppression in allergic symptoms [1]. This selfprotective behaviour of nematods were suggested to be an evolutionary response. In other words, this immune biasing effect could provide protozoa enough time to consume pathogenic organisms.
Secondly, infections carried by protozoa could occur. To avoid the risk of secondary infection, colonization in pathogen-free animals, culturing in sterile culture mediums in the presence of antibiotics, and rigorous tests to confirm the absence of viral or bacterial pathogens should be performed. Finally, to avoid an uncontrolled invasion by protists, the immune system could later be supported with anti-protist drugs. Furthermore, a genetic modification causing self-destruction of protozoa in a timely manner could be performed.
Conclusion This era brings several negative factors like stress, cancer, HIV or side-effected treatments weakening our defense against infections. Immune suppression and resistant organisms make infections more dangerous. In this picture we need to improve alternative approaches to fight infections. Phagotrophic protozoa could help us in this war both by consuming certain existing pathogens and preventing resistance.
References [1] Mingomataj EC, Xhixha F, Gjata E. Helminths can protect themselves against rejection inhibiting hostile respiratory allergy symptoms. Allergy 2006;61:400–6. [2] Saunders KA, Raine T, Cooke A, Lawrence CE. Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun 2007;75:397–407. [3] Summers RW, Elliott DE, Qadir K, Urban Jr JF, Thompson R, Weinstock JV. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 2003;98:2034–41. [4] Gonzalez JM. Bacterivory rate estimates and fraction of active bacterivores in natural protist assemblages from aquatic systems. Appl Environ Microbiol 1999;65:1463–9. [5] Sherr BF, Sherr EB, Rassoulzadegan F. Rates of digestion of bacteria by marine phagotrophic protozoa: temperature dependence. Appl Environ Microbiol 1988;54:1091–5. [6] Sime-Ngando T, Demers S, Juniper SK. Protozoan bacterivory in the ice and the water column of a cold temperate lagoon. Microbial Ecol 1999;37:95–106. [7] Bettarel Y, Amblard C, Sime-Ngando T, Carrias JF, Sargos D, Garabetian F, et al. Viral lysis, flagellate grazing potential, and bacterial production in Lake Pavin. Microbial Ecol 2003;45:119–27. [8] Sibille I, Sime-Ngando T, Mathieu L, Block JC. Protozoan bacterivory and Escherichia coli survival in drinking water distribution systems. Appl Environ Microbiol 1998;64: 197–202.
Available online at www.sciencedirect.com
http://intl.elsevierhealth.com/journals/mehy
Phagotrophic protozoa: A new weapon against pathogens? Ahmet Nacar
a,*
, Emel Nacar
b
a
Baskent University Medical Faculty, Department of Histology and Embryology, 06510 Eimusgut, Ankara, Turkey b Fatih University Medical Faculty, Ankara, Turkey Received 13 February 2007; accepted 17 March 2007
Summary Immune suppression is one of the most important factors contributing mortality in systemic diseases like HIV, cancer or diabetes. Moreover, in autoimmune diseases immune suppression itself becomes the only choice of therapy. Finally, fatal bacterial infections occur. As antibiotics get stronger, severity of their side effects increase and more resistant organisms develop. The war between antibiotics and pathogens becomes a never ending story while human body gets weaker day by day. Therefore we should develop new methods against bacterial infections. We have suggested that the protists controlling the bacterial growth effectively in aquatic environments could be used in the human body to cope with human pathogens. Million years of a balanced aquatic ecosystem could be a clue for us to search for better and more natural fighting methods against human infectious agents. c 2007 Elsevier Ltd. All rights reserved.
Background In the human body, first scientific reports about bacterial interference and bacteriotherapy was published in late 1800s. Besides bacterial therapy, parasitic worms have also been reported to be good for patients with certain diseases. Mingomataj et al. [1] showed that helmints could protect themselves from the allergic reaction by an alteration in the immune response thereby causing an inhibitory effect on allergic symptoms. In studies by Saunders et al. [2] and Summers et al. [3]; autoimmune type I diabetes mellitus and chronic inflammatory bowel * Corresponding author. Tel.: +90 3122341010x1570/ 5053190609; fax: +90 3122341180. E-mail address: [email protected] (A. Nacar).
diseases were treated with parasitic worms, respectively. Most of these studies have focused on helmints’ immune biasing ability. But they have another strong feature: phagocytosis.
The hypotheses Heterotrophic protozoa, both flagellates and ciliates, are the most important bacterial consumers in aquatic environments [4–6]. They balance bacterial population with the help of viruses [7] and maintain aquatic ecosystems. Bacteria-consuming ability of protozoa was introduced to human benefit in a study by Sibille et al. [8]. That study showed that Escherichia coli was lost from the protozoalocated drinking water distribution network more
0306-9877/$ - see front matter c 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2007.03.037
142
Nacar and Nacar
rapidly than nano-filtered network in which no protozoa were determined. If so, could not we benefit from these bacterivores in bacterial diseases of the human body? Such good examples of this kind of application are leech and larval therapies. It sounds irritating to place larvae or leech on the human body. But results are hopeful. Therefore, there could also be several advantages of using predators inside the human body.
Potential indications Antibiotic-resistant bacterial infections elsewhere in the body could be the target. For instance bacterial populations of pathological foci in patients with wound, traumatic, and burns infections could be treated with bacterivory protozoa. Pathologic organisms of nasocomial infections, diabetic wounds or any infection in immune-supressed individuals like those with cancer, HIV, or steroid therapy could be sensitive to predation by phagotrophic protozoa. Besides resistant infections, in fact predation therapy with bacterivores should be the first choice in certain infections to avoid the development of resistance. Perhaps the most effective aspect of bacterivore therapy would be little or no resistance to therapy. Because the chance of a digested organism to transfer something for its next generation to fight better is very lower than that of a free and living organism after an antibiotic attack. If we look at the biosphere, we will see that predators hunt and preys escape with the same tactics since the day they were formed, or improved themselves so little as compared with the organisms being more and more resistant in couple of years.
Potential risks Allergic reaction is the first risk. The reaction of immune system to helmints in human body was investigated and found that helmints could protect themselves from the host defense by altering certain immune mechanisms thereby causing a suppression in allergic symptoms [1]. This selfprotective behaviour of nematods were suggested to be an evolutionary response. In other words, this immune biasing effect could provide protozoa enough time to consume pathogenic organisms.
Secondly, infections carried by protozoa could occur. To avoid the risk of secondary infection, colonization in pathogen-free animals, culturing in sterile culture mediums in the presence of antibiotics, and rigorous tests to confirm the absence of viral or bacterial pathogens should be performed. Finally, to avoid an uncontrolled invasion by protists, the immune system could later be supported with anti-protist drugs. Furthermore, a genetic modification causing self-destruction of protozoa in a timely manner could be performed.
Conclusion This era brings several negative factors like stress, cancer, HIV or side-effected treatments weakening our defense against infections. Immune suppression and resistant organisms make infections more dangerous. In this picture we need to improve alternative approaches to fight infections. Phagotrophic protozoa could help us in this war both by consuming certain existing pathogens and preventing resistance.
References [1] Mingomataj EC, Xhixha F, Gjata E. Helminths can protect themselves against rejection inhibiting hostile respiratory allergy symptoms. Allergy 2006;61:400–6. [2] Saunders KA, Raine T, Cooke A, Lawrence CE. Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun 2007;75:397–407. [3] Summers RW, Elliott DE, Qadir K, Urban Jr JF, Thompson R, Weinstock JV. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 2003;98:2034–41. [4] Gonzalez JM. Bacterivory rate estimates and fraction of active bacterivores in natural protist assemblages from aquatic systems. Appl Environ Microbiol 1999;65:1463–9. [5] Sherr BF, Sherr EB, Rassoulzadegan F. Rates of digestion of bacteria by marine phagotrophic protozoa: temperature dependence. Appl Environ Microbiol 1988;54:1091–5. [6] Sime-Ngando T, Demers S, Juniper SK. Protozoan bacterivory in the ice and the water column of a cold temperate lagoon. Microbial Ecol 1999;37:95–106. [7] Bettarel Y, Amblard C, Sime-Ngando T, Carrias JF, Sargos D, Garabetian F, et al. Viral lysis, flagellate grazing potential, and bacterial production in Lake Pavin. Microbial Ecol 2003;45:119–27. [8] Sibille I, Sime-Ngando T, Mathieu L, Block JC. Protozoan bacterivory and Escherichia coli survival in drinking water distribution systems. Appl Environ Microbiol 1998;64: 197–202.
Available online at www.sciencedirect.com