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Understanding biofilms—are we getting closer?
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Understanding biofilms—are we getting closer? For more on HipA see Science 2009; 323: 396–401; DOI:10.1126/science.1163806
Science Source/Science Photo Library
For more on biofilm formation see Proc Natl Acad Sci USA 2009; 106: 280–85; DOI:10.1073/ pnas.0810940106
Recent research has uncovered the structure of a protein known to cause persistence in Escherichia coli biofilms. This protein, HipA, is already known to be associated with cell dormancy and bacterial persistence, and enables bacteria to resist drug treatment—becoming dormant and then switching back to active growth, unaffected by any treatment during dormancy. “This study has important implications, moving the field into understanding how to prevent both regrowth of biofilms and the mechanisms of antibiotic resistance”, Tom Ford (University of New England, Biddeford, ME, USA) told TLID. “Understanding the biochemistry of the emergence of antimicrobialresistant phenotypes should give us insight into how we might effectively treat an infection to prevent the growth of biofilms and persistent infection”, continues Ford. From endocarditis to gastric ulcers, the medical problems caused by biofilms can be endless. Biofilms can form on contact with any surface, be it stagnant water, medical equipment, or even oil. A biofilm is an intricate and complex structure of bacterial colonies surrounded by an extracellular polymeric matrix. A biofilm can contain several different species of bacteria, the complex structure can contain specific channels in which nutrients can circulate, and cells in different areas of the biofilm can undergo phenotypic shifts, which can switch the behaviour of the different regions of the biofilm
Colour-enhanced SEM of a Staphylococcus sp biofilm
216
structure; all of these factors may explain why biofilms are able persist in the most hostile of environments, and do not usually respond to conventional antibiotic therapy. Persistent biofilm infections have been associated with surgical and medical devices—such as intravenous catheters, prosthetic heart valves, cardiac pacemakers, and hip replacements. Bacterial endocarditis has been associated with bacteria that have entered the bloodstream from the skin or oral cavity; these then go onto colonise implanted heart valves or endothelial surfaces of the heart causing chronic health problems. Staphylococci have been commonly linked with the contamination of medical equipment. However, the variation in biofilm structures and their behaviour can make it very difficult to pinpoint when a chronic infection may be caused by a biofilm, if at all. The pathogenesis of biofilms in infectious diseases is still a controversial topic among researchers. According to Daniel Rhoads (Southwest Regional Wound Care Center, Lubbock, TX, USA), “the developing world is still struggling with acute infections like cholera and malaria. The developed world has largely overcome these diseases, and is now facing a foe that it does not know how to conquer: chronic bacterial infections associated with biofilms”. Scientists at the Centers for Disease Control and Prevention (Atlanta, GA, USA) estimate that 65% of infections in the developed world are the result of drug-resistant biofilms, highlighting the importance of ongoing research into combating biofilm infections. Ford thinks that the field of biofilminduced infection is something “that has emerged as medicine becomes more effective. In the past antibiotics did a reasonable job of controlling persistent infections, but now biofilms are increasingly becoming the focus of attention”. “It is important to eliminate the biofilm infection, instead of just trying to suppress it. Unfortunately,
there are few, if any, drugs that can do this. Currently the best means of attacking biofilms is with antibiotics in typically high doses, for a long duration, and using multiple agents”, says Rhoads. Biofilms have caused substantial complications of surgical procedures—for example, infected orthopaedic implants have resulted in the added expense of having to remove and replace the implants, or in severe cases, amputation. In the past decade, scientists have provided some answers as to how, and why, biofilms may be drug resistant. First, previous research has shown that there may be problems with the drug being physically unable to enter the biofilm, either by not being able to penetrate the biofilm or by being bound up in the extracellular matrix of the biofilm. Second, enhanced biofilm formation in some species of bacteria may be associated with environmental stress. In a recent study by Lopez and colleagues, for example, there are hints at an understanding of the mechanism of biofilm formation by Bacillus subtillis. “We are particularly excited because we have found a very unusual signal transduction mechanism”, says Roberto Kolter (Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA). “I believe this points at new ways of discovering novel compounds that might block this signal mechanism and have substantial therapeutic value”, explains Kolter. The recent increase in research into biofilms is encouraging, says Kolter, but we still have a lot to learn. “Biofilms can be wildly diverse and form in countless ways, so different strategies need to be devised”, says Kolter. “It is becoming more and more clear that there will not be universal targets common to all biofilms”. “There may be some that are common to several pathogens, but clearly not something that can be used to eradicate all biofilms” he concludes.
Nayanah Siva www.thelancet.com/infection Vol 9 April 2009
Understanding biofilms—are we getting closer? For more on HipA see Science 2009; 323: 396–401; DOI:10.1126/science.1163806
Science Source/Science Photo Library
For more on biofilm formation see Proc Natl Acad Sci USA 2009; 106: 280–85; DOI:10.1073/ pnas.0810940106
Recent research has uncovered the structure of a protein known to cause persistence in Escherichia coli biofilms. This protein, HipA, is already known to be associated with cell dormancy and bacterial persistence, and enables bacteria to resist drug treatment—becoming dormant and then switching back to active growth, unaffected by any treatment during dormancy. “This study has important implications, moving the field into understanding how to prevent both regrowth of biofilms and the mechanisms of antibiotic resistance”, Tom Ford (University of New England, Biddeford, ME, USA) told TLID. “Understanding the biochemistry of the emergence of antimicrobialresistant phenotypes should give us insight into how we might effectively treat an infection to prevent the growth of biofilms and persistent infection”, continues Ford. From endocarditis to gastric ulcers, the medical problems caused by biofilms can be endless. Biofilms can form on contact with any surface, be it stagnant water, medical equipment, or even oil. A biofilm is an intricate and complex structure of bacterial colonies surrounded by an extracellular polymeric matrix. A biofilm can contain several different species of bacteria, the complex structure can contain specific channels in which nutrients can circulate, and cells in different areas of the biofilm can undergo phenotypic shifts, which can switch the behaviour of the different regions of the biofilm
Colour-enhanced SEM of a Staphylococcus sp biofilm
216
structure; all of these factors may explain why biofilms are able persist in the most hostile of environments, and do not usually respond to conventional antibiotic therapy. Persistent biofilm infections have been associated with surgical and medical devices—such as intravenous catheters, prosthetic heart valves, cardiac pacemakers, and hip replacements. Bacterial endocarditis has been associated with bacteria that have entered the bloodstream from the skin or oral cavity; these then go onto colonise implanted heart valves or endothelial surfaces of the heart causing chronic health problems. Staphylococci have been commonly linked with the contamination of medical equipment. However, the variation in biofilm structures and their behaviour can make it very difficult to pinpoint when a chronic infection may be caused by a biofilm, if at all. The pathogenesis of biofilms in infectious diseases is still a controversial topic among researchers. According to Daniel Rhoads (Southwest Regional Wound Care Center, Lubbock, TX, USA), “the developing world is still struggling with acute infections like cholera and malaria. The developed world has largely overcome these diseases, and is now facing a foe that it does not know how to conquer: chronic bacterial infections associated with biofilms”. Scientists at the Centers for Disease Control and Prevention (Atlanta, GA, USA) estimate that 65% of infections in the developed world are the result of drug-resistant biofilms, highlighting the importance of ongoing research into combating biofilm infections. Ford thinks that the field of biofilminduced infection is something “that has emerged as medicine becomes more effective. In the past antibiotics did a reasonable job of controlling persistent infections, but now biofilms are increasingly becoming the focus of attention”. “It is important to eliminate the biofilm infection, instead of just trying to suppress it. Unfortunately,
there are few, if any, drugs that can do this. Currently the best means of attacking biofilms is with antibiotics in typically high doses, for a long duration, and using multiple agents”, says Rhoads. Biofilms have caused substantial complications of surgical procedures—for example, infected orthopaedic implants have resulted in the added expense of having to remove and replace the implants, or in severe cases, amputation. In the past decade, scientists have provided some answers as to how, and why, biofilms may be drug resistant. First, previous research has shown that there may be problems with the drug being physically unable to enter the biofilm, either by not being able to penetrate the biofilm or by being bound up in the extracellular matrix of the biofilm. Second, enhanced biofilm formation in some species of bacteria may be associated with environmental stress. In a recent study by Lopez and colleagues, for example, there are hints at an understanding of the mechanism of biofilm formation by Bacillus subtillis. “We are particularly excited because we have found a very unusual signal transduction mechanism”, says Roberto Kolter (Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA). “I believe this points at new ways of discovering novel compounds that might block this signal mechanism and have substantial therapeutic value”, explains Kolter. The recent increase in research into biofilms is encouraging, says Kolter, but we still have a lot to learn. “Biofilms can be wildly diverse and form in countless ways, so different strategies need to be devised”, says Kolter. “It is becoming more and more clear that there will not be universal targets common to all biofilms”. “There may be some that are common to several pathogens, but clearly not something that can be used to eradicate all biofilms” he concludes.
Nayanah Siva www.thelancet.com/infection Vol 9 April 2009