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Biofilm: The challenge that presents opportunities
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It may not come as a surprise to learn that treatment of biofilm-related infections consume a massive part of the health care resources worldwide. In the United States, up to 500,000 primary blood stream infections occur annually among 150 million intravascular devices implanted. It is estimated that in 2014, more than $1 billion will be spent to treat periprosthetic joint infection of the hip and the knee.
Biofilm refers to a complex community of microorganisms that form on a substrate surface, such as heart valves, contact lenses, intravascular devices, teeth, pace makers and indwelling catheters. Biofilm also can at times form on the surface of affected living tissues. The initial step in the formation of a biofilm is for microorganisms to attach to the surface of a foreign material and proliferate to form a protected community of microorganisms. The umbrella of the extracellular matrix produced by the organisms affords protection against the immune surveillance of the host and is largely impenetrable to antibiotics. The organisms in the biofilm communicate through sophisticated molecular mechanisms, such as quorum sensing, that allows them to refine the microenvironment appropriately for consumption of limited nutrition and provides them with the best “insight” to determine the optimal time to detach from the community and metastasize to other locations.
Javad Parvizi
The formation of biofilm is also the reason we find it difficult to diagnose or detect infection associated with orthopedic devices or eradicate them when such a structure is formed on the surface of these devices. The available diagnostic modalities currently rely on the isolation of planktonic (free-floating) organisms and formation of biofilm affords the organisms the ability to evade detection.
A few months before his passing, Bill Costerton, known to most as the god of biofilm, declared that the one of the most exciting areas in medicine for the years to come would be biofilm science. His vision was right on target. Recent years has witnessed a flurry of scientific activities that have unraveled some of the most exciting discoveries. A few areas of biofilm science are worth outlining.
Through high throughput screening, scientists have discovered small molecules that play a critical role in formation of biofilm and devised approaches for biofilm disruption. In a recent publication in the Proceedings of National Academy of Sciences, Sun and colleagues described their experience of screening 55,000 chemical compounds to search for inhibitors of gene expression of a key Streptococcus pyogenes virulence factor, streptokinase. A lead compound was identified that appeared to prevent the expression of many key virulence factors by S. pyogenes and also Staphylococcus aureus. Administration of this compound to mice protected them against infection by these two organisms. Scientists are also exploring the role of enzymes in disrupting the extracellular matrix around biofilms that will make the organisms vulnerable. One such enzyme, dispersin B, is produced by Actinobacillus actinomycetemcomitans that can disrupt biofilm produced by other bacteria. The coating of device surfaces by bacteriostatic or bactericidal surfaces in another approach in our fight against biofilm. Coating with vancomycin, silver and interestingly, furanones produced by red alga Delisea pulchra, are some of the coatings that have been tested. Another interesting approach for prevention of biofilm formation explores the utility of anti-adhesion surfaces that prevent attachment of bacterial to a foreign surface, the critical first step in formation of a biofilm. A group of well-recognized and respected biofilm scientists from Missouri have applied trimethylsilane (TMS) plasma nanocoatings using low-temperature plasma technology to coat surfaces of stainless steel and titanium that prevents bacterial adhesion and biofilm formation by Staphylococcus epidermidis.
The tireless efforts of scientists who have lent their intellectual talents to the field are likely to result in novel approaches for treatment of infection that goes beyond the traditional antibiotics with all their innate limitations. The future is bright.
References:
Ma Y. Antimicrob. Agents Chemother. 2012;doi:10.1128/AAC.01739-12.
Sun H. Proc. Natl. Acad. Sci. 2012;doi: 10.1073/pnas.1201031109.
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Disclosures: Parvizi is a consultant to Zimmer, Smith & Nephew, 3M and Convatec.