Center for Biofilm Engineering

Science Article Overview

Bacterial Biofilms: A Common Cause of Persistent Infections

by J.W. Costerton, P.S. Stewart, and E.P. Greenberg, Science, 21 May 1999, 284(5418):1318-1322.

CBE researchers Dr. Bill Costerton and Dr. Phil Stewart, along with microbiologist Dr. Peter Greenberg of the University of Iowa, are co-authors of an invited review on biofilm infections that appeared in the May 21, 1999 issue of Science. The cover of Science features an image from Dr. Greenberg’s lab showing aggregated bacteria establishing a biofilm on lung tissue cells. Highlighted in the article is the power of interdisciplinary research that combines life scientists with engineers and mathematicians. This interdisciplinary approach is underscored by the fact that one of the co-authors (Stewart) is a chemical engineer. National Science Foundation and industry co-sponsored Engineering Research Centers like the CBE have led the way in developing new paradigms of interdisciplinary research and education. The article chronicles the growing recognition of the importance of biofilm formation in many persistent medical infections. It also points toward possible innovative strategies for controlling such infections based on recent advances in the understanding of the genetics and molecular biology of biofilm development.

Examples of biofilm-related infections are the deterioration of gums and jawbone that can eventually lead to loss of teeth (periodontal disease); middle ear infection familiar to millions of children and their parents (otitis media); and a fatal lung infection (cystic fibrosis pneumonia). A significant number of people are affected by biofilm infections which develop on medical devices implanted in the body such as catheters (tubes used to conduct fluids in or out of the body), artificial joints, and mechanical heart valves. When implanted material becomes colonized by microorganisms, a slow developing but persistent infection results. The infection can be nearly impossible to eradicate. Usually the implant must be removed, a procedure that is often costly, dangerous, and traumatic for the patient.

A hallmark of all biofilm diseases is the chronic nature of the infections. A biofilm infection may linger for months, years, or even a lifetime. It may not ever kill its victim, though the infection can compromise quality of life. Biofilm infections can smolder indefinitely even in people with healthy immune systems. Microorganisms in a biofilm manage to evade killing by the diverse arsenal of antimicrobial agents unleashed by the immune system as well as by antibiotics. Research at the CBE has begun to shed light on the mechanisms of biofilm resistance to antimicrobial agents. These mechanisms include failure of the antimicrobial agent to fully penetrate the biofilm, the presence of niches within the biofilm where bacteria exist in a dormant and protected state, and the possibility that microorganisms adopt a distinct and intrinsically resistant phenotype. This helps us understand how infections can persist even after a round of antibiotic therapy and why they are so difficult to resolve.

Research reviewed in the article suggests that we are justified in viewing biofilm formation as a genetically programmed developmental process. Microorganisms that attach to a surface turn on new genes, turn off others, and embark on a developmental path that is completely different from that taken by microbes growing in traditional suspended cultures. One of the remarkable discoveries to which CBE researchers contributed, is that bacteria in biofilm exchange intercellular signals, analogous to hormones, that are important in mediating the formation of the complex architecture of natural biofilms. The recognition that biofilm formation is a biologically regulated process is an insight that carries profound medical significance because it envisions a multitude of new chemotherapeutic targets. New agents will be developed to control biofilm infections by interfering with the biofilm developmental process thereby allowing the immune response or conventional antibiotic therapy to subdue the infection.

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