Associate Member of the Staff
Department of Molecular Genetics
email:
University of Vermont, B.S., 1982, Clinical Microbiology
Michigan State University, Ph.D., 1999, Microbiology
Dartmouth Medical School, Postdoc, 2002, NIH, Training Fellowship in Molecular Pathogenesis
It is now widely recognized that most bacteria found in natural or industrial settings persist in complex microbial communities attached to surfaces or associated with interfaces (biofilms), not as free floating organisms, and not alone. In fact, biofilms represent biological systems with a high level of organization where bacteria form structured coordinated functional communities; and it is within these systems that most bacterial activity occurs in nature. Although this fundamental aspect of microbiology has long been recognized, we are only just beginning to understand how these communities develop and how they function. Fortunately, recent advances in microscopy, techniques for growing biofilms and molecular methods for monitoring the location, growth and activities of bacteria have provided the necessary tools to study this under-appreciated area of biology.
One of the primary reasons for the dramatic increase in biofilm research is the link to chronic infections. Clinicians have discovered that bacterial biofilms form not only on teeth, but on both dead and living tissue, as well as on a variety of medical implants, including in-dwelling catheters, as well as surgical implants (such as heart valves, artificial joints and dental implants). The formation of biofilms on these surfaces presents two major problems. First, in the biofilm mode of growth, bacteria are protected from attack by immune cells and are recalcitrant to antibiotic therapy, therefore, once these bacterial communities form they are extremely difficult to eliminate with conventional anti-microbial therapies. Furthermore, biofilms represent a source of bacteria that can be shed into the body, thus leading to chronic systemic infections. The only recourse is to remove the contaminated tissue or implant, which is costly and results in additional trauma to the patient. The Centers for Disease Control estimates that bacteria growing as biofilms cause 65% of the infections treated by physicians in the developed world, and the majority of these infections are associated with the use of in-dwelling medical devices, resulting in an estimated 200,000 systemic infections and 20,000–40,000 deaths each year at costs exceeding $1 billion.
Periodontal disease is a chronic biofilmbased disease that occurs in more than 35% of the adult population in the U.S. The combined activities of anaerobic bacteria in the subgingival plaque are strongly implicated in the progression of adult periodontitis. Porphyromonas gingivalis is an anaerobe that resides within the biofilm community in the subgingival crevice of the oral cavity, and is regarded as a major causative agent in the initiation and progression of severe manifestations of periodontal disease, a condition characterized by destruction of the tissue supporting the gums, and ultimately, tooth loss. It is evident that the ability of bacteria to persist and grow within subgingival plaque is central to this disease state, yet little is known about the physiology of periodontal pathogens when growing as a biofilm.
The focus of our research is the study of the relationship between biofilm development and the pathogenicity of P. gingivalis. The switch from a benign, surface attached state to a disease-causing state is central to the virulence of this opportunistic pathogen. It is clear that changes in expression of surface structures play an important role in this switch. Capsule production by P. gingivalis is linked to a virulent phenotype that disseminates causing systemic infections. Our research has shown that capsule production also blocks biofilm formation. Hence, regulation of capsule expression plays a central role in both pathogenesis and biofilm formation. The overall goal of current studies is to increase our understanding of the signals and regulatory networks that coordinate expression of surface structures (e.g., capsule, fimbriae, surface associated proteases, and adhesin proteins) that affect the transition from a surface attached state to a free-living state.
Davey ME. (2008) Tracking dynamic interactions during plaque formation. J. Bacteriol.190(24):7869-7870.
Davey ME, Costerton JW. (2006) Molecular genetics analyses of biofilm formation in oral pathogens. Periodontol. 2000 42(1):13-26.
Davey ME. (2006) Techniques for the growth of Porphyromonas gingivalis biofilms. Periodontol. 2000 42(1):27-35.
Davey ME, Duncan MJ. (2006) Enhanced biofilm formation and loss of capsule synthesis: Deletion of a putative glycosyltransferase in Porphyromonas gingivalis. J. Bacteriol. 188 (15):5510-5523.
Davey ME, Caiazza NC, O'Toole GA. (2003) Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J. Bacteriol. 185(3):1027-1036.
Christine Alberti-Segui, Ph.D.
