BRIAN J. WILKINSON |
| In the early part of my career my research focused on the bacterial cell surface – its nature and roles in antibiotic action and pathogenicity. More recently, the study of bacterial stress responses to various chemical and physical agents has become a major research theme, which often overlaps with the bacterial cell surface. The bacteria that we study are the Gram-positive bacterial pathogens Staphylococcus aureus and Listeria monocytogenes. Bacterial stress response systems play critical roles in the ability of bacteria to adapt to fluctuating stressful environments, including the host environment, and challenge with antimicrobial agents - several of which affect microbial cell surface structures. We have three major projects in the laboratory which are: | ||
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| Molecular Mechanisms of Listeria monocytogenes
Psychrotolerance L. monocytogenes is a foodborne pathogen that is the cause of listeriosis, a severe and life-threatening infection. In addition to the clinical significance of the organism, contamination of food with L. monocytogenes leads to costly product recalls. A singular feature of the organism is its ability to grow at refrigeration temperatures. Growth at low temperatures has profound effects on all aspects of microbial cell structure and function, and we only understand parts of the global picture of the response of bacteria to the cold. We are studying the roles of genes showing increased expression in response to low temperature through the creation of knockout mutations. Our ultimate goal is to improve control strategies for L. monocytogenes, and we are studying the influence of membrane active compounds on the growth of the organism at low temperatures, given the importance of membrane fluidity in low temperature growth.
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| Representative publications: Bayles, D. O., and B. J. Wilkinson. 2000. Osmoprotectants and cryoprotectants for Listeria monocytogenes. Lett. Appl. Microbiol. 30: 23-27. |
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Jones, S. L., P. Drouin, B. J. Wilkinson, and R. (P.D.II) Morse. 2002. Correlation of membrane fluidity with temperature-dependent growth characteristics of parent and a cold-sensitive, branched-chain fatty acid deficient mutant of Listeria monocytogenes. Archives of Microbiology 177: 217-222. |
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| Liu, S., J.E. Graham, L. Bigelow, P.D. Morse II, and B.J. Wilkinson. 2002. Identification of Listeria monocytogenes genes expressed in response to growth at low temperature. Appl. Environ. Microbiol. 68:1697-1705. |
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Staphylococcus aureus Methicillin and Vancomycin Resistance In the pre-antibiotic era, the mortality associated with serious systemic infections with S. aureus was 80%. Antibiotic therapy has been highly successful in treating staphylococcal infections. However, methicillin-resistant S. aureus (MRSA) strains are common worldwide, and these strains are resistant to most penicillins and cephalosporins, and to many other antibiotics. In recent years strains resistant to the sole remaining antibiotic to which S. aureus remained uniformly susceptible, vancomycin, have arisen. We are studying the mechanism of methicillin and vancomycin resistance in S. aureus. The response to antibiotics can be viewed as a stress response, and we are using genome-wide transcriptional profiling to study the response of susceptible and resistant strains to cell wall-active antibiotics.
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| Representative publications: |
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Pfeltz, R. F., V. K. Singh, J. L. Singh, M. A. Batten. C. S. Baranyk, M. J. Nadakavukaren, R. K. Jayaswal, and B. J. Wilkinson. 2000. Characterization of passage-selected vancomycin-resistant Staphylococcus aureus of diverse parental backgrounds. Antimicrob. Agents Chemother. 44: 294-303. |
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Singh, V. K., R. K. Jayaswal, and B. J. Wilkinson. 2001. Cell wall-active antibiotics stress proteins of Staphylococcus aureus identified using a proteomic approach. FEMS Microbiol. Lett. 199:79-84. |
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Singh, V.K., J.L. Schmidt, R.K. Jayaswal, and B.J. Wilkinson. 2002. Impact of sigB mutation on Staphylococcus aureus oxacillin and vacnomycin resistance varies with parental background and method of assessment. Intl. J. Antimicrob. Agents. In press. |
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| Staphylococcus aureus Stress Biology Bacteria have to contend with a fluctuating physical and chemical environment. Pathogens such as S. aureus face a variety of stresses when confronted by the host environment. These include changes in temperature, pH, nutrients, and exposure to reactive oxygen metabolites to name a few. Food microbiologists have long been concerned with the high salt tolerance of staphylococci. We are currently studying genome wide regulation of gene expression in response to various stresses using DNA microarrays provided by the National Institutes of Allergy and Infectious Diseases/Pathogen Functional Genomics Resource Center at the Institute for Genomics Research.
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| Representative publications: | ||
| Wilkinson, B.J. 1997. The biology of staphylococci. In K.B. Crossley and G.L Archer (eds.). The staphylococci in human diseases, p1-38. Churchill Livingstone Inc., New York. |
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Qoronfleh, M.W., C.A. Bortner, P. Schwatzberg, and B.J. Wilkinson. 1998. Enhanced levels of Staphylococcus aureus stress proteins GroEL and DnaK homologs early in infection of human epithelial cells. Infect. Immun. 66:3024-3027. |
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Scybert, S., R. Pechous, S. Sitthisak, M.J. Nadakavukaren, B.J. Wilkinson, and R.K. Jayaswal. 2003. An NaCl-sensitive mutant of Staphylococcus aureus ATCC 12600 has a Tn917-lacZ insertion in its ars operon. Submitted for publication. |
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