Mah, Thien-Fah - University of Ottawa - Department of Biochemistry, Microbiology and Immunology

个人简介

B.Sc. University of British Columbia M.Sc. University of Toronto Ph.D. University of Toronto

研究领域

In most natural environments, bacteria exist in surface-attached communities called biofilms. Bacterial biofilms are formed in response to environmental signals, resulting in the transition from individual, planktonic (free-swimming) cells to a multicellular population that is attached to a solid surface and encased in an exopolysaccharide matrix. Biofilms have been implicated in causing disease in a variety of settings, including in the lungs of cystic fibrosis patients and nosocomial infections associated with medical implants. These infections can be extremely difficult to treat due to an increased resistance to antimicrobial agents that develops in biofilm-grown cells. The goal of my research is to increase our understanding of the molecular mechanisms utilized by bacteria to increase their resistance to antimicrobial agents once they become part of a biofilm. To this end, I developed a high-throughput system, using 96-well microtitre dishes, to search for mutants of Pseudomonas aeruginosa that do not develop this characteristic increase in resistance. This screening system was used in a pilot screen to identify mutants that when growing in a biofilm, were more sensitive than the wild type strain to the antibiotic tobramycin. These mutants are capable of biofilm formation and grow as well as the wild type strain in liquid culture. The screen yielded a number of interesting mutants and the lab is poised to characterize these mutants in order to understand why they are defective in developing this resistance. A better understanding of the mechanisms of biofilm resistance may lead to novel strategies to treat these biofilm-based infections.

近期论文

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Ta CA, Freundorfer M, Mah TF, Otárola-Rojas M, Garcia M, Sanchez-Vindas P, Poveda L, Maschek JA, Baker BJ, Adonizio AL, Downum K, Durst T, Arnason JT. Inhibition of bacterial quorum sensing and biofilm formation by extracts of neotropical rainforest plants. Planta Med. 2014 Mar;80(4):343-50. doi: 10.1055/s-0033-1360337. Epub 2014 Jan 31. Mah TF. Establishing the minimal bactericidal concentration of an antimicrobial agent for planktonic cells (MBC-P) and biofilm cells (MBC-B). J Vis Exp. 2014 Jan 2;(83):e50854. doi: 10.3791/50854. Zhang, L., Fritsch, M., Hammond, L., Landreville, R., Slatculescu, C., Colavita, A. and Mah, T. F. 2013 Identification of Genes Involved in Pseudomonas aeruginosa Biofilm-specific Resistance to Antibiotics. PLoS ONE 8:e61625 Mah, T. F. 2012. Biofilm-specific Antibiotic Resistance. Future Microbiol. 7: 1061-1072 Mah, T. F. 2012. Regulating antibiotic tolerance within biofilm microcolonies. J. Bacteriol. 194:4791-4792 Beaudoin, T. C., Zhang, L., Hinz, A. J., Parr, C. J. and Mah, T. F. 2012. The Biofilm-specific Antibiotic Resistance Gene, ndvB, is Important for Expression of Ethanol Oxidation Genes in Pseudomonas aeruginosa Biofilms. J. Bacteriol. 194: 3128-3136 Zhang, L., Hinz, A., Nadeau, J. P. and Mah, T. F. 2011. PA0085 provides a link between Biofilm-specific Antibiotic resistance and Type VI secretion. J. Bacteriol. 193: 5510-5513 Beaudoin, T. C., Aaron, S. , Geisbrecht, T. and Mah, T. F. 2010. Characterization of clonal strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients in Ontario, Canada. Can. J. Microbiol. 56:548-557 Keays, T., Ferris, W., Vandemheen, K. L., Chan, F., Yeung, S., Mah, T.F., Ramotar, K., Saginur, R. and S. D. Aaron 2009. A Retrospective Analysis of Biofilm Antibiotic Susceptibility Testing: A Better Predictor of Clinical Response in Cystic Fibrosis Exacerbations. JCyst Fibros 8:122-127 Zhang, L. and T.F. Mah 2008. The Involvement of a Novel Efflux System in Biofilm-specific Resistance to Antibiotics. J. Bacteriol. 190:4447-4452 Jurgens, D., S. A. Sattar, and T.F. Mah 2008 Chloraminated drinking water does not generate bacterial resistance to antibiotics in Pseudomonas aeruginosa biofilms. Let. Appl. Microbiol. 46:562-567 Mah, T.F. and G. A. O'Toole 2001. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9:34-39. Mah, T. F., B. Pitts, B. Pellock, G. C. Walker, P. S. Stewart and G. A. O'Toole 2003. A Genetic Basis for Pseudomonas aeruginosa Biofilm Antibiotic Resistance. Nature 426:306-310.