Dr. Thien-Fah Mah

Biography

Research Interests

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.

Select Publications

• Mah, T. F. 2021 Giving antibiotics an assist. Science 372:1153   To read the full article, click here. 
• Khatoon, Z., McTeirnan, C. D., Suuronen, E. J., Mah, T. F. and Alarcon, E. I. 2018 Bacterial biofilm formation on implantable devices and approaches to its treatment and prevention. Heliyon 4(12):e01067 
• Hall, C. W. and Mah, T. F. 2017 Molecular mechanisms of biofilm-based antibiotic resistance in pathogenic bacteria. FEMS Microbiol. Rev. 41(3): 276-301  
• Paquette, A. R, Sterling, R. P., MacKay, G. A., Bernal, F., Mah, T. F., Gruenheid, S., Nguyen, D., Boddy, C. N. 2021 RpoN-based stapled peptides with improved DNA binding suppress Pseudomonas aeruginosa virulence. Under review at J Med Chem 
• Lazurko, C., Khatoon, Z. Goel, K., Sedlakova, V., Eren Cimenci, C., Ahumada, M., Mah, T. F., Franco, W., Suuronen, E. J. and Alarcon, E. I. 2020 Multifunctional Nano and Collagen-Based Therapeutic Materials for Skin Repair. ACS Biomater Sci Eng6(2):1124-1134 
• Hall, C. W., Farkas, E., Zhang, L. and Mah, T. F. 2019 Potentiation of aminoglycoside lethality by C4-dicarboxylates requires RpoN in antibiotic tolerant P. aeruginosa. Antimicrob Agents Chemother 63(10) pii: e01313-19. 
• Taylor, P. K., Zhang, L. and Mah, T. F. 2019 Loss of the Two-Component System TctD-TctE in Pseudomonas aeruginosa Affects Biofilm Formation and Aminoglycoside Susceptibility in Response to Citric Acid. mSphere 4(2) pii: e00102-19. 
• Hall, C. W, Hinz, A., Gagnon, L. B.-P., Zhang, L., Nadeau, J. P., Copeland, S., Saha, B., and Mah T. F. 2018. Pseudomonas aeruginosa Biofilm Antibiotic Resistance Gene ndvB Expression Requires the RpoS Stationary-Phase Sigma Factor. Appl Environ Microbiol 84(7). pii: e02762-17. 
• Lloyd, M. G., Lungren, B. R., Hall, C. W., Gagnon, L. B. P., Mah, T. F., Moffat, J. F. and Nomura, C. T. 2017. Targeting the alternative sigma factor, RpoN, to combat virulence in Pseudomonas aeruginosa.  Sci Rep 7(1): 12615. 
• Taylor, P. K., Hancock, R. E. and Mah, T. F. 2017 A Novel Small RNA is Important for Biofilm Formation and Pathogenicity in Pseudomonas aeruginosa. PLoS One 12(8):e0182582. 
• Hall, C. W., Zhang, L. and Mah, T. F. 2017 PA3225 is a transcriptional repressor of antibiotic resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 61:e02114-16. 
• McLaughlin, S., Ahumada, M., Franco, W., Mah, T. F., Seymour, R. Suuronen, E. J. and Alarcon, E. I. 2016  Sprayable peptide-modified silver nanoparticles as barrier against bacterial colonization. Nanoscale 8(46): 19200-3.
• Haddad, P., Mah, T. F. and  Mussivand, T. 2016  In vitro Assessment of Electric Currents Increasing the Effectiveness of Vancomycin against Staphylococcus epidermidis Biofilms. Artif Organs 40 (8): 804-10.  
• Huus, K., Zhang, L., Aaron, S. D., Mah, T. F. and Sad, S. 2016 Clinical isolates of Pseudomonas aeruginosa from chronically infected cystic fibrosis patients fail to activate the inflammasome. J Immunol 196(7): 3097-108.
• Alarcon, E. I., Udekwu, K., Noel, C. W., Gagnon, L. B., Taylor, P. K., Vulesevic, B., Simpson, M. J., Gkotzis, S, Islam, M. M., Lee, C. J., Richter-Dahlfors, A., Mah, T. F., Suuronen, E. J., Scaiano, J. C., Griffith, M. 2015 Safety and Efficacy of Composite Collagen-Silver Nanoparticle Hydrogels as Tissue Engineering Scaffolds. Nanoscale 7 (44):18789-98.  
• Saez, S., Fasciani, C., Stamplecoski, K. G., Gagnon, L. B., Mah, T. F., Marin, M. L., Alarcon, E. I., Scaiano, J. C. 2015 Photochemical synthesis of biocompatible and antibacterial silver nanoparticles embedded within polyurethane polymers. Photochem Photobiol Sci 14 (4): 661-4. 
• 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. Nature426:306-310.