Division Head - Peter Phillips, MD
PubMed Publication ListYossef Av-Gay, PhD
 | Professor Associate Member Associate Member phone: 604-875-4329 yossi(at)mail.ubc.ca |
Molecular Genetics of Mycobacteria
Tuberculosis (TB) is the leading killer of adults by infectious diseases, and poses a serious challenge to international public health. So great is the concern regarding the magnitude of the modern TB epidemic that in April 1993 the World Health Organization (WHO) declared TB to be a "global emergency"; the first declaration of its kind in WHO history. Until recently, TB was considered to be a minor and decreasing problem in industrialized countries, even though M.tuberculosis is still the leading bacterial cause of human mortality in the world. More than 10 million new cases of TB arise annually, causing more than 3 million deaths each year. The steady decline of TB in industrialized countries has also recently undergone a dramatic reversal. Multidrug resistant strains of M.tuberculosis are spreading from patients to the general population. The explosive re-emergence of TB together with recent development of recombinant DNA technology in mycobacteria, has brought mycobacterial research, neglected over the past 20 years, to the forefront of microbiological research.
Dr. Av-Gay's Laboratory research is focused on the molecular pathogenesis of Mycobacterium tuberculosis in order to identify new targets for drug therapy. Using bioinformatic and pathogenomic tools, we have identified three molecular targets and we are now characterizing them for their contribution to TB pathogenesis. These targets are protein kinases of M. tuberculosis, mycothiol production and cholesterol utilization by mycobacteria.
Education
PhD - Microbial Genetics - Tel Aviv University
MSc - Microbiology - Tel Aviv University
BSc - Biology - Tel Aviv University
Recent Publications
Gopalaswamy R, Narayanan S, Chen B, Jacobs WR, Av-Gay Y. (2009). The serine/threonine protein kinase PknI controls the growth of Mycobacterium tuberculosis upon infection. FEMS Microbiol Lett. Jun;295(1):23-9.
Bach H, Wong D, Av-Gay Y. (2009). Mycobacterium tuberculosis PtkA is a novel protein tyrosine kinase whose substrate is PtpA. Biochem J. May 13;420(2):155-60.
Miller C, McMullin B, Ghaffari A, Stenzler A, Pick N, Roscoe D, Ghahary A, Road J, Av-Gay Y. (2009). Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure. Nitric Oxide. Feb;20(1):16-23.
Vilcheze, C., Av-Gay, Y. Attarian R, Liu Z, Hazbón MH, Colangeli R, Chen B, Liu W, Alland D, Sacchettini JC, Jacobs Jr WR. (2008). Mycothiol biosynthesis is essential for ethionamide susceptibility in Mycobacterium tuberculosis. Molecular Microbiology. Sep;69(5):1316-29.
Bach, H. Papavinasasundaram, K. G., Wong , D., Hmama, Z., and Av-Gay, Y. (2008) Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of Human VPS33B. Cell Host &Microbe. 3(5):316-22.
Miller,C. C. Rawat, M., Johnson, T., and Av-Gay, Y. (2007). Innate Protection of Mycobacteria Against the Antimicrobial Activity of Nitric Oxide is Provided by Mycothiol. Anti Microbial Agents and Chemotherapy, 51(9):3364-3366.
Gopalasawamy, R., Naryanan, S., Jacobs. W.R., Jr., Ko, M., and Av-Gay, Y. (2008). Protein kinase MSMEG3682 from M. smegmatis is essential for maintenance of cell wall architecture and cell division. FEMS Microbiology Letters. 278:121-127.
Mamta Rawat and and Yosef Av-Gay. (2007). Mycothiol dependent Proteins in Actinomycetes. FEMS Microbiology Reviews. 31:278-292.
Zheng, X., Papavinasasundaram, K.G., and Av-Gay, Y. (2007). Novel Substrates of Mycobacterium tuberculosis PknH serine / Threonine Kinase. BBRC. 355:162-168.
Deghmane AE, Soualhine H,Bach, H., Sendide K, Itoh S, Tam A, Noubir S, Talal A, Lo R, Toyoshima S, Av-Gay Y, Hmama Z. (2007). LpdC mediates retention of coronin-1 on M. bovis BCG vacuoles, leading to arrest in phagosome maturation. J. Cell Sci 120 (16):2796-2806
Rawat, M., Johnson, T., Cadiz, V., and Av-Gay Y. (2007). Comparative analysis of mutants in the mycothiol biosynthesis pathway in Mycobacterium smegmatis. BBRC. 363:71-76.
Bach, H., Sun, J., Wong , D., Hmama, Z. and Av-Gay Y. (2006), Mycobacterium avium ssp paratuberculosis PtpA is an endogenous tyrosine phosphatase secreted during infection. Infection and Immunity. 4:6540-6546.
Newton, G. L., Koledin, T., Ko, M., Av-Gay, Y., and Fahey, R.C. (2006). N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-D-glucopyranoside Deacetylase, a Mycothiol Biosynthetic Enzyme (MshB), is a metalloprotein subject to feedback inhibition by Mycothiol. Protein Expression and Purification. 47:542-550.
Pick, N., Rawat, M., Arad, D., Lan, J., Fan, J., Kende, A.S., and Av-Gay, Y. (2006). In Vitro Properties of Antimicrobial Bromo-Tyrosine Alkaloids. J. Med. Microbiol. 55: 407-415.
Ung S.E.K,, and Av-Gay, Y. (2006). Mycothiol Dependent Mycobacterial Response to Oxidative Stress. FEBS Letters. 580:2712-2716.
Pérez, J., Garcia, R. L., Bach, H., H de Waard, J., Jacobs, W. R. Jr., Av-Gay, Y., Bubis, J and Takiff H. (2006). Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD. BBRC. 348:6-12.
Papavinasasundaram KG., Chan B., Chung JH., Colston MJ., Davis EO., Av-Gay Y. (2005). Deletion of the Mycobacterium tuberculosis pknH Gene Confers a Higher Bacillary Load during the Chronic Phase of Infection in BALB/c Mice. J Bacteriol. 187(16):5751-60.
Dosanjh NS., Rawat M., Chung JH., Av-Gay Y. (2005). Thiol specific oxidative stress response in Mycobacteria. FEMS Microbiol PMID: 16006064.
Hestvik AL., Hmama Z., Av-Gay Y. (2005). Mycobacterial manipulation of the host cell. FEMS Microbiol PMID: 16040149.
Pick N., Cameron S., Arad D., Av-Gay Y. (2004). Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry. Biol Proced Online. 6:220-225.
Rawat M., Uppal M., Newton G., Steffek M., Fahey RC., Av-Gay Y. (2004). Targeted mutagenesis of the Mycobacterium smegmatis mca gene, encoding a mycothiol-dependent detoxification protein. J Bacteriol. 186(18):6050-8.
Cowley S., Ko M., Pick N., Chow R., Downing KJ., Gordhan BG., Betts JC., Mizrahi V., Smith DA., Stokes RW., Av-Gay Y. (2004). The Mycobacterium tuberculosis protein serine/threonine kinase PknG is linked to cellular glutamate/glutamine levels and is important for growth in vivo. Mol Microbiol. 52(6):1691-702.
Wiens T., Redelmeier T., Av-Gay Y. (2004). Development of a liposome formulation of ethambutol. Antimicrob Agents Chemother. 48(5):1887-8.
Selected Publications
Karlsgot Hestvik, A. L. Hmama, Z. and Av-Gay, Y. (2003). Kinome analysis of host response to mycobacterial infection. Infection and Immunity. 71:5514-5522.
Rawat, M., Kovacevic, S., Billman-Jacobe, H., and Av-Gay, Y. (2003). Inactivation of mshB, a key gene in mycothiol biosynthesis pathway in Mycobacterium smegmatis. Microbiology 149: 1341-1349.
Newton, G. L., Koledin, T., Rawat, M., Gorovitz, B., Fahey, R.C., and Av-Gay, Y. (2003). The Glycosyltransferase Gene Encoding the Enzyme Catalyzing the First Step of Mycothiol Biosynthesis (mshA) . J. Bacteriology. 185: 3476-3479.
PDF Rawat, M., Heys, J., and Av-Gay, Y. (2003) Identification and characterization of a diamide sensitive mutant of Mycobacterium smegmatis. FEMS Microbiol. Lett. 220:161-169.
Rawat, M., Newton, G. L., Ko, M., Martinez, J.G., R.C. Fahey and Av-Gay, Y. (2002) Mycothiol deficient mutants in Mycobacterium smegmatis are hypersensitive to alkylating agents, free radicals and antibiotics. Anti microbial agents and Chemotherapy. 46: 3348-3355.
Cowley, S. C., Babakaiff, R., and Av-Gay, Y. (2002). Expression and localization of Mycobacterium tuberculosis tyrosine protein phosphatase PtpA. Research in Microbiology. 153:233-241.
Drews, S.J., Hung, F., and Av-Gay, Y. (2001). A Protein Kinase Inhibitor As An Antimycobacterial Agent. FEMS Microbiol. Lett. 205: 369-374.
PDF Cowley S. C., and Av-Gay, Y. (2001). Monitoring promoter activity and protein localization in Mycobacterium spp. using Green fluorescent protein. Gene, 264:225-231.
Av-Gay, Y., and Sabouti, R. (2000). Cholesterol is accumulated by mycobacteria but its degradation is limited to non-pathogenic fast-growing mycobacteria. Canadian Journal of Microbiology. 46:826-831.
PDF Av-Gay, Y., and Everett. M. (2000). The eukaryotic-like serine threonine kinase of Mycobacterium tuberculosis. Review. Trends in Microbiology. 8:238-244.
Av-Gay, Y., Jamil, S., and Drews, S. (1999). Cloning Expression and Characterization of M. tuberculosis Protein Kinase B. Infection and Immunity. 67:5676-5682.
PDF Av-Gay, Y., (1999). Uncontrolled release of harmful microorganisms, letter. Science 284:1621.