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Research | Overview

Molecular pathogenesis of Mycobacterium tuberculosis

Research in the Husson laboratory has focused on two adaptive mechanisms of Mycobacterium tuberculosis that are relevant for the pathogenesis of tuberculosis.

One major focus of the laboratory is the regulation of transcription by the alternative sigma factors of this slow-growing bacterium. We have defined the regulons of several of the alternative sigma factors of M. tuberculosis. These include SigE and SigH, which are important in the response to oxidative and cell surface stresses, and SigL, which regulates secreted proteins and surface lipid synthesis, among others. Several of these M. tuberculosis sigma factors are required for virulence in cellular and mouse models of infection. Ongoing work is focused on the biochemical function and role in pathogenesis of specific genes regulated by these sigma factors, as well as investigation of as yet uncharacterized sigma factors.

The second major research area in Dr. Husson's laobratory focuses on signal transduction pathways of M. tuberculosis. In addition to the typical bacterial two-component signal transduction systems, this bacterium has genes encoding 11 eukaryotic-like serine/ threonine protein kinases. We have defined a role for the two essential kinases PknA and PknB in regulating cell shape and cell wall synthesis. In recent work we defined a large proportion of the M. tuberculosis phosphoproteome, identifying over 500 in vivo phosphorylation sites in over 300 M. tuberculosis proteins. Current research in this area seeks to identify the in vivo targets of individual kinases, to determine the signals that activate these kinases, and to determine the function of these molecules in M. tuberculosis physiology. We also plan to screen for direct and indirect inhibitors of kinase function.

In addition to these primary areas of research, we have recently begun a project to investigate the function of mazF family toxin systems in mycobacteria, and a translational research project to identify novel M. tuberculosis antigens.