Michael Glickman, MD

Microbial Pathogenesis of Mycobacterium Tuberculosis

Enlarge Image Mycobacterium tuberculosis Virulent M. tuberculosis stained with Auramine Rhodamine. These bacteria exhibit “cording” a morphologic marker of virulence where bacteria form serpentiine ropes or “cords.” We have used this morphology to identify genes required for synthesis of cell wall based pathogenesis determinants.

Tuberculosis remains a major cause of mortality worldwide, and new antimicrobials that would shorten TB chemotherapy are badly needed.

Our laboratory studies the pathogenesis of infection with Mycobacterium tuberculosis (Mtb) through a multidisciplinary approach that includes microbial genetics, biochemistry, molecular biology, lipid biochemistry, and immunology.

Our general approach to understanding strategies of mycobacterial pathogenesis is the creation and analysis of defined bacterial mutants. The long-term goal of these studies is to identify and understand bacterial molecules essential for Mtb pathogenesis that would be attractive therapeutic targets and to gain insight into the novel physiology of myocbacteria.

The laboratory is actively investigating three major areas:

1. M. tuberculosis cell envelope lipids as direct pathogenesis effector molecules which modify host innate immune recognition
2. Regulation of M. tuberculosis cell envelope composition and virulence by Regulated Intramembrane Proteolysis (RIP)
3. Mycobacterial Nonhomologous end-joining (NHEJ) mediated by ATP dependent DNA ligases