Molecular Genetics of Beta-Lactam Sensitivity and Resistance in Mycobacterium tuberculosis

Mycobacterium tuberculosis threatens global health. Its thick, impermeable cell wall renders it tolerant to high doses of many antibiotics. While we understand the biochemical functions of many cell wall-modifying enzymes, we often do not understand their physiological functions: their spatiotemporal roles in the cell cycle, their substrate preferences, or their individual effects on the macromolecular architecture of the cell wall complex. Mycobacterium tuberculosis possesses five peptidoglycan transpeptidases, five lytic transglycosylases, and numerous other peptidoglycan-modifying enzymes that lack precisely-understood roles.