Nonclassical transpeptidases of Mycobacterium tuberculosis alter cell size, morphology, the cytosolic matrix, protein localization, virulence, and resistance to β-lactams.
Virtually all bacteria possess a peptidoglycan layer that is essential for their growth and survival. The β-lactams, the most widely used class of antibiotics in human history, inhibit D,D-transpeptidases, which catalyze the final step in peptidoglycan biosynthesis. The existence of a second class of transpeptidases, the L,D-transpeptidases, was recently reported. Mycobacterium tuberculosis, an infectious pathogen that causes tuberculosis (TB), is known to possess as many as five proteins with L,D-transpeptidase activity. Here, for the first time, we demonstrate that loss of L,D-transpeptidases 1 and 2 of M. tuberculosis (LdtMt1 and LdtMt2) alters cell surface morphology, shape, size, organization of the intracellular matrix, sorting of some low-molecular-weight proteins that are targeted to the membrane or secreted, cellular physiology, growth, virulence, and resistance of M. tuberculosis to amoxicillin-clavulanate and vancomycin.
Taskforce To Study Resistance Emergence & Antibiotic Discovery Technology, Johns Hopkins University, Baltimore, Maryland, USA.
Maia K
MK
Schoonmaker
William R
WR
Bishai
Gyanu
G
Lamichhane
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity*; D010458:Peptidyl Transferases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D014376:Tuberculosis / Q000382:microbiology*; D014774:Virulence; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047090:beta-Lactams; D010458:Peptidyl Transferases