LspA-independent action of globomycin on Mycobacterium tuberculosis.
OBJECTIVE
The objective of this study was to investigate the antimicrobial activity and specificity of globomycin, an inhibitor of lipoprotein signal peptidase II (LspA), against Mycobacterium tuberculosis.


METHODS
The mycobactericidal and mycobacteriostatic activity of globomycin was determined by optical density and cfu plating. The specificity of globomycin was determined by western immunoblotting using anti-MPT83 antibody.


RESULTS
Globomycin is mycobactericidal at concentrations>or=40 mg/L. However, at 80 mg/L, the processing of the lipoprotein MPT-83 is unaffected and growth-inhibitory effect of globomycin is unchanged in an lspA null mutant (DeltalspA::lspAmut) lacking the putative drug target.


CONCLUSIONS
Globomycin kills M. tuberculosis through a mechanism that is independent of LspA.
Banaiee
Niaz
N
Department of Medicine (Division of Infectious Diseases), NYU School of Medicine, New York, NY 10016, USA. nbanaiee@stanford.edu
Jacobs
William R
WR
Ernst
Joel D
JD
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010455:Peptides; D011480:Protease Inhibitors; C017339:globomycin; D016282:Aspartic Acid Endopeptidases; C095652:signal peptidase II