Mycobacterium tuberculosis-secreted phosphatases: from pathogenesis to targets for TB drug development.
Mycobacterium tuberculosis (Mtb) infects human alveolar macrophages and relies on the inhibition of phagosome acidification and maturation. This is, in part, dependent on the disruption of host signaling networks within the macrophage. In recent years, Mtb-secreted protein- and lipid-phosphatases protein-tyrosine phosphatase A (PtpA), PtpB, and secreted acid phosphatase M (SapM) have been shown to contribute to Mtb pathogenicity. Here, we review the current knowledge on PtpA, PtpB, and SapM focusing on their ability to interfere with host functions. We further explore how these phosphatase-dependent host-pathogen interactions can be targeted for novel tuberculosis (TB) drug discovery and examine the ongoing development of inhibitors against these phosphatases.
Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6H 3Z6, Canada.
Dennis
D
Wong
Joseph D
JD
Chao
Yossef
Y
Av-Gay
D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054884:Host-Pathogen Interactions; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000472:pathogenicity; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014376:Tuberculosis / Q000188:drug therapy / Q000209:etiology*
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010744:Phosphoric Monoester Hydrolases