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Selective killing of nonreplicating mycobacteria. | LitMetric

AI Article Synopsis

  • - Antibiotics are generally more effective against replicating bacteria, but there is a crucial need to target nonreplicating bacteria like Mycobacterium tuberculosis (Mtb) for global health.
  • - Researchers screened for inhibitors of the enzyme dihydrolipoamide acyltransferase (DlaT) in Mtb, which is essential for the bacteria's survival and virulence in the host.
  • - The screening identified specific rhodanine compounds that effectively kill nonreplicating Mtb by working alongside the host's immune responses, potentially enhancing existing treatments for infectious diseases.

Article Abstract

Antibiotics are typically more effective against replicating rather than nonreplicating bacteria. However, a major need in global health is to eradicate persistent or nonreplicating subpopulations of bacteria such as Mycobacterium tuberculosis (Mtb). Hence, identifying chemical inhibitors that selectively kill bacteria that are not replicating is of practical importance. To address this, we screened for inhibitors of dihydrolipoamide acyltransferase (DlaT), an enzyme required by Mtb to cause tuberculosis in guinea pigs and used by the bacterium to resist nitric oxide-derived reactive nitrogen intermediates, a stress encountered in the host. Chemical screening for inhibitors of Mtb DlaT identified select rhodanines as compounds that almost exclusively kill nonreplicating mycobacteria in synergy with products of host immunity, such as nitric oxide and hypoxia, and are effective on bacteria within macrophages, a cellular reservoir for latent Mtb. Compounds that kill nonreplicating pathogens in cooperation with host immunity could complement the conventional chemotherapy of infectious disease.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423947PMC
http://dx.doi.org/10.1016/j.chom.2008.02.003DOI Listing

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