Whole Cell Screen for Inhibitors of pH Homeostasis in Mycobacterium tuberculosis Academic Article uri icon

Overview

MeSH Major

  • Acid-Base Equilibrium
  • Antitubercular Agents
  • Homeostasis
  • Mycobacterium tuberculosis

abstract

  • Bacterial pathogens like Mycobacterium tuberculosis (Mtb) encounter acidic microenvironments in the host and must maintain their acid-base homeostasis to survive. A genetic screen identified two Mtb strains that cannot control intrabacterial pH (pHIB) in an acidic environment; infection with either strain led to severe attenuation in mice. To search for additional proteins that Mtb requires to survive at low pH, we introduced a whole-cell screen for compounds that disrupt pHIB, along with counter-screens that identify ionophores and membrane perturbors. Application of these methods to a natural product library identified four compounds of interest, one of which may inhibit novel pathway(s). This approach yields compounds that may lead to the identification of pathways that allow Mtb to survive in acidic environments, a setting in which Mtb is resistant to most of the drugs currently used to treat tuberculosis.

publication date

  • July 30, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3728290

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0068942

PubMed ID

  • 23935911

Additional Document Info

start page

  • e68942

volume

  • 8

number

  • 7