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One of the keys to the pathogenicity of Mycobacterium tuberculosis (Mtb) is the organism’s ability to resist killing by macrophages. This ability is partially overcome when macrophages have been activated by interferon (IFN)-γ. Exactly how IFN-γ enhances microbial killing is not well understood, because hundreds of macrophage genes are induced. Enhanced acidification of macrophage phagosomes, where mycobacteria survive, probably plays a role. Now, investigators have used molecular techniques to analyze the importance of phagosomal acidification in the killing of Mtb.
In initial studies, the researchers confirmed that wild-type Mtb strains are highly resistant to acid at pH 4.5 in vitro. Screening of a bank of 10,100 transposon Mtb mutants re…