aprABC: A Mycobacterium tuberculosis complex-specific locus that modulates pH-driven adaptation to the macrophage phagosome

Robert B. Abramovitch, Kyle H. Rohde, Fong Fu Hsu, David G. Russell

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Following phagocytosis by macrophages, Mycobacterium tuberculosis (Mtb) senses the intracellular environment and remodels its gene expression for growth in the phagosome. We have identified an acid and phagosome regulated (aprABC) locus that is unique to the Mtb complex and whose gene expression is induced during growth in acidic environments in vitro and in macrophages. Using the aprA promoter, we generated a strain that exhibits high levels of inducible fluorescence in response to growth in acidic medium in vitro and in macrophages. aprABC expression is dependent on the two-component regulator phoPR, linking phoPR signalling to pH sensing. Deletion of the aprABC locus causes defects in gene expression that impact aggregation, intracellular growth, and the relative levels of storage and cell wall lipids. We propose a model where phoPR senses the acidic pH of the phagosome and induces aprABC expression to fine-tune processes unique for intracellular adaptation of Mtb complex bacteria.

Original languageEnglish
Pages (from-to)678-694
Number of pages17
JournalMolecular Microbiology
Volume80
Issue number3
DOIs
StatePublished - May 2011

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