title: aprABC: a Mycobacterium tuberculosis complex-specific locus that modulates pH-driven adaptation to the macrophage phagosome.
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.
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14583, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Abramovitch
authors.forename: Kyle H
authors.initials: KH
authors.lastname: Rohde
authors.forename: Fong-Fu
authors.initials: FF
authors.lastname: Hsu
authors.forename: David G
authors.initials: DG
authors.lastname: Russell
mesh_terms: D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D005453:Fluorescence; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000502:physiology*; D010588:Phagosomes / Q000382:microbiology*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; C061279:PhoR protein, Bacteria; C061064:PhoP protein, Bacteria