title: Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 Is Not Required for Gene Regulation or Virulence.
abstract: The Mycobacterium tuberculosis genome encodes two complete high-affinity Pst phosphate-specific transporters. We previously demonstrated that a membrane-spanning component of one Pst system, PstA1, was essential both for M. tuberculosis virulence and for regulation of gene expression in response to external phosphate availability. To determine if the alternative Pst system is similarly required for virulence or gene regulation, we constructed a deletion of pstA2. Transcriptome analysis revealed that PstA2 is not required for regulation of gene expression in phosphate-replete growth conditions. PstA2 was also dispensable for replication and virulence of M. tuberculosis in a mouse aerosol infection model. However, a ΔpstA1ΔpstA2 double mutant was attenuated in mice lacking the cytokine interferon-gamma, suggesting that M. tuberculosis requires high-affinity phosphate transport to survive phosphate limitation encountered in the host. Surprisingly, ΔpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ΔpstS1 mutant exhibited similar acid resistance. Our data indicate that the two M. tuberculosis Pst transporters have distinct physiological functions, with the PstA1 transporter being specifically involved in phosphate sensing and gene regulation while the PstA2 transporter influences survival in acidic conditions.
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.|School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Anna D
authors.identifier: http://orcid.org/0000-0001-8404-0250
authors.initials: AD
authors.lastname: Tischler
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Leistikow
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Pavithra
authors.initials: P
authors.lastname: Ramakrishnan
authors.affiliation: Department of Immunology and Microbiology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Martin I
authors.initials: MI
authors.lastname: Voskuil
authors.affiliation: School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: John D
authors.initials: JD
authors.lastname: McKinney
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000220:Adaptation, Biological; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D005798:Genes, Bacterial; D006863:Hydrogen-Ion Concentration; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D010710:Phosphates / Q000378:metabolism*; D017384:Sequence Deletion; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D014774:Virulence / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D010710:Phosphates; C102499:PstA-2 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma