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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 ∆pstA1∆pstA2 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, ∆pstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a ∆pstS1 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.

ORGANISM(S): Mycobacterium tuberculosis H37Rv Mycobacterium tuberculosis str. Erdman = ATCC 35801 Mycobacterium tuberculosis CDC1551

PROVIDER: GSE83812 | GEO | 2016/06/29

SECONDARY ACCESSION(S): PRJNA327079

REPOSITORIES: GEO

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Mycobacterium tuberculosis Phosphate Uptake System Component PstA2 is Not Required for Gene Regulation or Virulence

Project description: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 âpstA1âpstA2 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, âpstA2 bacteria were more resistant to acid stress in vitro. This phenotype is intrinsic to the alternative Pst transporter since a âpstS1 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. Aerobically growing logarithmic phase Wt or pstA2 mutant or pstA1A2 double mutant strains were grown in phosphate replete media and analyzed after several hours. Experiments were repeated in triplicate.

2016-06-29 | E-GEOD-83812 | biostudies-arrayexpress

The cytoplasmic phosphate level has a central regulatory role in the phosphate starvation response of Caulobacter crescentus

Project description:In bacteria, the availability of environmental inorganic phosphate is typically sensed by the conserved PhoRB two-component signaling pathway, which uses the flux through the Pst phosphate transporter as a readout of the extracellular phosphate level to control a variety of phosphate-responsive genes. While the sensing of environmental phosphate is well-established, the regulatory effects of cytoplasmic phosphate are still unclear. Here, we disentangle the physiological and transcriptional responses of Caulobacter crescentus to changes in the environmental and cytoplasmic phosphate levels. To this end, we are uncoupling phosphate uptake from the activity of the Pst system by producing an additional, heterologous phosphate transporter. This approach reveals a bi-pronged response of C.crescentus to phosphate limitation, in which the PhoRB signaling mostly facilitates the utilization of alternative phosphate sources, whereas the cytoplasmic phosphate level controls the morphological and physiological adaptation of cells to growth in conditions of global phosphate limitation. These findings open the door to a more comprehensive understanding of phosphate signaling in bacteria.

2023-10-20 | GSE244776 | GEO

Genome-wide transcriptional response of an Avian Pathogenic Escherichia coli (APEC) Pst Mutant

Project description:Many reports show an association between the Pst system, the Pho regulon related genes and bacterial virulence. Our previous results showed that a functional Pst system is required for full virulence, resistance to serum, polymyxin B and acid shock. However, the interplay between the Pst system and virulence has an unknown molecular basis. To understand global APEC virulent strain responses to Pho regulon activation, we conducted transcriptome profiling experiments comparing the APEC chi7122 strain and its isogenic Pst mutant grown in rich phosphate medium using the Affymetrix GeneChip® E. coli Genome 2.0 Array. The Affymetrix GeneChip® E. coli Genome 2.0 Array contains the genome of the E. coli MG1655 and three pathogenic E. coli strain (EDL933, Sakai and CFT073) representing 20,366 genes. While comparing genes expression between Pst mutant and the wild type chi7122 strain, 471 genes are either up- (254) or down-regulated (217) of at least 1.5-fold, with a p-value inferior or equal to 0.05 and a false discovery rate of 2.71%. Keywords: Escherichia coli, phosphate starvation response, Pho regulon, Pst system, Affymetrix, transcriptional analysis

2008-09-15 | GSE9178 | GEO

Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation to Resist Host Immunity

Project description:Mycobacterium tuberculosis persists in the lungs of mammalian hosts despite inducing an immune response dominated by the macrophage-activating cytokine interferon-gamma (IFN-gamma). We identified the M. tuberculosis phosphate uptake system component PstA1 as a factor required to resist IFN-gamma dependent immunity. A ∆pstA1 mutant was fully virulent in IFN-gamma-/- mice but was attenuated in mice lacking the IFN-gamma-inducible nitric oxide synthase (NOS2). This phenotype suggests that ∆pstA1 bacteria are hypersensitive to an IFN-gamma-dependent immune mechanism(s) other than NOS2. In other species, the Pst system participates in phosphate-responsive gene regulation by interacting with a two-component signal transduction system. We identified genes that exhibited dysregulated expression in the ∆pstA1 mutant and showed that aberrant gene expression was dependent on the two-component system response regulator RegX3. Deletion of regX3 suppressed the replication and virulence defects of ∆pstA1 bacteria in NOS2-/- mice, suggesting that the ∆pstA1 mutant is attenuated, in part, due to aberrant RegX3-dependent gene expression. Our data imply that phosphate is an important signal controlling M. tuberculosis gene expression during replication in the lung. Aerobically growing logarithmic phase Wt or pstA1/regX3/pstA1regX3 mutant strains were grown in phosphate replete media and analyzed after several hours. Experiments were repeated in triplicate (pstA1 mutant) or quadruplicate (regX3/pstA1regX3 mutant).

2013-01-01 | E-GEOD-36998 | biostudies-arrayexpress

Mycobacterium tuberculosis Requires Phosphate-Responsive Gene Regulation to Resist Host Immunity

2013-01-01 | GSE36998 | GEO

Identification of plant vacuolar transporters mediating phosphate storage

Project description:Plant vacuoles serve as the primary intracellular compartments for inorganic phosphate (Pi) storage. Passage of Pi across vacuolar membranes plays a critical role in buffering the cytoplasmic Pi level against fluctuations of external Pi and metabolic activities. Here we demonstrate that the SPX-MFS proteins, designated as Phosphate Transporter 5 family (PHT5), also named Vacuolar Phosphate Transporter (VPT), function as vacuolar Pi transporters. Based on 31P-magnetic resonance spectroscopy analysis, Arabidopsis pht5;1 loss-of-function mutants accumulate less Pi and exhibit a lower vacuolar-to-cytoplasmic Pi ratio than controls. Conversely, overexpression of PHT5 leads to massive Pi sequestration into vacuoles and altered regulation of Pi starvation-responsive genes. Furthermore, we show that heterologous expression of OsSPX-MFS1, the rice PHT5 homolog, mediates Pi influx to yeast vacuoles. Our findings uncover a group of Pi transporters in vacuolar membranes that regulate the cytoplasmic Pi homeostasis required for the fitness of plant growth. 10-day seedlings grown on Pi-sufficient medium or followed by 1-day or 3-day Pi starvation, shoot RNA and root RNA were extracted separately

2016-03-28 | E-GEOD-74856 | biostudies-arrayexpress

Delayed phosphate starvation response in cells with abundant high-affinity transporters

Project description:Wild-type cells and cells with abundant high-affinity transporters (PHO84C) were transferred from rich medium (SD) to medium containing 0.5mM phosphate

2011-09-15 | GSE32067 | GEO

Identification of plant vacuolar transporters mediating phosphate storage

2016-03-28 | GSE74856 | GEO

Study of ecs mutation

Project description:In this study we mutated the ecsAB operon in two different Staphylococcus aureus strains, Newman and LS-1, and performed a wide characterization of phenotypic effects of the mutations. A growth defect, increased autolysis and lysostaphin sensitivity, decreased levels of cell wall proteins and altered cell surface texture indicate that Ecs deficiency causes significant changes in the cell wall. The precursor form of staphylokinase was released into the wall in an Ecs-dependent manner. Pathogenicity of the ecs mutants was studied with a mouse arthritis model. Mice inoculated with ecs mutants developed markedly milder infections than when inoculated with the wild-type strains, as was illustrated by a lower mortality, less weight loss, decreased persistence of staphylococci in the kidneys and a milder arthritis. DNA microarray analysis revealed that inactivation of Ecs in S. aureus Newman caused either up-regulation or down-regulation of genes encoding various membrane transport proteins, particularly ABC transporters and phosphate-specific transport (PST) systems. Differentially expressed were also several genes encoding proteins involved in virulence, including the virulence factor regulator protein Rot, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Furthermore, the susceptibility of ecs mutant to ribosomal antibiotics as well as the chelerythrine and sanguinarine plant alkaloids was increased. WT and ecsA mutant strains were hybridized at 3 and 6 hours of growth in rich medium (4-replicates)

2011-01-01 | E-GEOD-22353 | biostudies-arrayexpress

Saccharomyces cerevisiae

Project description:Delayed phosphate starvation response in cells with abundant high-affinity transporters

| PRJNA147607 | ENA