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.
|Original language||English (US)|
|State||Published - Aug 2016|
Bibliographical noteFunding Information:
This work was supported by an Irvington Post-doctoral Fellowship of the Cancer Research Institute (A.D.T.), start-up funding from the University of Minnesota (A.D.T.), National Institutes of Health (NIH) training grant T32 AI052066 (R.L.L.), NIH grant R01 AI061505 (M.I.V.) and Swiss National Science Foundation grant 310030-156945 (J.D.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2016 Tischler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.