The Psp system ofﾠMycobacterium tuberculosisﾠintegrates envelope stress-sensing and envelope-preserving functions

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dc.citation.firstpage408
dc.citation.issueNumber3
dc.citation.journalTitleMolecular Microbiology
dc.citation.lastpage422
dc.citation.volumeNumber97
dc.contributor.authorDatta, Pratik
dc.contributor.authorRavi, Janani
dc.contributor.authorGuerrini, Valentina
dc.contributor.authorChauhan, Rinki
dc.contributor.authorNeiditch, Matthew B.
dc.contributor.authorShell, Scarlet S.
dc.contributor.authorFortune, Sarah M.
dc.contributor.authorHancioglu, Baris
dc.contributor.authorIgoshin, Oleg
dc.contributor.authorGennaro, Maria Laura
dc.date.accessioned2017-06-06T19:07:23Z
dc.date.available2017-06-06T19:07:23Z
dc.date.issued2015
dc.description.abstractThe bacterial envelope integrates essential stress-sensing and adaptive functions; thus, envelope-preserving functions are important for survival. In Gram-negative bacteria, envelope integrity during stress is maintained by the multi-gene Psp response. Mycobacterium tuberculosis was thought to lack the Psp system since it encodes only pspA and no other psp ortholog. Intriguingly, pspA maps downstream from clgR, which encodes a transcription factor regulated by the MprAB-σE envelope-stress-signaling system. clgR inactivation lowered ATP concentration during stress and protonophore treatment-induced clgR-pspA expression, suggesting that these genes express Psp-like functions. We identified a four-gene set – clgR, pspA (rv2744c), rv2743c, rv2742c – that is regulated by clgR and in turn regulates ClgR activity. Regulatory and protein–protein interactions within the set and a requirement of the four genes for functions associated with envelope integrity and surface-stress tolerance indicate that a Psp-like system has evolved in mycobacteria. Among Actinobacteria, the four-gene module occurred only in tuberculous mycobacteria and was required for intramacrophage growth, suggesting links between its function and mycobacterial virulence. Additionally, the four-gene module was required for MprAB-σE stress-signaling activity. The positive feedback between envelope-stress-sensing and envelope-preserving functions allows sustained responses to multiple, envelope-perturbing signals during chronic infection, making the system uniquely suited to tuberculosis pathogenesis.
dc.identifier.citationDatta, Pratik, Ravi, Janani, Guerrini, Valentina, et al.. "The Psp system ofﾠMycobacterium tuberculosisﾠintegrates envelope stress-sensing and envelope-preserving functions." <i>Molecular Microbiology,</i> 97, no. 3 (2015) Wiley: 408-422. https://doi.org/10.1111/mmi.13037.
dc.identifier.doihttps://doi.org/10.1111/mmi.13037
dc.identifier.urihttps://hdl.handle.net/1911/94818
dc.language.isoeng
dc.publisherWiley
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley.
dc.titleThe Psp system ofﾠMycobacterium tuberculosisﾠintegrates envelope stress-sensing and envelope-preserving functions
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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