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The P sp system of M ycobacterium tuberculosis integrates envelope stress‐sensing and envelope‐preserving functions
Author(s) -
Datta Pratik,
Ravi Janani,
Guerrini Valentina,
Chauhan Rinki,
Neiditch Matthew B.,
Shell Scarlet S.,
Fortune Sarah M.,
Hancioglu Baris,
Igoshin Oleg A.,
Gennaro Maria Laura
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13037
Subject(s) - biology , cell envelope , mycobacterium tuberculosis , gene , microbiology and biotechnology , virulence , envelope (radar) , genetics , tuberculosis , escherichia coli , medicine , radar , pathology , computer science , telecommunications
Summary The bacterial envelope integrates essential stress‐sensing and adaptive functions; thus, envelope‐preserving functions are important for survival. In G ram‐negative bacteria, envelope integrity during stress is maintained by the multi‐gene P sp response. M ycobacterium tuberculosis was thought to lack the P sp 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 ‐σ E envelope‐stress‐signaling system. clgR inactivation lowered ATP concentration during stress and protonophore treatment‐induced clgR ‐ pspA expression, suggesting that these genes express P sp‐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 P sp‐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 ‐σ E 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.