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Novel Mycobacterium tuberculosis anti‐σ factor antagonists control σ F activity by distinct mechanisms
Author(s) -
Beaucher Jocelyn,
Rodrigue Sébastien,
Jacques PierreÉtienne,
Smith Issar,
Brzezinski Ryszard,
Gaudreau Luc
Publication year - 2002
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 - 10.1046/j.1365-2958.2002.03135.x
Subject(s) - sigma factor , biology , mycobacterium tuberculosis , virulence factor , phosphorylation , virulence , sigma , suppressor , microbiology and biotechnology , tuberculosis , genetics , gene , promoter , gene expression , medicine , physics , pathology , quantum mechanics
Summary The aetiological agent of tuberculosis, Mycobacterium tuberculosis , encodes 13 σ factors, as well as several putative anti‐, and anti‐anti‐ σ factors. Here we show that a σ factor that has been previously shown to be involved in virulence and persistence processes, σ F , can be specifically inhibited by the anti‐σ factor UsfX. Importantly, the inhibitory activity of UsfX, in turn, can be negatively regulated by two novel anti‐anti‐σ factors. The first anti‐anti‐σ factor seems to be regulated by redox potential, and the second may be regulated by phosphorylation as it is rendered non‐functional by the introduction of a mutation that is believed to mimic phosphorylation of the anti‐anti‐σ factor. These results suggest that σ F activity might be post‐translationally modulated by at least two distinct pathways in response to different possible physiological cues, the outcome being consistent with the bacteria's ability to adapt to diverse host environments during disease progression, latency and reactivation.