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Transcriptional autoregulation by Mycobacterium tuberculosis PhoP involves recognition of novel direct repeat sequences in the regulatory region of the promoter
Author(s) -
Gupta Sankalp,
Sinha Akesh,
Sarkar Dibyendu
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.09.004
Subject(s) - psychological repression , response regulator , promoter , biology , transcriptional regulation , transcription (linguistics) , two component regulatory system , gene , mycobacterium tuberculosis , consensus sequence , genetics , transcription factor , microbiology and biotechnology , gene expression , peptide sequence , mutant , tuberculosis , linguistics , philosophy , pathology , medicine
The PhoP–PhoR two‐component system is essential for virulence and intracellular growth of Mycobacterium tuberculosis (MTB) in human and mouse macrophages or in mice. Here, PhoP and truncated PhoR sensor proteins were shown to participate in phosphotransfer reactions using conserved residues characteristic of two‐component signaling systems. β‐Galactosidase activity originating from phoP promoter‐ lacZ construct was inhibited in presence of PhoP, suggesting transcriptional auto‐inhibition by the response regulator. In vitro binding of PhoP is consistent with the in vivo transcriptional repression, indicating phosphorylation‐independent assembly of the transcription initiation complex at elevated concentrations of PhoP. DNaseI protection studies reveal a consensus recognition sequence within the phoP promoter that includes three 9‐bp direct repeat units. Each repeat unit adjusts to the consensus1AC T/ G T/ G T/ GP yAP uC 9. Alteration in the sequence of the newly‐identified direct repeat units relieved phoP transcriptional repression in presence of PhoP, suggesting that PhoP represses its own expression by sequence‐specific interaction(s) with the repeat units. Together, these results identify so far unknown PhoP‐regulated genetic determinants in the regulatory region of the phoP promoter that are central to understanding of how PhoP may possibly function as a global regulator in MTB.