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Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis

Abstract : Comparative genomics with Staphylococcus aureus suggested the existence of a regulatory system governing beta-lactamase (BlaC) production in Mycobacterium tuberculosis. The crystal structure of Rv1846c, a winged helix regulator of previously unknown function, was solved thus revealing strong similarity to the BlaI and MecI repressors of S. aureus, which both respond to beta-lactam treatment. Using chromatin immunoprecipitation and hybridization to microarrays (ChIP-on-chip), the Rv1846c regulon was shown to comprise five separate genomic loci. Two of these mediate responses and resistance to beta-lactam antibiotics (rv1845c, rv1846c-rv1847; blaC-sigC); two encode membrane proteins of unknown function (rv1456c, rv3921c) while the last codes for ATP synthase (rv1303-atpBEFHAGDC-rv1312). The ChIP-on-chip findings were confirmed independently using electrophoretic mobility shift assays, DNAse footprinting and transcript analysis leading to Rv1846c being renamed BlaI. When cells were treated with beta-lactams, BlaI was released from its operator sites causing derepression of the regulon and upregulation of ATP synthase transcription. The existence of a potential regulatory loop between cell wall integrity and ATP production was previously unknown.
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Submitted on : Thursday, February 11, 2021 - 4:59:09 PM
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Claudia Sala, Ahmed Haouz, Frederick A. Saul, Isabelle Miras, Ida Rosenkrands, et al.. Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis. Molecular Microbiology, Wiley, 2009, 71 (5), pp.1102-1116. ⟨10.1111/j.1365-2958.2008.06583.x⟩. ⟨pasteur-03139148⟩



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