The Mycobacterium tuberculosis Extracytoplasmic-Function Sigma Factor SigL Regulates Polyketide Synthases and Secreted or Membrane Proteins and Is Required for Virulence

• DOI: 10.1128/jb.187.20.7062-7071.2005
• Publication Date: 2005-09-30T16:23:42Z
• Authors: Mi-Young Hahn; Sahadevan Raman; Mauricio Anaya; Robert N. Husson
• Keywords: Sigma factor; Regulon; Transcription

Mycobacterium tuberculosis sigL encodes an extracytoplasmic function (ECF) sigma factor and is adjacent to a gene for membrane protein (Rv0736) that contains conserved HXXXCXXC sequence. This motif found in anti-sigma factors regulate several ECF factors, including those control oxidative stress responses. In this work, SigL Rv0736 were be cotranscribed, the intracellular domain of was shown interact specifically with SigL, suggesting may encode SigL. An M. mutant not more susceptible than parental strain nitrosative stresses, expression increased response these stresses. vivo, expressed from weak SigL-independent promoter also second SigL-dependent promoter. To identify SigL-regulated genes, overexpressed microarray analysis global transcription performed. Four small operons, (Rv0735)-Rv0736, mpt53 (Rv2878c)-Rv2877c, pks10 (Rv1660)-pks7 (Rv1661), Rv1139c-Rv1138c, among most highly upregulated genes sigL-overexpressing strain. start sites operons mapped, consensus sequences TGAACC -35 region CGTgtc -10 identified. vitro, purified initiated promoters sigL, mpt53, pks10. Additional four PE_PGRS appear regulated indirectly by vivo murine infection model, showed marked attenuation, indicating regulon important pathogenesis.