Extracytoplasmic function sigma factor sigma(D) confers resistance to environmental stress by enhancing mycolate synthesis and modifying peptidoglycan structures in Corynebacterium glutamicum

Mycolates are -branched, -hydroxylated, long-chain fatty acid specifically synthesized in bacteria in the suborder Corynebacterineae of the phylum Actinobacteria. They form an outer membrane, which functions as a permeability barrier and confers pathogenic mycobacteria to resistance to antibiotics. Although the mycolate biosynthetic pathway has been intensively studied, knowledge of transcriptional regulation of genes involved in this pathway is limited. Here, we report that the extracytoplasmic function sigma factor sigma(D) is a key regulator of the mycolate synthetic genes in Corynebacterium glutamicum in the suborder. Chromatin immunoprecipitation with microarray analysis detected sigma(D)-binding regions in the genome, establishing a consensus promoter sequence for sigma(D) recognition. The sigma(D) regulon comprised acyl-CoA carboxylase subunits, acyl-AMP ligase, polyketide synthase and mycolyltransferases; they were involved in mycolate synthesis. Indeed, deletion or overexpression of sigD encoding sigma(D) modified the extractable mycolate amount. Immediately downstream of sigD, rsdA encoded anti-sigma(D) and was under the control of a sigma(D)-dependent promoter. Another sigma(D) regulon member, l,d-transpeptidase, conferred lysozyme resistance. Thus, sigma(D) modifies peptidoglycan cross-linking and enhances mycolate synthesis to provide resistance to environmental stress.