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

Extracytoplasmic function sigma factor σD confers resistance to environmental stress by enhancing mycolate synthesis and modifying peptidoglycan structures in Corynebacterium glutamicum
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胞质外功能 σ 因子 σD 通过增强谷氨酸棒杆菌中霉菌酸合成和修饰肽聚糖结构来赋予对环境应激的抵抗力

DOI:
10.1111/mmi.13883
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发表时间:
2017
影响因子:
3.6
通讯作者:
Inui Masayuki
Inui Masayuki
中科院分区:
生物学2区
文献类型:
--
作者:
Toyoda Koichi;Inui Masayuki

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分枝菌酸盐是在放线菌门棒状杆菌亚目的细菌中特异性合成的α-支链、β-羟基化的长链脂肪酸。它们形成一个外膜,作为一个渗透屏障,赋予致病分枝杆菌对抗生素的耐药性。虽然真菌酸生物合成途径已被深入研究,但对参与该途径的基因的转录调控的了解有限。在此,我们报道了胞质外功能σ因子σ D是谷氨酸棒杆菌亚目中霉菌酸合成基因的关键调节因子。染色质免疫沉淀结合微阵列分析检测到基因组中的σD结合区域,建立了σ D识别的共有启动子序列。σDregulon包含酰基辅酶A羧化酶亚基、酰基AMP连接酶、聚酮合酶和分枝菌酰转移酶;它们参与分枝菌酸合成。实际上,编码σ D的sigD的缺失或过表达改变了可提取的分枝菌酸盐量。在sigD的下游,rsdA编码抗σ D,并受σD依赖性启动子的控制。另一个σDregulon成员l,d-转肽酶赋予溶菌酶抗性。因此,σ D修饰肽聚糖交联并增强霉菌酸合成以提供对环境应力的抗性。
Mycolates are α‐branched, β‐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 σDis a key regulator of the mycolate synthetic genes inCorynebacterium glutamicumin the suborder. Chromatin immunoprecipitation with microarray analysis detected σD‐binding regions in the genome, establishing a consensus promoter sequence for σDrecognition. The σDregulon comprised acyl‐CoA carboxylase subunits, acyl‐AMP ligase, polyketide synthase and mycolyltransferases; they were involved in mycolate synthesis. Indeed, deletion or overexpression ofsigDencoding σDmodified the extractable mycolate amount. Immediately downstream ofsigD,rsdAencoded anti‐σDand was under the control of a σD‐dependent promoter. Another σDregulon member,l,d‐transpeptidase, conferred lysozyme resistance. Thus, σDmodifies peptidoglycan cross‐linking and enhances mycolate synthesis to provide resistance to environmental stress.
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