GroEL1: A dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria
GroEL1: A dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria
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DOI：
10.1016/j.cell.2005.09.012
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发表时间：
2005-12-02
期刊：
影响因子：
64.5
通讯作者：
Hatfull, GF
中科院分区：
文献类型：
--
作者：
Ojha, A;Anand, M;Hatfull, GF
分枝杆菌在编码两种GroEL旁系同源物GroEL 1和GroEL 2方面是不寻常的。GroEL 2是必不可少的，大概提供管家伴侣功能，而groEL 1是非必需的，包含的attB网站噬菌体Bxb 1整合，并编码一个推定的伴侣与不寻常的结构特征。通过噬菌体Bxb 1整合使耻垢分枝杆菌groEL 1基因失活允许正常的增殖生长，但阻止成熟生物膜的形成。GroEL 1在生物膜形成期间特异性地调节分枝菌酸盐（分枝杆菌细胞壁的长链脂肪酸组分）的合成，并与KasA（参与分枝菌酸合成的II型脂肪酸合酶的关键组分）物理缔合。生物膜的形成与短链（C-56-C-68）脂肪酸的合成增加有关，霉菌酸谱改变的菌株（包括抗结核药物异烟肼的InhA突变体和过度表达KasA的菌株）在生物膜形成方面有缺陷。
Mycobacteria are unusual in encoding two GroEL paralogs, GroEL1 and GroEL2. GroEL2 is essential-presumably providing the housekeeping chaperone functions-while groEL1 is nonessential, contains the attB site for phage Bxb1 integration, and encodes a putative chaperone with unusual structural features. Inactivation of the Mycobacterium smegmatis groEL1 gene by phage Bxb1 integration allows normal planktonic growth but prevents the formation of mature biofilms. GroEL1 modulates synthesis of mycolates-long-chain fatty acid components of the mycobacterial cell wall-specifically during biofilm formation and physically associates with KasA, a key component of the type II Fatty Acid Synthase involved in mycolic acid synthesis. Biofilm formation is associated with elevated synthesis of short-chain (C-56-C-68) fatty acids, and strains with altered mycolate profiles-including an InhA mutant resistant to the antituberculosis drug isoniazid and a strain overexpressing KasA-are defective in biofilm formation.