GroEL1: A dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria

Anil Ojha, Mridula Anand, Apoorva Bhatt, Laurent Kremer, William R. Jacobs, Graham F. Hatfull

Research output: Contribution to journalArticle

237 Scopus citations

Abstract

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 (C56-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.

Original languageEnglish (US)
Pages (from-to)861-873
Number of pages13
JournalCell
Volume123
Issue number5
DOIs
StatePublished - Dec 2 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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