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

doi:10.1016/j.cell.2005.09.012

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

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

314 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 language	English (US)
Pages (from-to)	861-873
Number of pages	13
Journal	Cell
Volume	123
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2005.09.012
State	Published - Dec 2 2005

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2005.09.012

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title = "GroEL1: A dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria",

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.",

author = "Anil Ojha and Mridula Anand and Apoorva Bhatt and Laurent Kremer and Jacobs, {William R.} and Hatfull, {Graham F.}",

note = "Funding Information: We thank Molly Scanlon for excellent technical support, John Hempel for N-terminal sequence analysis, Ashraf Ilamin in the University of Pittsburgh Proteomic Core laboratories for help with mass spectrometry, Tom Harper for photographic support, and Catherine Vilcheze for kindly providing the inhA ts mutant. This work was supported from grant AI28927 to G.F.H. and AI26170 to W.R.J. L.K. is supported by a grant from the CNRS (ATIP “Microbiologie Fondamentale”). ",

year = "2005",

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doi = "10.1016/j.cell.2005.09.012",

language = "English (US)",

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AU - Ojha, Anil

AU - Anand, Mridula

AU - Bhatt, Apoorva

AU - Kremer, Laurent

AU - Jacobs, William R.

AU - Hatfull, Graham F.

N1 - Funding Information: We thank Molly Scanlon for excellent technical support, John Hempel for N-terminal sequence analysis, Ashraf Ilamin in the University of Pittsburgh Proteomic Core laboratories for help with mass spectrometry, Tom Harper for photographic support, and Catherine Vilcheze for kindly providing the inhA ts mutant. This work was supported from grant AI28927 to G.F.H. and AI26170 to W.R.J. L.K. is supported by a grant from the CNRS (ATIP “Microbiologie Fondamentale”).

PY - 2005/12/2

Y1 - 2005/12/2

N2 - 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.

AB - 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.

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

Abstract

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