Document Detail


Enzymatic hydrolysis of trehalose dimycolate releases free mycolic acids during mycobacterial growth in biofilms.
MedLine Citation:
PMID:  20375425     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mycobacterial species, like other microbes, spontaneously form multicellular drug-tolerant biofilms when grown in vitro in detergent-free liquid media. The structure of Mycobacterium tuberculosis biofilms is formed through genetically programmed pathways and is built upon a large abundance of novel extracellular free mycolic acids (FM), although the mechanism of FM synthesis remained unclear. Here we show that the FM in Mycobacterium smegmatis biofilms is produced through the enzymatic release from constitutively present mycolyl derivatives. One of the precursors for FM is newly synthesized trehalose dimycolate (TDM), which is cleaved by a novel TDM-specific serine esterase, Msmeg_1529. Disruption of Msmeg_1529 leads to undetectable hydrolytic activity, reduced levels of FM in the mutant, and retarded biofilm growth. Furthermore, enzymatic hydrolysis of TDM remains conserved in M. tuberculosis, suggesting the presence of a TDM-specific esterase in this pathogen. Overall, this study provides the first evidence for an enzymatic release of free mycolic acids from cell envelope mycolates during mycobacterial growth.
Authors:
Anil K Ojha; Xavier Trivelli; Yann Guerardel; Laurent Kremer; Graham F Hatfull
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-06-24     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17380-9     Citation Subset:  IM    
Affiliation:
Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. ano7@pitt.edu
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Biofilms
Cloning, Molecular
Cord Factors / chemistry*
Esterases / chemistry
Hydrolysis*
Lipids / chemistry
Models, Genetic
Molecular Sequence Data
Mutation
Mycobacterium / metabolism*
Mycobacterium tuberculosis / metabolism
Mycolic Acids / chemistry*
Phenotype
Sequence Homology, Amino Acid
Grant Support
ID/Acronym/Agency:
AI064494/AI/NIAID NIH HHS; AI079288/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cord Factors; 0/Lipids; 0/Mycolic Acids; EC 3.1.-/Esterases; EC 3.1.-/serine esterase
Comments/Corrections

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