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|Title:||Regulation of the 18 kDa heat shock protein in Mycobacterium ulcerans: An alpha-crystallin orthologue that promotes biofilm formation|
|Citation:||Molecular Microbiology, 2010; 78(5):1216-1231|
|Publisher:||Blackwell Publishing Ltd|
|Sacha J. Pidot, Jessica L. Porter, Nicholas J. Tobias, Jeffrey Anderson, Deanne Catmull, Torsten Seemann, Stephen Kidd, John K. Davies, Eric Reynolds, Stuart Dashper and Timothy P. Stinear|
|Abstract:||Mycobacterium ulcerans is the causative agent of the debilitating skin disease Buruli ulcer, which is most prevalent in Western and Central Africa. M. ulcerans shares >98% DNA sequence identity with Mycobacterium marinum, however, M. marinum produces granulomatous, but not ulcerative, lesions in humans and animals. Here we report the differential expression of a small heat shock protein (Hsp18) between strains of M. ulcerans (Hsp18(+) ) and M. marinum (Hsp18(-) ) and describe the molecular basis for this difference. We show by gene deletion and GFP reporter assays in M. marinum that a divergently transcribed gene called hspR_2, immediately upstream of hsp18, encodes a MerR-like regulatory protein that represses hsp18 transcription while promoting its own expression. Naturally occurring mutations within a 70 bp segment of the 144 bp hspR_2-hsp18 intergenic region among M. ulcerans strains inhibit hspR_2 transcription and explain the Hsp18(+) phenotype. We also propose a biological role for Hsp18, as we show that this protein significantly enhances bacterial attachment or aggregation during biofilm formation. This study has uncovered a new member of the MerR family of transcriptional regulators and suggests that upregulation of hsp18 expression was an important pathoadaptive response in the evolution of M. ulcerans from a M. marinum-like ancestor.|
|Keywords:||Biofilms; Mycobacterium marinum; Mycobacterium ulcerans; Bacterial Proteins; alpha-Crystallins; Heat-Shock Proteins; Phylogeny; Gene Expression Regulation, Bacterial; Up-Regulation; Base Sequence; Molecular Sequence Data; Promoter Regions, Genetic|
|Rights:||© 2010 Blackwell Publishing Ltd.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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