Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/63730
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Type: Journal article
Title: Regulation of the 18 kDa heat shock protein in Mycobacterium ulcerans: An alpha-crystallin orthologue that promotes biofilm formation
Author: Pidot, S.
Porter, J.
Tobias, N.
Anderson, J.
Catmull, D.
Seemann, T.
Kidd, S.
Davies, J.
Reynolds, E.
Dashper, S.
Stinear, T.
Citation: Molecular Microbiology, 2010; 78(5):1216-1231
Publisher: Blackwell Publishing Ltd
Issue Date: 2010
ISSN: 0950-382X
1365-2958
Statement of
Responsibility: 
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.
RMID: 0020102913
DOI: 10.1111/j.1365-2958.2010.07401.x
Appears in Collections:Molecular and Biomedical Science publications

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