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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
Statement of
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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