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https://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. |
DOI: | 10.1111/j.1365-2958.2010.07401.x |
Published version: | http://dx.doi.org/10.1111/j.1365-2958.2010.07401.x |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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