Regulation of the 18-kDa heat shock protein in Mycobacterium ulcerans: An alpha-crystallin orthologue that promotes biofilm formation

Sacha J Pidot, Jessica L Porter, Nicholas J Tobias, Jeffrey Anderson, Deanne Catmull, Torsten Seemann, Stephen Kidd, John K Davies, Eric Charles Reynolds, Stuart G Dashper, Timothy P Stinear

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1216 - 1231
Number of pages16
JournalMolecular Microbiology
Issue number5
Publication statusPublished - 2010

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