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Regulation of the 18 kDa heat shock protein in Mycobacterium ulcerans : an alpha‐crystallin orthologue that promotes biofilm formation
Author(s) -
Pidot Sacha J.,
Porter Jessica L.,
Tobias Nicholas J.,
Anderson Jeffrey,
Catmull Deanne,
Seemann Torsten,
Kidd Stephen,
Davies John K.,
Reynolds Eric,
Dashper Stuart,
Stinear Timothy P.
Publication year - 2010
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07401.x
Subject(s) - biology , mycobacterium marinum , heat shock protein , transcription (linguistics) , gene , genetics , microbiology and biotechnology , mycobacterium , linguistics , philosophy , bacteria
Summary 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.