title: Regulation of the 18 kDa heat shock protein in Mycobacterium ulcerans: an alpha-crystallin orthologue that promotes biofilm formation.
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.
authors.affiliation: Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Sacha J
authors.initials: SJ
authors.lastname: Pidot
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Porter
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Tobias
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Anderson
authors.forename: Deanne
authors.initials: D
authors.lastname: Catmull
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.forename: Stephen
authors.initials: S
authors.lastname: Kidd
authors.forename: John K
authors.initials: JK
authors.lastname: Davies
authors.forename: Eric
authors.initials: E
authors.lastname: Reynolds
authors.forename: Stuart
authors.initials: S
authors.lastname: Dashper
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D018441:Biofilms; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019910:Mycobacterium marinum / Q000145:classification / Q000235:genetics / Q000378:metabolism; D019911:Mycobacterium ulcerans / Q000145:classification / Q000235:genetics / Q000502:physiology*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D015854:Up-Regulation; D038201:alpha-Crystallins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D038201:alpha-Crystallins