Mycolactone gene expression is controlled by strong SigA-like promoters with utility in studies of Mycobacterium ulcerans and buruli ulcer

NJ Tobias; T Seemann; SJ Pidot; JL Porter; L Marsollier; E Marion; F Letournel; T Zakir; J Azuolas; JR Wallace; H Hong; JK Davies; BP Howden; PDR Johnson; GA Jenkin; TP Stinear

Journal article

Mycolactone gene expression is controlled by strong SigA-like promoters with utility in studies of Mycobacterium ulcerans and buruli ulcer

NJ Tobias, T Seemann, SJ Pidot, JL Porter, L Marsollier, E Marion, F Letournel, T Zakir, J Azuolas, JR Wallace, H Hong, JK Davies, BP Howden, PDR Johnson, GA Jenkin, TP Stinear

Plos Neglected Tropical Diseases | Published : 2009

DOI: 10.1371/journal.pntd.0000553

Download PDF

Abstract

Mycolactone A/B is a lipophilic macrocyclic polyketide that is the primary virulence factor produced by Mycobacterium ulcerans, a human pathogen and the causative agent of Buruli ulcer. In M. ulcerans strain Agy99 the mycolactone polyketide synthase (PKS) locus spans a 120 kb region of a 174 kb megaplasmid. Here we have identified promoter regions of this PKS locus using GFP reporter assays, in silico analysis, primer extension, and site-directed mutagenesis. Transcription of the large PKS genes mlsA1 (51 kb), mlsA2 (7 kb) and mlsB (42 kb) is driven by a novel and powerful SigA-like promoter sequence situated 533 bp upstream of both the mlsA1 and mlsB initiation codons, which is also functio..

View full abstract

University of Melbourne Researchers

Torsten Seemann Author

Sacha Pidot Author

Jessica Porter Author

Ben Howden Author

Grants

Funding Acknowledgements

This research was supported in part by the National Health and Medical Research Council of Australia. This research was also supported by the Fondation Francaise Raoul Follereau, the Institut National de la Sante et de la Recherche Medicale ( INSERM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.