Journal
MOLECULAR MICROBIOLOGY
Volume 90, Issue 3, Pages 612-629Publisher
WILEY
DOI: 10.1111/mmi.12387
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Funding
- organization 'Vaincre la mucoviscidose'
- Institut Pasteur [PTR 383]
- Fondation de Recherche Medicale FRM [DEQ20130326471]
- French Region Ile-de-France (Domaine d'Interet Majeur Maladies Infectieuses et Emergentes) PhD program
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Mycobacterium abscessus is an emerging pathogen that is increasingly recognized as a relevant cause of human lung infection in cystic fibrosis patients. This highly antibiotic-resistant mycobacterium is an exception within the rapidly growing mycobacteria, which are mainly saprophytic and non-pathogenic organisms. M.abscessus manifests as either a smooth (S) or a rough (R) colony morphotype, which is of clinical importance as R morphotypes are associated with more severe and persistent infections. To better understand the molecular mechanisms behind the S/R alterations, we analysed S and R variants of three isogenic M.abscessusS/R pairs using an unbiased approach involving genome and transcriptome analyses, transcriptional fusions and integrating constructs. This revealed different small insertions, deletions (indels) or single nucleotide polymorphisms within the non-ribosomal peptide synthase gene cluster mps1-mps2-gap or mmpl4b in the three R variants, consistent with the transcriptional differences identified within this genomic locus that is implicated in the synthesis and transport of Glyco-Peptido-Lipids (GPL). In contrast to previous reports, the identification of clearly defined genetic lesions responsible for the loss of GPL-production or transport makes a frequent switching back-and-forth between smooth and rough morphologies in M.abscessus highly unlikely, which is important for our understanding of persistent M.abscessus infections.
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