Identification and characterization of the genetic changes responsible for the characteristic smooth-to-rough morphotype alterations of clinically persistent Mycobacterium abscessus

Mol Microbiol. 2013 Nov;90(3):612-29. doi: 10.1111/mmi.12387. Epub 2013 Sep 17.


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. abscessus S/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Base Sequence
  • Gene Expression Profiling
  • Genes, Bacterial*
  • Genetic Variation
  • Genome, Bacterial
  • Humans
  • INDEL Mutation
  • Lipids / biosynthesis*
  • Molecular Sequence Data
  • Multigene Family
  • Mycobacterium / classification
  • Mycobacterium / genetics*
  • Mycobacterium / pathogenicity
  • Mycobacterium Infections, Nontuberculous / microbiology*
  • Peptide Synthases / genetics*
  • Polymorphism, Single Nucleotide


  • Bacterial Proteins
  • Lipids
  • Peptide Synthases
  • non-ribosomal peptide synthase

Associated data

  • GENBANK/CAHZ01000077
  • GENBANK/CU458745
  • GENBANK/CU458896
  • GENBANK/GSE37984
  • GENBANK/HE817967