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Common evolutionary origin for the unstable virulence plasmid pMUM found in geographically diverse strains of

Timothy P Stinear1, Hui Hong, Wafa Frigui

  • 1Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France. tim.stinear@med.monash.edu.au

Journal of Bacteriology
|February 18, 2005
PubMed

Insights

Mycobacterium ulcerans virulence plasmid pMUM is a defining characteristic, though deletions can lead to loss of mycolactone toxin production. These deletions readily arise in the absence of purifying selection.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • The virulence plasmid pMUM001 in Mycobacterium ulcerans encodes giant polyketide synthases (PKS) essential for mycolactone toxin synthesis.
  • M. ulcerans strains harbor pMUM001-like elements, collectively termed pMUM, which are crucial for the bacterium's pathogenicity.

Purpose of the Study:

  • To investigate the genetic stability of the pMUM plasmid in M. ulcerans.
  • To determine the impact of plasmid deletions on mycolactone production.
  • To understand the evolutionary relationship between M. ulcerans and M. marinum based on pMUM acquisition.

Main Methods:

  • PCR and Southern hybridization to analyze pMUM gene sequences across diverse M. ulcerans strains.
  • Physical mapping of plasmids to identify deletion variants.
  • Liquid chromatography-sequential mass spectrometry (LC-MS) to analyze lipid extracts and mycolactone production.

Main Results:

  • Spontaneous deletions of pMUM001, ranging from 65-kb, were identified in M. ulcerans Agy99.
  • Three out of nine diverse M. ulcerans strains exhibited major deletions in their mycolactone PKS loci.
  • Strains with PKS deletions were incapable of producing mycolactone or related compounds.
  • pMUM gene sequences showed >98% nucleotide identity across strains, mirroring chromosomal phylogeny, supporting pMUM acquisition from M. marinum.

Conclusions:

  • pMUM is a defining genetic element of Mycobacterium ulcerans.
  • Deletions in pMUM readily occur, leading to a loss of mycolactone production, especially without strong selective pressure.
  • The presence and variability of pMUM provide insights into M. ulcerans evolution and virulence.

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