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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

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Evolution and spread of a multidrug-resistant Proteus mirabilis clone with chromosomal AmpC-type cephalosporinases in

M M D'Andrea1, E Literacka, A Zioga

  • 1Department of Molecular Biology, Section of Microbiology, University of Siena, Siena, Italy.

Antimicrobial Agents and Chemotherapy
|March 16, 2011
PubMed

Insights

AmpC-type cephalosporinase bla(CMY) genes in Proteus mirabilis isolates from Europe likely originated from a single transfer event from Citrobacter freundii. These genes spread via ISEcp1 transposition modules, evolving within P. mirabilis clones across a wide geographic area.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • AmpC-type cephalosporinases confer resistance to beta-lactam antibiotics.
  • The bla(CMY) gene, originating from Citrobacter freundii, is a significant cause of AmpC production.
  • Proteus mirabilis is an opportunistic pathogen frequently associated with healthcare-associated infections.

Purpose of the Study:

  • To investigate the origin and dissemination of chromosomal AmpC-type cephalosporinase bla(CMY) genes in Proteus mirabilis isolates.
  • To characterize the genetic elements involved in the transfer and integration of bla(CMY) genes into the P. mirabilis chromosome.
  • To understand the evolutionary pathways of bla(CMY) genes in P. mirabilis.

Main Methods:

  • Analysis of Proteus mirabilis isolates collected from 1999-2008 in three European countries.
  • Whole-genome sequencing and comparative analysis of bla(CMY) gene-containing mobile elements (ISEcp1 transposition modules).
  • Strain typing and phylogenetic analysis to assess clonal spread and evolution.

Main Results:

  • All analyzed P. mirabilis isolates carried bla(CMY-2)-like genes of Citrobacter freundii origin.
  • Isolates from Poland harbored diverse bla(CMY) genes, while those from Italy and Greece exclusively carried bla(CMY-16).
  • Identical ISEcp1 transposition modules (Tn6093) and insertion sites within the pepQ gene were observed across isolates, suggesting a common origin.
  • Some isolates also contained a second bla(CMY) copy within a shorter ISEcp1 module (Tn6113) downstream of the ppiD gene.
  • Sequence analysis indicated that bla(CMY) genes in P. mirabilis form a distinct cluster, potentially evolving through stepwise mutations.

Conclusions:

  • The bla(CMY) genes in the studied P. mirabilis isolates likely resulted from a single ISEcp1-mediated mobilization, transfer, and integration event from C. freundii.
  • Subsequent spread and evolution of a P. mirabilis clone facilitated the dissemination of these resistance genes over a large geographic area.
  • The findings highlight the role of mobile genetic elements in the emergence and spread of antibiotic resistance in clinically relevant bacteria.

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