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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
09:00

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

Published on: May 2, 2018

Evolution of the antibiotic resistance protein, FosA, is linked to a catalytically promiscuous progenitor

Daniel W Brown1, Matthew R Schaab, William R Birmingham

  • 1Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232-0146, USA.

Biochemistry
|February 7, 2009
PubMed

Insights

Fosfomycin resistance proteins in pathogens evolved from a promiscuous progenitor. Recombining genes from Mesorhizobium loti and Pseudomonas aeruginosa created proteins conferring fosfomycin resistance, linking FosA and mlr3345 evolution.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Pathogenic microorganisms utilize FosA and FosX proteins for fosfomycin resistance.
  • These proteins are evolutionarily linked to a progenitor in the Mesorhizobium loti phn operon.

Purpose of the Study:

  • To investigate the functional and genetic relationship between Mesorhizobium loti mlr3345 and Pseudomonas aeruginosa fosA genes.
  • To understand the evolutionary origins of fosfomycin resistance mechanisms.

Main Methods:

  • In vitro homologous recombination was used to combine mlr3345 and pa1129 (a fosA gene).
  • The resulting recombinant proteins were tested for fosfomycin resistance and enzymatic activity.

Main Results:

  • The M. loti mlr3345 gene product (FosX(Ml)) exhibits minimal epoxide hydrolase and glutathione transferase activity toward fosfomycin.
  • FosX(Ml) does not confer resistance to fosfomycin.
  • Recombinant proteins from the combined genes conferred robust resistance to fosfomycin.

Conclusions:

  • The FosA resistance proteins are functionally and genetically related to the M. loti mlr3345 gene.
  • This study provides insight into the evolution of antibiotic resistance through gene recombination and functional divergence.

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