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Resistance phenotypes conferred by macrolide phosphotransferases

Olivier Chesneau1, Krassimira Tsvetkova, Patrice Courvalin

  • 1Unité des Agents Antibactériens, Institut Pasteur, Paris, France.

FEMS Microbiology Letters
|February 17, 2007
PubMed

Insights

This study investigated how different mph genes confer erythromycin resistance through phosphorylation in bacteria. Certain mph genes provide resistance to macrolides, ketolides, and other antibiotics like azithromycin and telithromycin.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Erythromycin resistance is a growing concern in bacterial infections.
  • Enzymatic modification, specifically phosphorylation, is a key mechanism of macrolide resistance.
  • The mph genes encode erythromycin-phosphorylating enzymes, but their specific resistance profiles are not fully characterized.

Purpose of the Study:

  • To compare the resistance phenotypes conferred by various mph genes encoding erythromycin-phosphorylating enzymes.
  • To investigate the role of specific mph genes in resistance to different macrolide and ketolide antibiotics.

Main Methods:

  • Cloning of mph genes into a macrolide-susceptible Escherichia coli strain (AG100A) with a disrupted AcrAB pump.
  • Phenotypic analysis of antibiotic resistance profiles conferred by individual mph genes.
  • Sequence analysis of a novel mph gene variant.

Main Results:

  • A novel 882 bp mph gene sequence conferred erythromycin resistance via phosphorylation.
  • mph(C) and mph(B) conferred resistance to spiramycin, while mph(A) uniquely conferred azithromycin resistance.
  • All four investigated mph genes conferred resistance to telithromycin.

Conclusions:

  • Different mph genes exhibit distinct substrate specificities, contributing to varied macrolide and ketolide resistance patterns.
  • The characterization of mph gene-mediated resistance is crucial for understanding and combating antibiotic resistance.
  • The widespread presence of mph genes in Enterobacteriaceae highlights their public health significance.

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