Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae

Shao Li Li1, Hong Mei Sun1, Bao Li Zhu2

  • 1Department of Bacteriology, Capital Institute of Pediatrics (CIP), Beijing 100020, China.

Abstract

Insights

Macrolide resistance in Mycoplasma pneumoniae is not solely due to 23S rRNA gene mutations. This study found that macrolide efflux pumps, involving the macB gene, also contribute significantly to resistance. Further research into these efflux mechanisms is warranted.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Macrolide resistance in Mycoplasma pneumoniae is a growing concern, particularly in Asia.
  • Known resistance mechanisms primarily involve mutations in the 23S rRNA gene.
  • These known mutations do not fully account for the observed high resistance rates.

Purpose of the Study:

  • To investigate novel genetic mutations contributing to macrolide resistance in Mycoplasma pneumoniae.
  • To explore the role of efflux pumps in mediating macrolide resistance.

Main Methods:

  • Whole-genome sequencing of 10 macrolide-resistant Mycoplasma pneumoniae clinical isolates using Illumina HiSeq2000.
  • Efflux-pump inhibition assays were performed using reserpine and CCCP to assess transporter activity.
  • Minimal inhibitory concentrations (MICs) were determined in the presence and absence of efflux pump inhibitors.

Main Results:

  • Fifty-six single nucleotide polymorphisms (SNPs) were identified compared to reference strains.
  • Four non-synonymous SNPs were found in the macB gene, encoding a macrolide-specific efflux pump.
  • Efflux pump inhibitors significantly reduced macrolide MICs, indicating the involvement of efflux pumps in resistance.

Conclusions:

  • Macrolide efflux pumps, in addition to 23S rRNA mutations, play a role in Mycoplasma pneumoniae macrolide resistance.
  • The macB gene and its encoded efflux pump are implicated in this resistance mechanism.
  • Understanding these additional resistance pathways is crucial for effective treatment strategies.