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Functional Predominance of msr(D), Which Is More Effective as mef(A)-Associated Than mef(E)-Associated, Over

Ichiro Tatsuno1, Masanori Isaka1, Katsuaki Masuno1,2

  • 11 Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences , Nagoya, Japan .

Microbial Drug Resistance (Larchmont, N.Y.)
|February 7, 2018
PubMed

Insights

The msr(D) gene, not mef(A) or mef(E) genes, is the primary driver of macrolide resistance in Streptococcus pyogenes. msr(D) function, particularly the mef(A)-associated variant, significantly impacts erythromycin resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Macrolide resistance in Streptococcus pyogenes is often attributed to mef(A) and mef(E) genes.
  • Previous research indicated a significant role for the msr(D) gene, located near mef(A), in macrolide resistance.

Purpose of the Study:

  • To investigate the functional relevance of mef(A)/mef(E) genes and their associated msr(D) genes in macrolide resistance.
  • To determine the predominant gene in conferring macrolide resistance in Streptococcus pyogenes.

Main Methods:

  • Construction and analysis of knockout strains for mef(A), mef(E), and their associated msr(D) genes.
  • Introduction of mef(A), mef(E), and msr(D) genes into specific mutant strains to assess functional complementation.
  • Evaluation of erythromycin resistance levels in engineered strains.

Main Results:

  • Knockout studies confirmed the predominant role of msr(D) over mef(A)/mef(E) in macrolide resistance.
  • Introduction experiments showed that mef(A) and mef(E) alone did not confer significant erythromycin resistance.
  • Associated msr(D) genes demonstrated significant effects on resistance, with mef(A)-associated msr(D) being more potent than mef(E)-associated msr(D).

Conclusions:

  • The msr(D) gene plays a functionally predominant role in efflux-based macrolide resistance in Streptococcus pyogenes.
  • Differences in the functional activity of mef(A)- and mef(E)-associated msr(D) genes likely contribute to the observed variations in macrolide resistance levels.
Keywords:
S. pyogenesmacrolide resistancemef(A)mef(E)msr(D)

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