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Macrolides mediate transcriptional activation of the msr(E)-mph(E) operon through histone-like nucleoid-structuring

Yitao Duan1,2, Shuangqing Liu3, Yuting Gao1

  • 1College of Environmental Science and Engineering, Nankai University, Tianjin, China.

The Journal of Antimicrobial Chemotherapy
|November 8, 2021
PubMed
Abstract

Insights

Macrolides activate the msr(E)-mph(E) operon, conferring high antibiotic resistance. This regulation involves specific promoter regions and proteins like HNS and CRP in bacteria such as Klebsiella pneumoniae.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • The msr(E)-mph(E) operon is widespread in bacteria, providing high-level macrolide resistance.
  • Understanding macrolide regulation of this operon is crucial for combating antibiotic resistance.

Purpose of the Study:

  • To investigate whether macrolides regulate the transcription of the msr(E)-mph(E) operon.
  • To elucidate the mechanism of macrolide-induced transcription.

Main Methods:

  • Whole Genome Sequencing (WGS) of Klebsiella pneumoniae isolates.
  • Quantitative PCR to assess operon transcription.
  • Reporter plasmid construction, gene knockout, and complementation experiments.
  • Sequence analysis to determine operon prevalence.

Main Results:

  • Macrolide treatment up-regulated the msr(E)-mph(E) operon in K. pneumoniae isolates.
  • Identified J10/J35 regions as critical for macrolide-induced promoter activation.
  • Histone-like nucleoid-structuring protein (HNS) and cAMP receptor protein (CRP) were involved in the activation.
  • The operon was found in diverse bacteria, notably Acinetobacter baumannii and K. pneumoniae, primarily from human clinical samples.

Conclusions:

  • Macrolides activate msr(E)-mph(E) operon transcription via HNS and CRP in K. pneumoniae and E. coli.
  • This regulatory mechanism is likely conserved across diverse bacterial species.

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