RamAp Is an Efflux Pump Regulator Carried by an IncHI2 Plasmid

Yu-Ping Hong1,2, You-Wun Wang2, Bo-Han Chen2

  • 1Ph.D. Program in Medical Biotechnology, National Chung Hsing Universitygrid.260542.7, Taichung, Taiwan.

Insights

A novel plasmid-borne gene, ramAp, was discovered in Salmonella Goldcoast, activating efflux pumps and increasing antimicrobial resistance. This finding raises concerns about the global spread of antibiotic resistance in bacterial pathogens.

Area of Science:

  • Microbiology
  • Genetics
  • Epidemiology

Background:

  • Salmonella enterica serovar Goldcoast strains exhibit varying resistance to azithromycin and quinolones.
  • Multidrug-resistant (MDR) strains R18.0877 and R18.1656 were compared, revealing genetic differences.

Purpose of the Study:

  • To identify the genetic basis for differing antimicrobial resistance levels in closely related Salmonella Goldcoast strains.
  • To characterize a newly identified plasmid-borne gene, ramAp, and its role in antimicrobial resistance.

Main Methods:

  • Genome sequencing and comparative analysis of two MDR Salmonella strains.
  • Identification and characterization of a plasmid-borne ramA homolog (ramAp).
  • Introduction of ramAp and IS Ecp1 into Escherichia coli to assess gene expression and drug susceptibility.

Main Results:

  • An extra plasmid-borne ramAp gene was identified on an IncHI2 plasmid in strain R18.0877.
  • RamAp shares high sequence identity with Klebsiella quasipneumoniae chromosomal ramA.
  • Introduction of ramAp and IS Ecp1 into E. coli elevated efflux pump gene expression and MICs to multiple antibiotics.
  • RamAp activates existing efflux pump systems, reducing drug susceptibility and acting as an auxiliary antimicrobial resistance determinant.

Conclusions:

  • The plasmid-encoded ramAp gene is a novel auxiliary antimicrobial resistance determinant.
  • RamAp can be mobilized and expressed, potentially spreading via IncHI2 plasmids globally.
  • The interspecific conservation and potential for transmission of ramAp are significant concerns for the emergence of antimicrobial resistance.

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