Mosaic Drug Efflux Gene Sequences from Commensal

Area of Science:

• Microbiology
• Genetics
• Antimicrobial Resistance

Background:

• Neisseria gonorrhoeae is a significant cause of sexually transmitted infections.
• Antibiotic resistance in N. gonorrhoeae, particularly to macrolides like azithromycin, is a growing public health concern.
• The mtr locus, encoding the MtrC-MtrE efflux pump and its repressor MtrR, is crucial for macrolide resistance.

Purpose of the Study:

• To investigate the genetic mechanisms underlying low-level azithromycin resistance in Neisseria gonorrhoeae isolates.
• To understand the role of horizontal gene transfer from commensal Neisseria species in conferring antibiotic resistance.

Main Methods:

• Whole-genome sequencing and bioinformatic analysis of N. gonorrhoeae isolates.
• Genetic analyses to assess the functional impact of identified genetic changes.
• Linkage disequilibrium mapping to identify regions associated with resistance.

Main Results:

• Isolates with low-level azithromycin resistance acquired mosaic DNA sequences from commensal Neisseria spp.
• These acquired sequences altered the mtr locus, increasing transcription of the mtrCDE genes and MtrD function.
• Significant epistatic effects were observed, collectively leading to decreased susceptibility to azithromycin and other MtrCDE substrates.

Conclusions:

• Horizontal gene transfer between Neisseria species is a key driver of antibiotic resistance evolution in N. gonorrhoeae.
• Understanding these genetic mechanisms is vital for accurate detection of resistance markers.
• The findings have implications for the efficacy of current and future antibiotic treatment regimens for gonorrhea.