Abstract
SummaryObjectivesAntimicrobial resistance (AMR) threatens our ability to treat the sexually transmitted bacterial infection gonorrhoea. The increasing availability of whole genome sequence (WGS) data from Neisseria gonorrhoeae isolates, however, provides us with an opportunity in which WGS can be mined for AMR determinants.MethodsChromosomal and plasmid genes implicated in AMR were catalogued on the PubMLST Neisseria database (http://pubmlst.org/neisseria). AMR genotypes were identified in WGS from 289 gonococci for which MICs against several antimicrobial compounds had been determined. Whole genome comparisons were undertaken using whole genome MLST (wgMLST).ResultsClusters of isolates with distinct AMR genotypes were apparent following wgMLST analysis consistent with the occurrence of genome wide genetic variation. This included the presence of the gonococcal genetic island (GGI), a type 4 secretion system shown to increase recombination and for which possession was significantly associated with AMR to multiple antimicrobials.ConclusionsEvolution of the gonococcal genome occurs in response to antimicrobial selective pressure resulting in the formation of distinct N. gonorrhoeae populations evidenced by the wgMLST clusters seen here. Genomic islands offer selective advantages to host bacteria and possession of the GGI may, not only facilitate the spread of AMR in gonococcal populations, but may also confer fitness advantages.
Highlights
Neisseria gonorrhoeae, the aetiological agent of the sexually transmitted disease gonorrhoea, annually causes an estimated 108 million cases globally.[1]
Gonococci become resistant to antibiotics through spontaneous mutation and/or horizontal genetic transfer (HGT) with resistance conferred through all known mechanisms including antimicrobial inactivation, antimicrobial target alteration as well as increased export and decreased uptake of antimicrobial compounds.[2]
Increased export of antimicrobial compounds may occur through alterations of the mtrR efflux pump repressor gene and/or its associated promoter resulting in overexpression of the MtrCDE efflux pump,[8,9] while decreased antimicrobial uptake occurs through alteration of the major outer membrane protein PorB encoded by porB1b
Summary
The aetiological agent of the sexually transmitted disease gonorrhoea, annually causes an estimated 108 million cases globally.[1]. Gonorrhoea may lead to increased HIV transmission.[2] While effective treatment of gonorrhoea is a priority for public health globally, treatment options have diminished as N. gonorrhoeae strains have developed resistance to multiple classes of antibiotics.[3]. Gonococci become resistant to antibiotics through spontaneous mutation and/or horizontal genetic transfer (HGT) with resistance conferred through all known mechanisms including antimicrobial inactivation, antimicrobial target alteration as well as increased export and decreased uptake of antimicrobial compounds.[2] For example, resistance to fluoroquinolones, which inhibit the action of topoisomerase enzymes involved in DNA replication, occurs through amino acid alterations in the chromosomal DNA gyrase gene, gyrA and/or the DNA topoisomerase gene, parC.[4] The penicillin binding proteins 1 and 2 (PBP1 and PBP2) encoded by ponA and penA respectively are essential in the final stages of peptidoglycan synthesis involved in cell wall assembly. Antimicrobial inactivation may result from plasmid-mediated beta-lactamases and/or tetM genes which facilitate penicillin and/or tetracycline resistance.[11,12]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call