We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evolution, persistence, and host adaption of a gonococcal AMR plasmid that emerged in the pre-antibiotic era.
- Authors
Yee, Wearn-Xin; Yasir, Muhammad; Turner, A. Keith; Baker, David J.; Cehovin, Ana; Tang, Christoph M.
- Abstract
Plasmids are diverse extrachromosomal elements significantly contributing to interspecies dissemination of antimicrobial resistance (AMR) genes. However, within clinically important bacteria, plasmids can exhibit unexpected narrow host ranges, a phenomenon that has scarcely been examined. Here we show that pConj is largely restricted to the human-specific pathogen, Neisseria gonorrhoeae. pConj can confer tetracycline resistance and is central to the dissemination of other AMR plasmids. We tracked pConj evolution from the pre-antibiotic era 80 years ago to the modern day and demonstrate that, aside from limited gene acquisition and loss events, pConj is remarkably conserved. Notably, pConj has remained prevalent in gonococcal populations despite cessation of tetracycline use, thereby demonstrating pConj adaptation to its host. Equally, pConj imposes no measurable fitness costs and is stably inherited by the gonococcus. Its maintenance depends on the co-operative activity of plasmid-encoded Toxin:Antitoxin (TA) and partitioning systems rather than host factors. An orphan VapD toxin encoded on pConj forms a split TA with antitoxins expressed from an ancestral co-resident plasmid or a horizontally-acquired chromosomal island, potentially explaining pConj's limited distribution. Finally, ciprofloxacin can induce loss of this highly stable plasmid, reflecting epidemiological evidence of transient local falls in pConj prevalence when fluoroquinolones were introduced to treat gonorrhoea. Author summary: Plasmids are extrachromosomal elements that disseminate antimicrobial resistance (AMR) among bacteria. Neisseria gonorrhoeae is a leading cause of sexually transmitted disease and a concern due to increasing AMR. It contains a restricted repertoire of plasmids, including a conjugative plasmid, pConj, which disseminates plasmid-mediated AMR. We show that, in contrast to broad host range plasmids, pConj is largely restricted to and adapted to N. gonorrhoeae, and has been remarkably conserved since it first emerged over 80 years ago. pConj is highly persistent, with no plasmid loss detected after 160 generations under standard laboratory conditions. We were unable to identify any chromosomal gene to account for the success of pConj. Instead, the lack of fitness costs and co-operative effects of maintenance systems result in its stable inheritance. Of note, pConj harbours an orphan VapD toxin that can be neutralised by VapX antitoxins expressed by a co-resident plasmid; this potential 'split' toxin:antitoxin system allows exquisite association of pConj with the gonococcus. Finally, we show that ciprofloxacin can induce pConj loss, mirroring the reduction in pConj carriage in the gonococcal population following introduction of this antibiotic for gonorrhoea, and paving the way for approaches to eliminate plasmid-mediated AMR in this important human pathogen.
- Subjects
PLASMIDS; SEXUALLY transmitted diseases; NEISSERIA gonorrhoeae; GONORRHEA; DRUG resistance in microorganisms; ANTITOXINS
- Publication
PLoS Genetics, 2023, Vol 19, Issue 5, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1010743