Abstract
Plasmids are vehicles for horizontal gene transfer between bacteria, and in Neisseria gonorrhoeae plasmids can mediate high-level antimicrobial resistance (AMR). Using genomic and phylogenetic analyses, we show that plasmids are widespread in a collection of 3724 gonococcal isolates from 56 countries, and characterized the conjugative, β-lactamase and cryptic plasmids. We found that variants of the conjugative plasmid (which can mediate tetracycline resistance) and the β-lactamase plasmid expressing TEM-135 are associated with distinct gonococcal lineages. Furthermore, AMR plasmids are significantly more prevalent in gonococci from less wealthy countries, highlighting the need for further studies. More than 94% of gonococci possess the cryptic plasmid, with its absence correlated with the presence of a novel chromosomal type IV secretion system. Our results reveal the extent of plasmid-mediated AMR in the gonococcus, particularly in less wealthy countries, where diagnostic and therapeutic options can be limited, and highlight the risk of their global spread.
Highlights
Gonococcal antimicrobial resistance (AMR) determinants are either chromosomally or plasmid-encoded [2], with recent research largely focusing on mechanisms of chromosomally mediated AMR, such as mosaic penA alleles [4]
We demonstrate that gonococcal AMR plasmids are prevalent in low- and middle-income countries (LMICs), with this previously unrecognized epidemic of plasmid-mediated AMR highlighting the need for further characterization of gonococcal plasmids worldwide
Of particular concern is reduced susceptibility to third-generation cephalosporins, which are the mainstay of treatment [2], with recent research focused on chromosomally mediated AMR [2, 4]
Summary
Gonococcal AMR determinants are either chromosomally or plasmid-encoded [2], with recent research largely focusing on mechanisms of chromosomally mediated AMR, such as mosaic penA alleles [4]. The 2 AMR plasmids were first reported in gonococci in 1970s and 1980s [5], respectively, and had profound effects on the treatment of gonorrhea, resulting in a decreased use of benzyl penicillin and tetracycline. We propose a nomenclature for gonococcal plasmids, with the prefix p followed by an abbreviation for each plasmid (ie, pConj for the conjugative, pbla for the β-lactamase, and pCryp for the cryptic plasmid). Several pbla have been isolated, all of which carry the TEM β-lactamase (blaTEM) and are derived from the prototypical Asia plasmid (7.4 kb) [8,9,10]. While chromosomal AMR genes, such as mosaic penA alleles, can lead to resistance against cephalosporins [4], plasmid-mediated AMR continues to pose a significant threat. We demonstrate that gonococcal AMR plasmids are prevalent in low- and middle-income countries (LMICs), with this previously unrecognized epidemic of plasmid-mediated AMR highlighting the need for further characterization of gonococcal plasmids worldwide
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