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]

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Summary

Introduction

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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