Horizontal Gene Transfer of Fluoroquinolone Resistance-Conferring Genes From Commensal Neisseria to Neisseria gonorrhoeae: A Global Phylogenetic Analysis of 20,047 Isolates

Abstract

Antimicrobial resistance in <i>Neisseria gonorrhoeae</i> is an important global health concern. The genetically related commensal <i>Neisseria</i> act as a reservoir of resistance genes, and horizontal gene transfer (HGT) has been shown to play an important role in the genesis of resistance to cephalosporins and macrolides in <i>N. gonorrhoeae</i>. In this study, we evaluated if there was evidence of HGT in the genes <i>gyrA/gyrB</i> and <i>parC/parE</i> responsible for fluoroquinolone resistance. Even though the role of <i>gyrB</i> and <i>parE</i> in quinolone resistance is unclear, the subunits <i>gyrB</i> and <i>parE</i> were included as zoliflodacin, a promising new drug to treat <i>N. gonorrhoeae</i> targets the <i>gyrB</i> subunit. We analyzed a collection of 20,047 isolates; 18,800 <i>N. gonorrhoeae</i>, 1,238 commensal <i>Neisseria</i> spp., and nine <i>Neisseria meningitidis</i>. Comparative genomic analyses identified HGT events in genes, <i>gyrA</i>, <i>gyrB</i>, <i>parC</i>, and <i>parE</i>. Recombination events were predicted in <i>N. gonorrhoeae</i> and <i>Neisseria</i> commensals. <i>Neisseria lactamica</i>, <i>Neisseria macacae</i>, and <i>Neisseria mucosa</i> were identified as likely progenitors of the HGT events in <i>gyrA</i>, <i>gyrB</i>, and <i>parE</i>, respectively.