Interspecific sources of resistance for Neisseria gonorrhoeae: Investigating horizontally transferred antimicrobial resistance markers

Antibiotic resistance is a growing public health crisis, limiting treatment options and increasing the burden of infectious diseases. Bacteria can rapidly gain resistance through mutations and horizontal gene transfer (HGT). Understanding these mechanisms is critical for developing strategies to mitigate resistance and preserve antibiotic efficiency. Neisseria gonorrhoeae, the causative agent of gonorrhea, has developed resistance to multiple antibiotics, and has only one remaining treatment option. Commensal species are constantly exposed to antibiotics in humans, and over time acquire resistant mutations that then transfer to pathogenic species through HGT. Investigating these exchanges can provide insight into how resistance evolves and spreads within the Neisseria genus. To explore HGT’s role in resistance evolution, we conducted phylogenetic and sequence analyses on 19 genes from 2,116 Neisseria isolates. We found phylogenetic evidence of HGT in nine genes and transferred regions in four: rpoB, mtrD, macA, and rplD, as well as mosaicism in penA. Additionally, we identified eight resistance-associated mutations across seven genes. While there was no direct overlap between HGT regions and known resistance markers, our findings support the role of commensal Neisseria as reservoirs for genetic variation. Given the rapid evolution of antibiotic resistance in N. gonorrhoeae, continued surveillance with larger datasets is essential to identifying emerging resistance determinants and understanding the selective pressures shaping bacterial adaptation.