| Summary: | Pathogenic <i>Neisseria gonorrhoeae</i> causes the sexually transmitted infection gonorrhea. <i>N. gonorrhoeae</i> has evolved high levels of antimicrobial resistance (AR) leading to therapeutic failures even in dual-therapy treatment with azithromycin and ceftriaxone. AR mechanisms can be acquired by genetic transfer from closely related species, such as naturally competent commensal <i>Neisseria</i> species. At present, little is known about the antimicrobial resistance profiles of commensal <i>Neisseria</i>. Here, we characterized the phenotypic resistance profile of four commensal <i>Neisseria</i> species (<i>N. lactamica</i>, <i>N. cinerea</i>, <i>N. mucosa</i>, and <i>N. elongata</i>) against 10 commonly used antibiotics, and compared their profiles to 4 <i>N. gonorrhoeae</i> strains, using disk diffusion and minimal inhibitory concentration assays. Overall, we observed that 3 of the 4 commensals were more resistant to several antibiotics than pathogenic <i>N. gonorrhoeae</i> strains. Next, we compared publicly available protein sequences of known AR genes, including penicillin-binding-protein 2 (PBP2) from commensals and <i>N. gonorrhoeae</i> strains. We found mutations in PBP2 known to confer resistance in <i>N. gonorrhoeae</i> also present in commensal <i>Neisseria</i> sequences. Our results suggest that commensal <i>Neisseria</i> have unexplored antibiotic resistance gene pools that may be exchanged with pathogenic <i>N. gonorrhoeae</i>, possibly impairing drug development and clinical treatment.
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