Emergence of ceftriaxone-resistant Neisseria gonorrhoeae through horizontal gene transfer among Neisseria spp

Objectives: It has been suggested that the emergence of ceftriaxone-resistant strains of Neisseria gonorrhoeae involves the incorporation of the penA gene from commensal Neisseria spp. that are resistant to ceftriaxone. However, the mechanism of this mosaic penA generation is unknown.

Methods: We obtained 10 strains of commensal Neisseria spp. showing ceftriaxone MIC >0.5 mg/L. The similarity of the penA gene region of these commensal Neisseria spp. strains and some ceftriaxone-resistant N. gonorrhoeae strains was investigated. To obtain transformants, commensal Neisseria spp., Neisseria lactamica, gDNA was used as donor DNA and a N. gonorrhoeae strain as the recipient.

Results: The sequence similarity in certain regions of penA-murE between some of the commensal Neisseria spp. strains and the N. gonorrhoeae FC428 strain was very high. The sequence of these regions was very similar among some ceftriaxone-resistant strains of Neisseria spp. The PenA of the transformants matched the full PenA 60 of the original FC428 strain. Furthermore, our findings indicated that the source of resistance could have been a penA fragment derived from Neisseria spp. that originally carried the same sequence.

Conclusions: We suggest that FC428 developed ceftriaxone resistance by acquiring part of the penA-murE gene region from N. lactamica through horizontal gene transfer. The ceftriaxone-resistant N. lactamica shown here may also have emerged by acquiring part of penA from other Neisseria spp. From this work, our data provide insights into the understanding of the mechanism underlying the evolution of drug-resistant gonorrhea-causing strains.