Global Resistance of Neisseria gonorrhoeae

When Theory Becomes Reality

David A. Lewis


Curr Opin Infect Dis. 2014;27(1):62-67. 

In This Article

Mechanisms of Gonococcal Resistance to Extended Spectrum Cephalosporins

In general, gonococci with reduced susceptibility/resistant to oral ESCs have multiple chromosomal mutations in the penA gene, which encodes for penicillin-binding protein 2 (PBP-2), the principal target of ESCs. The reduced susceptibility of these gonococci to ESCs appears to be due to conformational alteration of the β-lactam-binding pocket of PBP-2.[7] These mosaic penA genes are thought to result from the acquisition of substantial parts of the penA gene of commensal Neisseria species, which share the same anatomical niche as the gonococcus. In support of this view, molecular characterization of gonococcal mosaic penA genes has revealed considerable homology with the penA gene of other Neisseria species.[8,9] Given that commensal Neisseria species are more abundant in oro-pharyngeal than urethral/endocervical niches, it has also been hypothesized that horizontal transfer and recombination between these bacteria and the gonococcus is more likely to occur in the oro-pharynx. This concept highlights the importance of key populations, such as commercial sex workers (CSW) and men-who-have-sex-with-men (MSM), in the generation and transmission ESC-resistant N. gonorrhoeae.

There are several variations in mosaic PBP-2 structure and some gonococcal strains, which possess a mosaic penA gene, remain susceptible to ESCs.[8] Accordingly, researchers have looked for other genetic mutations that may account for the observed alterations in ESC susceptibility. Mutations in the gonococcal PBP-2 at amino acid position 501 (e.g. A501 V, A501T and A501P), which have not been found in commensal Neisseria species, appear to preferentially reduce susceptibility to ceftriaxone.[7,10,11]