PenA Alleles Associated With Gonococcal Ceftriaxone Resistance in Cambodia, China, and Vietnam.

Abstract

The global dissemination of ceftriaxone-resistant Neisseria gonorrhoeae, primarily associated with mosaic penA alleles, threatens the efficacy of ceftriaxone therapy. While the FC428 clone and its associated penA allele 60.001 are well-documented, data on other emerging resistance-conferring alleles in high-burden regions remain limited. This study characterizes the penA alleles associated with ceftriaxone resistance in Cambodia, China, and Vietnam. Publicly available and novel genomes of N. gonorrhoeae isolates from Cambodia, China, and Vietnam with decreased ceftriaxone susceptibility (minimum inhibitory concentration [MIC] ≥ 0.125 mg/L) were analyzed. Multi-locus sequence types and penA alleles were assigned using PubMLST and BIGSdb and a core-genome neighbor-joining phylogenetic tree was constructed. To address selection bias, all isolates with reduced susceptibility from Hangzhou, China (2015-2022), were also analyzed for penA alleles using the NG-STAR method. Analysis of 236 genomes revealed that ceftriaxone resistance (MIC > 0.125 mg/L) was predominantly associated with penA alleles 60.001 (n = 145) and 237.001 (n = 70), which formed 2 major phylogenetic clades. All resistance-conferring alleles contained the A311 V polymorphism. PenA 60.001 was linked to multiple sequence types (STs), including FC428-associated ST1903 and endemic STs like ST8123 and ST8130. PenA 237.001 was almost exclusively found in Vietnam, primarily in ST1901. Analysis of the unbiased Hangzhou dataset (n = 132) confirmed that high-level resistance (MIC = 0.5-1 mg/L) was exclusively linked to penA 60.001. Ceftriaxone resistance in the Asia Pacific region is primarily driven by penA 60.001 and 237.001 along with related alleles harboring the A311 V polymorphism. The concerning acquisition of these alleles by successful endemic lineages enhances their potential for local and international spread.