Abstract
Resistance to the last treatment option for gonorrhoea, ceftriaxone is a major public health concern globally, which poses a serious threat to the currently recommended ceftriaxone monotherapy. We elucidate the emergence, evolution and temporal spread of ceftriaxone-resistant gonococcal strains in China, using whole-genome sequencing of 357 ceftriaxone-resistant isolates from eight provinces during 2002-2022. We describe distinct differences between ceftriaxone-resistant gonococcal strains in China and global isolates. The resistance levels for the 357 isolates for cefixime, azithromycin, ciprofloxacin, benzylpenicillin, tetracycline, and spectinomycin were 92.4%, 17.0%, 100%, 84.9%, 92.7%, and 0.8%, respectively. Before 2019, ceftriaxone-resistant isolates in China mainly harboured non-mosaic penA alleles like penA-13, penA-12, penA-18 or mosaic penA-10. From 2019, ceftriaxone-resistant isolates with mosaic penA-60.001 increased rapidly, becoming the dominant penA allele. Meanwhile, penA-60.001 was horizontally transferred from MLST ST1903 strains to strains of other MLST STs that were prevalent in China. Notably, the MLST ST7365 isolates with penA-60.001 allele had higher ceftriaxone MICs than isolates of the typical ST1903 FC428 clone. This may be attributed to a main clade of MLST ST7365 strains in China exhibiting elevated ceftriaxone MICs, and the temporal phylogeny showed this clade emerged around 1994. In summary, we reveal the unique genomic and evolutionary patterns of ceftriaxone-resistant gonococcal strains in China, and the 357 not previously reported isolates substantially increase the number of global ceftriaxone-resistant isolates. Our results suggest potential evolutionary pathways and directions of ceftriaxone-resistant strains, and provide valuable data for examining genomic epidemiology, antimicrobial resistance determinants and formulating strategies for surveillance and interventions.