The recent introduction of mosaic mtr-carrying Neisseria gonorrhoeae lineages boosts local transmission

OBJECTIVES: Gonorrhoea, caused by Neisseria gonorrhoeae, is a significant public health challenge due to the rising incidence of antimicrobial resistant (AMR) strains. The Valencian Region, one of the top tourist destinations in Eastern Spain, has witnessed an increase of over 200% in the number of cases in recent years. Here, we aimed to investigate the impact of imported AMR lineages in shaping the local gonococcal population and generating sustained transmission events. METHODS: We analysed 1647 N. gonorrhoeae isolates collected in the Valencian Region between 2012 and 2024 with accompanying phenotypic antimicrobial susceptibility and epidemiological data. Genomic data was obtained through high-throughput sequencing and combined with 5894 genomes from national and international isolates. From these, information on typing and genetic AMR determinants was derived. Phylogenomic and statistical inference were used to investigate the local dynamics of this pathogen. RESULTS: Results revealed high levels of AMR, including 63.6% (n = 449/706) ciprofloxacin resistance, 17.7% (n = 195/1102) azithromycin resistance, and 8.4% (n = 66/783) reduced susceptibility or resistance to ceftriaxone. The two main circulating lineages were NG-STAR CC1615 and CC63, carrying 55.0% (n = 121/220) and 26.5% (n = 45/170) isolates with a mosaic mtr (mosaic mtrD and mtrR promoter), respectively. Phylodynamic analyses identified multiple introductions of AMR lineages into the region leading to sustained transmissions since the 1990s. These lineages significantly carried more isolates with mtr mosaics (OR = 4.17 [3.27-5.34]; p 1.26E-33) and phenotypic resistance to azithromycin (OR = 2.22 [1.60-3.06]; p 1.14E-06), among other antimicrobials. CONCLUSIONS: This study highlights the dynamic evolution and dissemination of AMR N. gonorrhoeae at the local level, highlighting the role of international mobility, sexual networks, and antibiotic usage in shaping resistance patterns. Enhanced genomic surveillance, with special monitoring of mosaic mtr-carrying lineages, together with targeted public health interventions, will be key to curb local and regional spread of resistant gonococcal strains.