Emergence of a cephalosporin reduced susceptible Neisseria gonorrhoeae clone between 2014-2019 in Amsterdam, the Netherlands, revealed by a genomic population analysis

Emerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of reduced susceptible and resistant strains. For the purpose of epidemiological surveillance, a genomic population analysis was performed on Ng isolates from Amsterdam with a focus on ceftriaxone reduced susceptible isolates. Whole genome sequences were obtained from 318 isolates from 2014-2019 from Amsterdam, the Netherlands. Isolates were typed according to the Multi-Locus Sequence Typing (MLST) scheme and resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch- and global MLST7827 isolates. The majority of ceftriaxone reduced susceptible isolates belonged to MLST7363, MLST1901 and MLST7827. MLST7363 and MLST1901 were dominant reduced susceptible strains from 2014-2016 although MLST7827 emerged and became dominant during 2017-2019. MLST7827 reduced susceptible isolates carried a non-mosaic penA gene with A501V mutation and porB G121K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch- and other European MLST7827 isolates. Ceftriaxone reduced susceptible MLST7827 isolates emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB G121K/A121D mutations was strongly associated with ceftriaxone reduced susceptibility. Genetic clustering of Dutch- and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Therefore, close monitoring of the spread of this strain with an alarming susceptibility profile is needed.