Sudden emergence of a Neisseria gonorrhoeae clade with reduced susceptibility to extended-spectrum cephalosporins, Norway

Abstract

Neisseria gonorrhoeae multilocus sequence type (ST)-7827 emerged in a dramatic fashion in Norway in the period 2016-2018. Here, we aim to shed light on the provenance and expansion of this ST. ST-7827 was found to be polyphyletic, but the majority of members belonged to a monophyletic clade we termed PopPUNK cluster 7827 (PC-7827). In Norway, both PC-7827 and ST-7827 isolates were almost exclusively isolated from men. Phylogeographical analyses demonstrated an Asian origin of the genogroup, with multiple inferred exports to Europe and the USA. The genogroup was uniformly resistant to fluoroquinolones, and associated with reduced susceptibility to both azithromycin and the extended-spectrum cephalosporins (ESCs) cefixime and ceftriaxone. From a genetic background including the penA allele 13.001, associated with reduced ESC susceptibility, we identified repeated events of acquisition of porB alleles associated with further reduction in ceftriaxone susceptibility. Transmission of the strain was significantly reduced in Norway in 2019, but our results indicate the existence of a recently established global reservoir. The worrisome drug-resistance profile and rapid emergence of PC-7827 calls for close monitoring of the situation.

Keywords: Neisseria gonorrhoeae; antimicrobial resistance; disease outbreaks; genomic epidemiology; phylogeography; transmission.

Fig. 1.

Overview of PC-7827 incidence and genomic properties. (a) Incidence of PC-7827 among culture-positive N. gonorrhoeae cases in relation to the total number of cultured cases during 2016–2019 in Norway (left). Age distribution of ST-7827 cases in Norway, Spain and Canada (right). (b) Pairwise median SNP-distances within ST-7827, PC-7827 and the recently emerged outbreak clade. Numbers above the dotted lines refer to median pairwise SNP-distance. (c) Annotated recombination-corrected genome-based phylogeny of 410 ST-7827 and PC-7827 genomes. The horizontal dotted line highlights the split between PC-7827 and unrelated ST-7827 genomes. An ST-1901 member was used as an outgroup. NOR, Norway; EUR, Europe; OCE, Oceania; E-Asia, East Asia; CEF, cefixime; CRO, ceftriaxone; AZM, azithromycin. porB specifies the presence of both mutations G120K and A121. The inset figure represents a zoomed-in dated phylogeny of the outbreak clade.

Fig. 2.

Phylogeographical inference. (a) Estimated geographical locations of PC-7827 mapped on a midpoint-rooted maximum-likelihood phylogeny from PhyML. To make the tree easier to read, some of the deeper branches were removed and one long branch was shortened (indicated by a red triangle). The full image is included in Fig S2. (b) Box plot summarizing the estimated number of transition events between East Asia and the rest of the world (RoW) over 1000 simmap simulations.

Fig. 3.

Reconstruction of temporal evolution and transmission patterns in the European outbreak. (a) Dated phylogeny of the European outbreak generated with BactDating. Node bars indicate 95 % highest posterior density intervals. (b) Heatmap ordered after the phylogeny showing the posterior probability of direct transmissions between each pair of patients, calculated as the fraction of the transmission trees where the pair is directly connected. (c) Similar heatmap showing the mean number of intermediate individuals between each pair of patients over all the transmission trees.