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.

Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin

“…The clonal timed phylogenetic analysis of ST-9363 genogroup gonococci for a global collection of 1,978 isolates from 1996 to 2018 (Table S1) estimated a substitution rate of 4.752 x 10 -6 substitutions per site per year, (95% highest posterior density (HPD) ranging from 4.163 x 10 -6 to 4.933 x 10 -6 ), which was similar to previous estimates from other population level studies that included gonococcal isolates from a single or similar STs (Sánchez-Busó et al 2019;Osnes et al 2020;Osnes et al 2021). The time to the most recent common ancestor (tMRCA) of the entire ST-9363 genogroup was estimated to be in the mid-19th century (1853; 95% highest posterior density (HPD): [1833 -1883]).…”

“…Obtaining representative samples for the global ST-9363 gonococcal population is often a challenge. Convenient sampling by incorporating all available unique genomes from a genogroup along with the use of robust evolutionary models similar to this study and other genome-based gonococcal evolutionary analysis (Osnes et al 2020;Osnes et al 2021) are appropriate to estimate global evolutionary trends, although it might be inadequate for estimating incidence or prevalence of these strains. Our analyses performed on a down-sampled geographically balanced dataset largely identified the same evolutionary trends similar to the findings inferred using the full dataset.…”

“…Only isolates that belonged to the European and North American lineages were included in this analysis. The implementation and parameters chosen were similar as described previously (Osnes et al 2020). Briefly, for the generation time distribution (time from being infected to infecting others), two gamma distributions where considered, one which was estimated in an individual-based modelling study from a community of men who have sex with men (MSM) (Whittles et al 2019), which is called "prior 1" with shape 0.57 and scale 0.30, and a second distribution similar to prior 1 but penalizing transmissions in the incubation phase -"prior 2" with shape 1.20 and scale 0.14.…”

Emergence of a Neisseria gonorrhoeae clone with reduced cephalosporin susceptibility between 2014 and 2019 in Amsterdam, The Netherlands, revealed by genomic population analysis

“…When this strain emerged in Norway during 2016–18 it was associated with reduced susceptibility to cephalosporins and we now confirm that the same emergence has occurred in the Netherlands during the last 3 years. 12 Since recent isolates from other European countries are scarce, these results can only suggest circulation of this strain in other parts of Europe.…”

“…Isolates belonging to MLST1901/NG-MAST1407 with mosaic penA alleles were highly prevalent among strains with reduced susceptibility to ceftriaxone also, suggesting that tracking this strain is most important for monitoring emerging resistance. However, Osnes et al 12 recently reported the emergence of a strain with reduced susceptibility between 2016 and 2018 in Norway, belonging to MLST7827 and carrying a non-mosaic penA 13.001 allele with A501V mutation. They showed that this strain, with an alarming antimicrobial resistance profile, likely originated from Asia and potentially circulates in Europe.…”