Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey

Abstract

SummaryBackgroundTraditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data.MethodsWe carried out an observational study, in which we sequenced isolates taken from patients with gonorrhoea from the European Gonococcal Antimicrobial Surveillance Programme in 20 countries from September to November, 2013. We also developed a web platform that we used for automated antimicrobial resistance prediction, molecular typing (N gonorrhoeae multi-antigen sequence typing [NG-MAST] and multilocus sequence typing), and phylogenetic clustering in conjunction with epidemiological and phenotypic data.FindingsThe multidrug-resistant NG-MAST genogroup G1407 was predominant and accounted for the most cephalosporin resistance, but the prevalence of this genogroup decreased from 248 (23%) of 1066 isolates in a previous study from 2009–10 to 174 (17%) of 1054 isolates in this survey in 2013. This genogroup previously showed an association with men who have sex with men, but changed to an association with heterosexual people (odds ratio=4·29). WGS provided substantially improved resolution and accuracy over NG-MAST and multilocus sequence typing, predicted antimicrobial resistance relatively well, and identified discrepant isolates, mixed infections or contaminants, and multidrug-resistant clades linked to risk groups.InterpretationTo our knowledge, we provide the first use of joint analysis of WGS and epidemiological data in an international programme for regional surveillance of sexually transmitted infections. WGS provided enhanced understanding of the distribution of antimicrobial resistance clones, including replacement with clones that were more susceptible to antimicrobials, in several risk groups nationally and regionally. We provide a framework for genomic surveillance of gonococci through standardised sampling, use of WGS, and a shared information architecture for interpretation and dissemination by use of open access software.FundingThe European Centre for Disease Prevention and Control, The Centre for Genomic Pathogen Surveillance, Örebro University Hospital, and Wellcome.

Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017

“…The isolate (F89) harboured a mosaic penA XXXIV allele with an additional A501P alteration in PBP2 and belonged to the internationally spread MDR NG-MAST ST1407 clone [17]. Since 2010, F89 has only been reported in Spain [18] and does not appear to have spread further, which is likely due to a decreased biological fitness of F89 [19].…”

Genomic surveillance ofNeisseria gonorrhoeaein the Philippines, 2013–2014

“…We also contextualized our isolates with 1054 genomes from 20 countries collected in 2013 by a European survey. 15 Notably, the genome of strain 14ARS_VSM0347 isolated from a female on 25/04/2014 in the Philippines was highly similar to that of ECDC_GC_088 isolated from a male on 31/12/2013 in Norway ( Figure 3B), with no SNP differences found in the Pathogenwatch core genome (1542 genes). One SNP was identified in the reference-based alignment of the two pseudogenomes, confirming that these two genomes are highly similar.…”

“…To contextualize the genomes from this study with public global genomes we combined them with two surveys available on Pathogenwatch, a European survey of 1054 genomes 15 and a global survey of 419 genomes. 16 The outputs from Pathogenwatch (tree, genotyping and AMR predictions) together with the metadata collected from the sentinel sites were visualised with Microreact.…”

“…The Philippine genomes were contextualized with two recently published collections 15,16 available in Pathogenwatch. A recent global collection of 419 genomes from 58 countries (including the Philippines) defined two major lineages with different evolutionary strategies.…”

Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae

“…Antimicrobial resistance in this pathogen is of great public health concern and there have recently been an increasing number of publications aimed at analysing its transmission and the evolution of genetic determinants of antimicrobial resistance using high throughput shortread sequencing [1][2][3][4] . However, Single Molecule Real-Time (SMRT) PacBio sequencing provides deeper information about microbial genomes, including data on DNA modification, mainly methylation in the form of 6mA, 5mC or 4mC.…”