Dataset Information

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.

SUBMITTER: Osnes MN

PROVIDER: S-EPMC8116678 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Sudden emergence of a <i>Neisseria gonorrhoeae</i> clade with reduced susceptibility to extended-spectrum cephalosporins, Norway.

Osnes Magnus N MN Didelot Xavier X Korne-Elenbaas Jolinda de J Alfsnes Kristian K Brynildsrud Ola B OB Syversen Gaute G Nilsen Øivind Jul ØJ De Blasio Birgitte Freiesleben BF Caugant Dominique A DA Eldholm Vegard V

Microbial genomics 20201117 12

<i>Neisseria gonorrhoeae</i> 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 genogrou ...[more]

PMID: 33200978

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Project description:BACKGROUND: The spread of Neisseria gonorrhoeae strains with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins is a major public health problem. While much work has been performed internationally, little is known about the genetics or molecular epidemiology of N. gonorrhoeae isolates with reduced susceptibility to extended-spectrum cephalosporins in the United States. The majority of N. gonorrhoeae infections are diagnosed without a live culture. Molecular tools capable of detecting markers of extended-spectrum cephalosporin resistance are needed. METHODS: Urethral N. gonorrhoeae isolates were collected from 684 men at public health clinics in California in 2011. Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime and azithromycin were determined by Etest and categorized according to the U.S. Centers for Disease Control 2010 alert value breakpoints. 684 isolates were screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive isolates were subjected to DNA sequencing of their penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity of the screening RTPCR in detecting isolates with alert value extended-spectrum cephalosporin MICs, the primers were modified to selectively amplify the mosaic XXXIV penA allele. RESULTS: Three mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study. CONCLUSION: N. gonorrhoeae isolates with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins are currently circulating in California. Isolates with the same NG-MAST ST, penA allele and extended-spectrum cephalosporin MICs have caused treatment failures elsewhere. The RTPCR assay presented here may be useful for the detection of N. gonorrheoae isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs in settings where antimicrobial susceptibility testing is unavailable. In an era of increasing antimicrobial resistance and decreasing culture capacity, molecular assays capable of detecting extended-spectrum cephalosporin of resistance are essential to public health.

Project description:The recent emergence of Neisseria gonorrhoeae strains with decreased susceptibility to extended-spectrum cephalosporins is a major concern globally. We sequenced the genome of an N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolate (SM-3) with decreased susceptibility and resistance to oral extended-spectrum cephalosporins. The isolate was cultured in 2008 in San Francisco, CA, and possessed mosaic penA allele XXXIV, which is associated with an international clone that possesses decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins globally. The genome sequence of strain NCCP11945 was used as a scaffold, and our assembly resulted in 91 contigs covering 2,029,064 bp (91%; >150× coverage) of the genome. Numerous instances of suspected horizontal genetic transfer events with other Neisseria species were identified, and two genes, opa and txf, acquired from nongonococcal Neisseria species, were identified. Strains possessing mosaic penA alleles (n = 108) and nonmosaic penA alleles (n = 169) from the United States and Europe (15 countries), cultured in 2002 to 2009, were screened for the presence of these genes. The opa gene was detected in most (82%) penA mosaic-containing isolates (mainly from 2007 to 2009) but not in any penA nonmosaic isolates. The txf gene was found in all strains containing opa but also in several (18%) penA nonmosaic strains. Using opa and txf as genetic markers, we identified a strain that possesses mosaic penA allele XXXIV, but the majority of its genome is not genetically related to strain SM-3. This implies that penA mosaic allele XXXIV was transferred horizontally. Such isolates also possessed decreased susceptibility and resistance to oral extended-spectrum cephalosporins. These findings support that genetic screening for particular penA mosaic alleles can be a valuable method for tracking strains with decreased susceptibility as well as resistance to oral extended-spectrum cephalosporins worldwide and that screening using only NG-MAST may not be sufficient.

Project description:IntroductionNeisseria gonorrhoeae (Ng) has successively developed resistance to all previously recommended antimicrobial therapies, with ceftriaxone being the last option for monotherapy of gonorrhea. Global emergence and international spread of the FC428 clone derived mosaic penA-60 allele, associated with highlevel ceftriaxone minimum inhibitory concentrations (MICs) in non FC428 clone Ng lineages, has become an increasing concern. The penA-60 allele carrying Ng was first identified in the U.S. in Las Vegas, Nevada (2019; GCWGS-102723), with a multi-locus sequence type (MLST)-1901 strain, in a non FC428 clone Ng lineage, which is associated with a historically ceftriaxone susceptible core genogroup. Later in 2022, an allele genetically similar to penA-60, mosaic penA-237, was identified in the UK (H22-722) and France (F92) with high-level ceftriaxone MICs and both belonged to MLST-1901.MethodsIn this study, we assessed phylogenomic relatedness and antimicrobial resistance (AMR) determinant profiles of these three isolates with high-level ceftriaxone MICs among a global collection of 2,104 genomes belonging to the MLST-1901 core genome cluster group 31, which includes strains separated by a locus threshold of 200 or fewer differences (Ng_cgc_200). Recombination events in and around the penA coding region were catalogued and potential sources of inter species recombinant DNA were also inferred.ResultsThe global population structure of MLST-1901 core genogroup falls into 4 major lineages. Isolates GCWGS-10723, F92, and H22-722 clustered within Lineage 1, which was dominated by non-mosaic penA-5 alleles. These three isolates formed a clade within Lineage 1 that consisted of isolates from North America and southeast Asia. Neisseria subflava and Neisseria sicca were identified as likely progenitors of two independent recombination events that may have led to the generation of mosaic penA-60 and penA-237, within a possible non-mosaic penA-5 background.DiscussionsOur study suggests that there are multiple evolutionary pathways that could generate concerning mosaic penA alleles via homologous recombination of historically susceptible Ng lineages with Neisseria commensals. Enhanced surveillance of gonococcal strains and Neisseria commensals is crucial for understanding of the evolution of AMR, particularly in less-studied regions (e.g., Asia), where high-level ceftriaxone MICs and multi-drug resistance are more prevalent.

Dataset Information

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

Publications

Sudden emergence of a <i>Neisseria gonorrhoeae</i> clade with reduced susceptibility to extended-spectrum cephalosporins, Norway.

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