Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study (original) (raw)
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Open Forum Infectious Diseases
Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae (Ng) to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia (GA), USA during 2017-2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro-and-extragenital gonococcal (UGI) isolates (n = 110) collected in Fulton County, GA during 2017-2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the pop...
PeerJ, 2015
Neisseria gonorrhoeae is the causative agent of gonorrhea, a sexually transmitted infection (STI) of major importance. As a result of antibiotic resistance, there are now limited options for treating patients. We collected draft genome sequence data and associated metadata data on 76 N. gonorrhoeae strains from around the globe and searched for known determinants of antibiotics resistance within the strains. The population structure and evolutionary forces within the pathogen population were analyzed. Our results indicated a cosmopolitan gonoccocal population mainly made up of five subgroups. The estimated ratio of recombination to mutation (r/m = 2.2) from our data set indicates an appreciable level of recombination occurring in the population. Strains with resistance phenotypes to more recent antibiotics (azithromycin and cefixime) were mostly found in two of the five population subgroups.
Sexually Transmitted Diseases, 2021
Resistant Neisseria gonorrhoeae Working Group Background: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations to various antibiotics continues to rise in the United States and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. Methods: Neisseria gonorrhoeae isolates collected from the US Gonococcal Isolate Surveillance Project in 2018 (n = 1479) were sequenced and characterized. Whole-genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. Results: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. Conclusions: Characterization of this 2018 Gonococcal Isolate Surveillance Project genomic data set, which is the largest US whole-genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring.
Journal of Clinical Microbiology, 2014
39 A large-scale, whole-genome comparison of Canadian N. gonorrhoeae isolates with 40 high-level cephalosporin minimum inhibitory concentrations (MICs) was used to 41 demonstrate a genomic epidemiology approach to investigate strain relatedness and 42 dynamics. Although current typing methods have been very successful in tracing short 43 chain transmission of gonorrhoeal disease, investigating the temporal evolutionary 44 relationships and geographical dissemination of highly clonal lineages requires 45 enhanced resolution only available through whole-genome sequencing (WGS). 46 Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. 47 While some N. gonorrhoeae multi-antigen (NG-MAST) sequence types (ST) agreed 48 with specific phylogenomic clades or sub-clades, other STs and closely related groups 49 of STs were widely distributed among clades. Decreased susceptibility to extended 50 spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in 51 Canada during the 1990s with a variety of non-mosaic penA alleles, followed in 52 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with 53 the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were 54 associated with penA mosaic X, XXXV, XXXIV; and non-mosaic XII and XIII 55 alleles. ESC-DS with co-resistance to azithromycin was observed in 5 strains with 56 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline 57 and analysis tools are streamlined, WGS can provide a more thorough understanding 58 of strain dynamics, facilitate epidemiological studies to better resolve social networks, 59 and improve surveillance to optimize treatment for gonorrhoeal infections. 60 61 decreased membrane permeability and contribute to decreased susceptibility towards 86 157 De Novo Assembly 158
Microorganisms
The aim of this work was to study the genetic diversity of the gonococcal genetic island (GGI) responsible for the type IV secretion system (T4SS) and the association of a functionally active GGI with antimicrobial resistance. An analysis of the GGI in a sample of 14,763 genomes of N. gonorrhoeae isolates from the Pathogenwatch database collected in 1996–2019 from 68 countries was performed. A model of GGI’s genetic diversity that divides the global gonococcal population into fifty-one GGI clusters and three GGI superclusters based on the allele type of the traG gene and substitutions of the atlA and ych genes for eppA and ych1 has been proposed, reflecting differences among isolates in the T4SS functionality. The NG-MAST and MLST typing schemes (with accuracies of 91% and 83%, respectively) allowed the determination of both the presence of a GGI and the GGI cluster and, correspondingly, the structure of the GGI and the ability to secrete DNA. A statistically significant difference ...
The Journal of Infectious Diseases
Background Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is a globally prevalent sexually transmitted infection. The dynamics of gonococcal population biology have been poorly defined due to a lack of resolution in strain typing methods. Methods In this study, we assess how the core genome can be used to improve our understanding of gonococcal population structure compared with current typing schemes. Results A total of 1668 loci were identified as core to the gonococcal genome. These were organized into a core genome multilocus sequence typing scheme (N gonorrhoeae cgMLST v1.0). A clustering algorithm using a threshold of 400 allelic differences between isolates resolved gonococci into discrete and stable core genome groups, some of which persisted for multiple decades. These groups were associated with antimicrobial genotypes and non-overlapping NG-STAR and NG-MAST sequence types. The MLST-STs were more widely distributed among core genome groups. Conclusions Clusterin...
The Journal of infection, 2016
Antimicrobial resistance (AMR) threatens our ability to treat the sexually transmitted bacterial infection gonorrhoea. The increasing availability of whole genome sequence (WGS) data from Neisseria gonorrhoeae isolates, however, provides us with an opportunity in which WGS can be mined for AMR determinants. Chromosomal and plasmid genes implicated in AMR were catalogued on the PubMLST Neisseria database (http://pubmlst.org/neisseria). AMR genotypes were identified in WGS from 289 gonococci for which MICs against several antimicrobial compounds had been determined. Whole genome comparisons were undertaken using whole genome MLST (wgMLST). Clusters of isolates with distinct AMR genotypes were apparent following wgMLST analysis consistent with the occurrence of genome wide genetic variation. This included the presence of the gonococcal genetic island (GGI), a type 4 secretion system shown to increase recombination and for which possession was significantly associated with AMR to multip...
Journal of Antimicrobial Chemotherapy, 2020
Objectives Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015–16 across all five macroregions in Brazil. Methods A total of 548 gonococcal isolates cultured across Brazil in 2015–16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n = 158) and the 2016 WHO reference strains (n = 14) were included in the analysis. Results We found 302, 68 and 214 different NG-MAST, ...
Journal of Antimicrobial Chemotherapy, 2019
Our aim was to describe the molecular epidemiology and antimicrobial resistance determinants of isolates of Neisseria gonorrhoeae with decreased susceptibility and resistance to extended-spectrum cephalosporins (ESCs) in Argentina in 2011-16. Methods: Gonococcal isolates (n"158) with decreased susceptibility and resistance to ESCs collected in 2011-16 across Argentina were subjected to WGS and antimicrobial susceptibility testing for six antimicrobials. Results: In total, 50% of the isolates were resistant to cefixime, 1.9% were resistant to ceftriaxone, 37.3% were resistant to azithromycin and 63.9% of the isolates showed an MDR phenotype. Resistance and decreased susceptibility to ESCs was mainly associated with isolates possessing the mosaic penA-34.001, in combination with an mtrR promoter A deletion, and PorB1b amino acid substitutions G120K/A121N. Phylogenetic analysis revealed two main clades of circulating strains, which were associated with the N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 and closely related STs, and characterized by a high prevalence rate, wide geographical distribution and temporal persistence. Conclusions: N. gonorrhoeae isolates with decreased susceptibility and resistance to ESCs in Argentina have emerged and rapidly spread mainly due to two clonal expansions after importation of one or two strains, which are associated with the international MDR NG-MAST ST1407 clone. The identification of the geographical dissemination and characteristics of these predominant clones may help to focus action plans and public health policies to control the spread of ESC resistance in Argentina. Dual antimicrobial therapy (ceftriaxone plus azithromycin) for gonorrhoea needs to be considered in Argentina.
2021
Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 genogroup isolates have been associated with reduced azithromycin susceptibility (AZMrs) and show evidence of clonal expansion in the U.S. Here we analyze a global collection of ST-9363 genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 genogroup is inferred to have originated from Asia in the mid-19th century; we estimate the three modern lineages emerged from Europe in the late 1970s to early 1980s. The European lineage appears to have emerged and expanded from around 1986 to 1998, spreading into North America and Oceania in the mid-2000s with multiple introductions, along with multiple secondary reintroductions into Europe. Our results suggest two separate acquisition events of mosaic mtrR and mtrR promoter alleles: first d...