Population structure of<i>Neisseria gonorrhoeae</i>based on whole genome data and its relationship with antibiotic resistance

Ezewudo, Matthew; Joseph, Sandeep J.; Castillo-Ramírez, Santiago; Dean, Deborah; Rı́o, Carlos del; Didelot, Xavier; Dillon, Jo-Anne R.; Selden, Richard F.; Shafer, William M.; Turingan, Rosemary S.; Unemo, Magnus; Read, Timothy D.

doi:10.7717/peerj.806

Cited by 69 publications

(50 citation statements)

References 53 publications

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“…Clusters 5 and 6 included ST-1588 and ST-1893 isolates on longer branches indicative of diversity. FA1090 and MS11 were part of a large diverse group of isolates, some of which dating from the 1980s 14, 27…”

Section: Resultsmentioning

confidence: 99%

“…Isolates had been analysed for antimicrobial minimum inhibitory concentrations (MICs) to several antibiotics 13, 14. Short reads were obtained from the European Nucleotide Archive (ENA) and assembled de novo using VELVET in combination with VELVETOPTIMISER as previously described 18 .…”

Section: Methodsmentioning

confidence: 99%

“…For example, associations between resistance to the third generation cephalosporin, cefixime and possession of penA mosaic alleles have been identified in several WGS studies undertaken in N. gonorrhoeae 6, 13, 14. The PubMLST.org/neisseria website archives and annotates, at the time of writing, >7000 WGS data from multiple Neisseria species including N. gonorrhoeae 15 .…”

Section: Introductionmentioning

confidence: 99%

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Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance

Harrison

Clemence

Dillard

et al. 2016

Journal of Infection

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SummaryObjectivesAntimicrobial 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.MethodsChromosomal 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).ResultsClusters 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 multiple antimicrobials.ConclusionsEvolution of the gonococcal genome occurs in response to antimicrobial selective pressure resulting in the formation of distinct N. gonorrhoeae populations evidenced by the wgMLST clusters seen here. Genomic islands offer selective advantages to host bacteria and possession of the GGI may, not only facilitate the spread of AMR in gonococcal populations, but may also confer fitness advantages.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance

Harrison

Clemence

Dillard

et al. 2016

Journal of Infection

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“…These data suggest that CU and GU strains evolve under negative selection. Other sexually transmitted bacterial pathogens such as Neisseria gonorrhoeae and Chlamydia trachomatis also evolve under negative selection, with overall mean d N / d S ratios of 0.3184 and 0.4021, respectively [ 39 , 40 ]. These findings are in agreement with the neutral theory of molecular evolution, which postulates that selective fixation of neutral mutations by genetic drift is the major determinant behind species divergence [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains

et al. 2015

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BackgroundAlthough cutaneous ulcers (CU) in the tropics is frequently attributed to Treponema pallidum subspecies pertenue, the causative agent of yaws, Haemophilus ducreyi has emerged as a major cause of CU in yaws-endemic regions of the South Pacific islands and Africa. H. ducreyi is generally susceptible to macrolides, but CU strains persist after mass drug administration of azithromycin for yaws or trachoma. H. ducreyi also causes genital ulcers (GU) and was thought to be exclusively transmitted by microabrasions that occur during sex. In human volunteers, the GU strain 35000HP does not infect intact skin; wounds are required to initiate infection. These data led to several questions: Are CU strains a new variant of H. ducreyi or did they evolve from GU strains? Do CU strains contain additional genes that could allow them to infect intact skin? Are CU strains susceptible to azithromycin?Methodology/Principal FindingsTo address these questions, we performed whole-genome sequencing and antibiotic susceptibility testing of 5 CU strains obtained from Samoa and Vanuatu and 9 archived class I and class II GU strains. Except for single nucleotide polymorphisms, the CU strains were genetically almost identical to the class I strain 35000HP and had no additional genetic content. Phylogenetic analysis showed that class I and class II strains formed two separate clusters and CU strains evolved from class I strains. Class I strains diverged from class II strains ~1.95 million years ago (mya) and CU strains diverged from the class I strain 35000HP ~0.18 mya. CU and GU strains evolved under similar selection pressures. Like 35000HP, the CU strains were highly susceptible to antibiotics, including azithromycin.Conclusions/SignificanceThese data suggest that CU strains are derivatives of class I strains that were not recognized until recently. These findings require confirmation by analysis of CU strains from other regions.

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“…enterica , Typhimurium , Choleraesuis (C) Salmonellosis, foodborne diarrhea, BS β-Lactams bla OXA-30 , ampC , bla TEM-1 , bla TEM-67 [ 31 , 91 ] Quinolones (fluoroquinolones) gyrA (Ser83Leu), parC (Ser80Leu), acrAB-tolC [ 31 ] Aminoglycosides 2 copies aadA1 , 3 copies aadA3 , aac3 , aph , strA , strB , sat-1 [ 91 , 109 ] Shigella spp. (C) “Bacillary dysenteria” β-Lactams bla TEM-1 , bla OXA-1 [ 257 ] Fluoroquinolones mutated parC and gyrA [ 257 ] Aminoglycosides aadA1 , aadA2 , sat-1 [ 257 ] Neisseria gonorrhoeae (C) Gonorrhea β-Lactams (3rd gen. cephalosporins) mtrR (G45D, A39T), mtrCDE (del1327932), penB (G101K, A102D), penA (mosaic) [ 54 , 83 , 240 ] Tetracycline rpsJ (V57M), tetM including its promoter, penB [ 54 ] Coagulase-negative Staphylococci spp. (CoNS) (H, C) SSI, endocarditis, and BSI β-Lactams blaZ , mecC [ 25 , 173 , 184 ] Enterobacter aerogenes (H) SSI and BSI β-Lactams bla ...…”

Section: Introductionmentioning

confidence: 99%

Whole-genome sequencing targets drug-resistant bacterial infections

et al. 2015

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During the past two decades, the technological progress of whole-genome sequencing (WGS) had changed the fields of Environmental Microbiology and Biotechnology, and, currently, is changing the underlying principles, approaches, and fundamentals of Public Health, Epidemiology, Health Economics, and national productivity. Today’s WGS technologies are able to compete with conventional techniques in cost, speed, accuracy, and resolution for day-to-day control of infectious diseases and outbreaks in clinical laboratories and in long-term epidemiological investigations. WGS gives rise to an exciting future direction for personalized Genomic Epidemiology. One of the most vital and growing public health problems is the emerging and re-emerging of multidrug-resistant (MDR) bacterial infections in the communities and healthcare settings, reinforced by a decline in antimicrobial drug discovery. In recent years, retrospective analysis provided by WGS has had a great impact on the identification and tracking of MDR microorganisms in hospitals and communities. The obtained genomic data are also important for developing novel easy-to-use diagnostic assays for clinics, as well as for antibiotic and therapeutic development at both the personal and population levels. At present, this technology has been successfully applied as an addendum to the real-time diagnostic methods currently used in clinical laboratories. However, the significance of WGS for public health may increase if: (a) unified and user-friendly bioinformatics toolsets for easy data interpretation and management are established, and (b) standards for data validation and verification are developed. Herein, we review the current and future impact of this technology on diagnosis, prevention, treatment, and control of MDR infectious bacteria in clinics and on the global scale.

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Population structure ofNeisseria gonorrhoeaebased on whole genome data and its relationship with antibiotic resistance

Cited by 69 publications

References 53 publications

Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance

Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance

Haemophilus ducreyi Cutaneous Ulcer Strains Are Nearly Identical to Class I Genital Ulcer Strains

Whole-genome sequencing targets drug-resistant bacterial infections

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