WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC &gt;2 mg/L)<i>Neisseria gonorrhoeae</i>isolates in Europe from 2009 to 2014

Jacobsson, Susanne; Golparian, Daniel; Cole, Michelle; Spiteri, Gianfranco; Martín, Irene; Bergheim, Thea; Borrego, Maria José; Crowley, Brendan; Crucitti, Tania; Dam, Alje P. van; Hoffmann, Steen; Jeverica, Samo; Kohl, Peter K.; Młynarczyk-Bonikowska, Beata; Pakarna, Gatis; Stary, Angelika; Stefanelli, Paola; Pavlik, Peter; Tzelepi, E.; Abad, Raquel; Harris, Simon R.; Unemo, Magnus

doi:10.1093/jac/dkw279

Cited by 83 publications

(75 citation statements)

References 37 publications

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“…Chromosomal mutations mediating low‐level resistance to beta‐lactams and tetracycline are common in N. gonorrhoeae isolates, and they are widespread across the phylogeny . While azithromycin resistance is less common than resistance to previously used drugs, resistance or reduced susceptibility has arisen across a large number of genomic backgrounds . In contrast, reduced susceptibility to ESCs (ESC‐RS) is primarily clonal, and the majority of ESC‐RS isolates belong to only a few major lineages .…”

Section: From Pathogen To Superbug: Treatment and Resistancementioning

confidence: 99%

“…22 While azithromycin resistance is less common than resistance to previously used drugs, resistance or reduced susceptibility has arisen across a large number of genomic backgrounds. 22,78,79 In contrast, reduced susceptibility to ESCs (ESC-RS) is primarily clonal, and the majority of ESC-RS isolates belong to only a few major lineages. 22,50 In isolates from the United States, azithromycin reduced susceptibility (AZI-RS) is estimated to have been acquired 75 times, and reversion to susceptibility is also relatively frequent (42 times).…”

Section: Acquisition Of Antibiotic Resistancementioning

confidence: 99%

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Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

Mortimer

Grad

2018

Annals of the New York Academy of Sciences

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Infections with Neisseria gonorrhoeae, a sexually transmitted pathogen that causes urethritis, cervicitis, and more severe complications, are increasing. Gonorrhea is typically treated with antibiotics; however, N. gonorrhoeae has rapidly acquired resistance to many antibiotic classes, and lineages with reduced susceptibility to the currently recommended therapies are emerging worldwide. In this review, we discuss the contributions of whole genome sequencing (WGS) to our understanding of resistant N. gonorrhoeae. Genomics has illuminated the evolutionary origins and population structure of N. gonorrhoeae and the magnitude of horizontal gene transfer within and between Neisseria species. WGS can be used to predict the susceptibility of N. gonorrhoeae based on known resistance determinants, track the spread of these determinants throughout the N. gonorrhoeae population, and identify novel loci contributing to resistance. WGS has also allowed more detailed epidemiological analysis of transmission of N. gonorrhoeae between individuals and populations than previously used typing methods. Ongoing N. gonorrhoeae genomics will complement other laboratory techniques to understand the biology and evolution of the pathogen, improve diagnostics and treatment in the clinic, and inform public health policies to limit the impact of antibiotic resistance.

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Section: From Pathogen To Superbug: Treatment and Resistancementioning

confidence: 99%

Section: Acquisition Of Antibiotic Resistancementioning

confidence: 99%

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

Mortimer

Grad

2018

Annals of the New York Academy of Sciences

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“…Effective STI control will require the political will to prioritise and invest in new 150 rapid molecular methods for predicting AMR (for AMR surveillance but ideally also to inform individualized treatment), [190][191][192] rapid point of care tests for diagnosis of gonorrhoea (ideally with combined prediction of AMR); 190,191 ideal phylogenomics of gonococci and their AMR (also in non-cultured samples); 159,457,[459][460][461][462][463][464] and appropriate models for pharmacokinetics/ pharmacodynamics (urogenital and extragenital sites) and prediction of AMR induction/selection, evolution and biological fitness. -Data are for principal diagnosis, recorded using the ICD-9-CM from 1993-94 to 1997-98, and recording using the ICD-10-AM (Australian modification) from 1998-99.…”

mentioning

confidence: 99%

Sexually transmitted infections: challenges ahead

Unemo

Bradshaw

Hocking

et al. 2017

The Lancet Infectious Diseases

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565

469

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“…DNA sequence analysis revealed that all 14 isolates harbored the mosaic-mtr and the A2059G mutation in all four copies of their 23S rRNA gene. While investigators from many countries have reported on the A2059G mutation or the mosaic-mtr, none described these two haplotypes together (5,10,(12)(13)(14)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The 14 isolates in this study are the first known isolates to have possessed both the A2059G mutation and the mosaic-mtr.…”

Section: Resultsmentioning

confidence: 79%

Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-Attenuating Mutations

Pham

Sharpe

Schlanger

et al. 2019

Antimicrob Agents Chemother

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The nimbleness of Neisseria gonorrhoeae to evade the effect of antibiotics has perpetuated the fight against antibiotic-resistant gonorrhea for more than 80 years. The ability to develop resistance to antibiotics is attributable to its indiscriminate nature in accepting and integrating exogenous DNA into its genome. Here, we provide data demonstrating a novel combination of the 23S rRNA A2059G mutation with a mosaic-multiple transferable resistance (mosaic-mtr) locus haplotype in 14 N. gonorrhoeae isolates with high-level azithromycin MICs (Ն256 g/ ml), a combination that may confer more fitness than in previously identified isolates with high-level azithromycin resistance. To our knowledge, this is the first description of N. gonorrhoeae strains harboring this novel combination of resistance determinants. These strains were isolated at two independent jurisdictions participating in the Gonococcal Isolate Surveillance Project (GISP) and in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) project. The data suggest that the genome of N. gonorrhoeae continues to shuffle its genetic material. These findings further illuminate the genomic plasticity of N. gonorrhoeae, which allows this pathogen to develop mutations to escape the inhibitory effects of antibiotics.

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WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L)Neisseria gonorrhoeaeisolates in Europe from 2009 to 2014

Cited by 83 publications

References 37 publications

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

Sexually transmitted infections: challenges ahead

Emergence of Neisseria gonorrhoeae Strains Harboring a Novel Combination of Azithromycin-Attenuating Mutations

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