ArticleThe Lancet. Microbe2022
Loci for prediction of penicillin and tetracycline susceptibility in Neisseria gonorrhoeae: a genome-wide association study.
Article in The Lancet. Microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
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- Revisiting the potential impact of doxycycline post-exposure prophylaxis on the selection of doxycycline resistance in Neisseria commensals.Scientific reports · 2025Article
- Antimicrobial Resistance in Curable Sexually Transmitted Infections.Current HIV/AIDS reports · 2025Review
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- The Impact of Rapid Drug Susceptibility Tests on Gonorrhea Burden and the Life Span of Antibiotic Treatments: A Modeling Study Among Men Who Have Sex With Men in the United States.American journal of epidemiology · 2024Article
- Evolution and exchange of plasmids in pathogenicmSphere · 2023Article
- Genome-Wide Association Studies (GWAS) Approaches for the Detection of Genetic Variants Associated with Antibiotic Resistance: A Systematic Review.Microorganisms · 2023Review
- A Genomic Perspective on the Near-term Impact of Doxycycline Post-exposure Prophylaxis on Neisseria gonorrhoeae Antimicrobial Resistance.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Neisseria gonorrhoeae diagnostic escape from a gyrA-based test for ciprofloxacin susceptibility and the effect on zoliflodacin resistance: a bacterial genetics and experimental evolution study.The Lancet. Microbe · 2023Article
- Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests.Annals of the New York Academy of Sciences · 2023Review
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- WGS-Based Lineage and Antimicrobial Resistance Pattern ofAntibiotics (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundNeisseria gonorrhoeae poses an urgent public health threat because of increasing antimicrobial resistance; however, much of the circulating population remains susceptible to historical treatment regimens. Point-of-care diagnostics that report susceptibility could allow for reintroduction of these regimens, but development of such diagnostics has been restricted to ciprofloxacin, for which susceptibility can be predicted from a single locus. We aimed to define genetic variants associated with susceptibility to penicillin and tetracycline.
methodsWe collected publicly available global whole-genome sequencing data (n=12 045) from clinical N gonorrhoeae isolates, with phenotypic resistance data for penicillin (n=6935), and tetracycline (n=5727). Using conditional genome-wide association studies, we defined genetic variants associated with susceptibility to penicillin and tetracycline. We excluded isolates that could not be classified as either susceptible or resistant. To validate our results, we assembled 1479 genomes from the US Centers for Disease Control and Prevention (CDC)'s Gonococcal Isolate Surveillance Project, for which urethral specimens are collected at sentinel surveillance sites across the USA. We evaluated the sensitivity and specificity of susceptibility-associated alleles using Clinical & Laboratory Standards Institute breakpoints for susceptibility and non-resistance in both the global and validation datasets.
findingsIn our conditional penicillin genome-wide association study, the presence of a genetic variant defined by a non-mosaic penA allele without an insertion at codon 345 was associated with penicillin susceptibility and had the highest negative effect size (β) of significant variants (p=5·0x10
interpretationAs few as two genetic loci can predict susceptibility to penicillin and tetracycline in N gonorrhoeae with high specificity. Molecular point-of-care diagnostics targeting these loci have the potential to increase available treatments for gonorrhoea.
fundingNational Institute of Allergy and Infectious Diseases, the National Science Foundation, and the Smith Family Foundation.
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