ArticleThe Journal of antimicrobial chemotherapy2023
High-level in vitro resistance to gentamicin acquired in a stepwise manner in Neisseria gonorrhoeae.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 9 citations in OpenAlex.
- Evidence for a Constrained Mutational Pathway to High-Level Spectinomycin Resistance inInternational journal of molecular sciences · 2026Article
- Gentamicin induction of the gonococcalmBio · 2025Article
- Common Patterns and Unique Threats in Antimicrobial Resistance as Demonstrated by Global Gonococcal Surveillance.Emerging infectious diseases · 2024Article
- In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Rolling the evolutionary dice:Microbiology spectrum · 2024Article
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
objectivesGentamicin is used in several alternative treatments for gonorrhoea. Verified clinical Neisseria gonorrhoeae isolates with gentamicin resistance are mainly lacking and understanding the mechanisms for gonococcal gentamicin resistance is imperative. We selected gentamicin resistance in gonococci in vitro, identified the novel gentamicin-resistance mutations, and examined the biofitness of a high-level gentamicin-resistant mutant.
methodsLow- and high-level gentamicin resistance was selected in WHO X (gentamicin MIC = 4 mg/L) on gentamicin-gradient agar plates. Selected mutants were whole-genome sequenced. Potential gentamicin-resistance fusA mutations were transformed into WT strains to verify their impact on gentamicin MICs. The biofitness of high-level gentamicin-resistant mutants was examined using a competitive assay in a hollow-fibre infection model.
resultsWHO X mutants with gentamicin MICs of up to 128 mg/L were selected. Primarily selected fusA mutations were further investigated, and fusAR635L and fusAM520I + R635L were particularly interesting. Different mutations in fusA and ubiM were found in low-level gentamicin-resistant mutants, while fusAM520I was associated with high-level gentamicin resistance. Protein structure predictions showed that fusAM520I is located in domain IV of the elongation factor-G (EF-G). The high-level gentamicin-resistant WHO X mutant was outcompeted by the gentamicin-susceptible WHO X parental strain, suggesting lower biofitness.
conclusionsWe describe the first high-level gentamicin-resistant gonococcal isolate (MIC = 128 mg/L), which was selected in vitro through experimental evolution. The most substantial increases of the gentamicin MICs were caused by mutations in fusA (G1560A and G1904T encoding EF-G M520I and R635L, respectively) and ubiM (D186N). The high-level gentamicin-resistant N. gonorrhoeae mutant showed impaired biofitness.
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