A Single Amino Acid Substitution in Elongation Factor G Can Confer Low-Level Gentamicin Resistance in
            <i>Neisseria gonorrhoeae</i>

Holley, Concerta L.; Dhulipala, Vijaya; Balthazar, Jacqueline T.; Van, Adriana Le; Begum, Afrin A.; Chen, Shao-Chun; Read, Timothy D.; Matoga, Mitch; Hoffman, Irving; Golparian, Daniel; Unemo, Magnus; Jerse, Ann E.; Shafer, William M.

doi:10.1128/aac.00251-22

Cited by 5 publications

(2 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the three antibiotics having different targets in mind, this might suggest these antibiotics share an unidenti ed common target or fusA regulates unknown metabolic processes. It has been found that the mutation of this gene can confer low level gentamicin resistance to Neisseria gonorrhoeae 27 . These effects and the corresponding molecular mechanisms need to be further veri ed and explored.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Staphylococcus aureus antibiotics resistance revealed by adaptive laboratory evolution

Ma,

Xu,

Luo

et al. 2024

Preprint

View full text Add to dashboard Cite

Infection caused by drug-resistant Staphylococcus aureus is a rapidly developing public health and veterinary concern. Lack of a comprehensive understanding of the mechanisms underlying the emergence of drug-resistant strains, it makes S. aureus one of the most intractable pathogenic bacteria. To identify mutations that confer resistance to anti-S.aureus drugs, we established a laboratory-based adaptive evolution system and performed 10 rounds of evolution experiments against 15 clinically used antibiotics. We discovered a panel of known and novel resistance-associated sites after performing whole-genome sequencing. Furthermore, we found that the resistance evolved at distinct rates. For example, streptomycin, rifampicin, fusidic acid and novobiocin all developed significant resistance quickly in the second round of evolution. Intriguingly, the cross-resistance experiment reveals that nearly all drug-resistant strains have varying degrees of increased sensitivity to fusidic acid, pointing to a novel approach to battle AMR. In addition, the in silico docking analysis shows that the evolved mutants affect the interaction of rifampcin-rpoB, as well as the novobiocin-gyrB. Moreover, for the genes we got in the laboratory evolution, mutant genes of clinical isolates of human had significant differences from the environmental isolates and animal isolates. In conclusion, we believe that the strategy and dataset in this research will be helpful for battling AMR issue of S.aureus, and adaptable to other pathogenic microbes.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms of Staphylococcus aureus antibiotics resistance revealed by adaptive laboratory evolution

Ma,

Xu,

Luo

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Very few isolates originally reported as resistant with gentamicin MICs of > 32 μg/mL were communicated to not be reproducible in repeat susceptibility testing when using E tests instead of agar dilution [ 26 – 28 ], an observation supported by our own findings as well. In vitro selection pressure and passaging experiments have recently identified mutations in the fusA gene, coding for the ribosomal elongation factor G, as possible gentamicin resistance determinants in N. gonorrhoeae , but the clinical relevance of such laboratory-induced mutations has yet to be elucidated [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides

Gross,

Herren,

Gysin

et al. 2024

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

Purpose Single doses of gentamicin have demonstrated clinical efficacy in the treatment of urogenital gonorrhea, but lower cure rates for oropharyngeal and anorectal gonorrhea. Formulations selectively enriched in specific gentamicin C congeners have been proposed as a less toxic alternative to gentamicin, potentially permitting higher dosing to result in increased plasma exposures at the extragenital sites of infection. The purpose of the present study was to compare the antibacterial activity of individual gentamicin C congeners against Neisseria gonorrhoeae to that of other aminoglycoside antibiotics. Methods Antimicrobial susceptibility of three N. gonorrhoeae reference strains and 152 clinical isolates was assessed using standard disk diffusion, agar dilution, and epsilometer tests. Results Gentamicin C1, C2, C1a, and C2a demonstrated similar activity against N. gonorrhoeae. Interestingly, susceptibility to the 1-N-ethylated aminoglycosides etimicin and netilmicin was significantly higher than the susceptibility to their parent compounds gentamicin C1a and sisomicin, and to any other of the 25 aminoglycosides assessed in this study. Propylamycin, a 4’-propylated paromomycin analogue, was significantly more active against N. gonorrhoeae than its parent compound, too. Conclusion Selectively enriched gentamicin formulations hold promise for a less toxic but equally efficacious alternative to gentamicin. Our study warrants additional consideration of the clinically established netilmicin and etimicin for treatment of genital and perhaps extragenital gonorrhea. Additional studies are required to elucidate the mechanism behind the advantage of alkylated aminoglycosides.

show abstract

Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study

Golparian,

Cole,

Sánchez-Busó

et al. 2024

The Lancet Microbe

View full text Add to dashboard Cite

A Single Amino Acid Substitution in Elongation Factor G Can Confer Low-Level Gentamicin Resistance in Neisseria gonorrhoeae

Cited by 5 publications

References 55 publications

Mechanisms of Staphylococcus aureus antibiotics resistance revealed by adaptive laboratory evolution

Mechanisms of Staphylococcus aureus antibiotics resistance revealed by adaptive laboratory evolution

In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides

Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study

Contact Info

Product

Resources

About