Exploration of the novel fluoroquinolones with high inhibitory effect against quinolone-resistant DNA gyrase of SalmonellaTyphimurium
Issued Date
2023-12-01
Resource Type
eISSN
21650497
Scopus ID
2-s2.0-85179587713
Pubmed ID
37795999
Journal Title
Microbiology Spectrum
Volume
11
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Microbiology Spectrum Vol.11 No.6 (2023)
Suggested Citation
Toyting J., Miura N., Utrarachkij F., Tanomsridachchai W., Belotindos L.P., Suwanthada P., Kapalamula T.F., Kongsoi S., Koide K., Kim H., Thapa J., Nakajima C., Suzuki Y. Exploration of the novel fluoroquinolones with high inhibitory effect against quinolone-resistant DNA gyrase of SalmonellaTyphimurium. Microbiology Spectrum Vol.11 No.6 (2023). doi:10.1128/spectrum.01330-23 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/95642
Title
Exploration of the novel fluoroquinolones with high inhibitory effect against quinolone-resistant DNA gyrase of SalmonellaTyphimurium
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Corresponding Author(s)
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Abstract
Quinolone-resistant nontyphoidal Salmonella, one of the prominent pathogens causing acute gastroenteritis, has become a public health concern globally. The World Health Organization has ranked fluoroquinolone-resistant Salmonella as a high-priority pathogen for researching and developing new antibiotics. WQ-3034 and WQ-3154 are relatively new synthetic fluoroquinolones with distinctive structures. WQ-3034 has 6-amino-3,5-difluoropyridine-2-yl at R1, 3-hydroxyazetidinyl at R7, and the addition of chlorine atom at R8. WQ-3154 has a similar basic pharmacophore to WQ-3034 except for the modification at R8 with a methyl group. In this study, the inhibitory effect and DNA cleavage effect against wild-type (WT) and mutant Salmonella Typhimurium DNA gyrases of WQ-3034 and WQ-3154 were examined along with WQ-3810 and ciprofloxacin by measuring the drug concentration that inhibits half of the enzyme activity (IC50) and the drug concentration that induces 25% of maximum DNA cleavage (CC25). The minimum inhibitory concentration (MIC) of the compounds was assessed against Salmonella Typhimurium and Salmonella Enteritidis. Among four compounds, WQ-3034 demonstrated the highest inhibitory effect against both WT and mutant Salmonella Typhimurium DNA gyrases with amino acid substitution at codon 83 and/or 87, while ciprofloxacin showed the lowest inhibitory effect. Remarkably, WQ-3034 and WQ-3154 exhibited a significantly higher inhibitory effect than ciprofloxacin against Salmonella Typhimurium DNA gyrase with double amino acid substitution, Ser83Phe-Asp87Asn. Similarly, CC25 of WQ-3034 against mutant Salmonella Typhimurium DNA gyrase was lower than ciprofloxacin. Notably, MICs of WQ-3034 and WQ-3154 were higher than ciprofloxacin. In conclusion, this study revealed that WQ-3034 and WQ-3154 could potentially be effective therapeutic agents against quinolone-resistant nontyphoidal Salmonella. IMPORTANCE Quinolone-resistant nontyphoidal Salmonella is a pressing public health concern, demanding the exploration of novel treatments. In this study, we focused on two innovative synthetic fluoroquinolones, WQ-3034 and WQ-3154. Our findings revealed that these new compounds demonstrate potent inhibitory effects, even against mutant strains that cause resistance to existing quinolones. Hence, WQ-3034 and WQ-3154 could potentially be effective therapeutic agents against quinolone-resistant Salmonella Typhimurium. Furthermore, the data obtained in this study will be baseline information for antimicrobial drug development.