Molecular Analysis of Pseudomonas aeruginosa Isolates with Mutant gyrA Gene and Development of a New Ciprofloxacin Derivative for Antimicrobial Therapy.

Publisher: Springer Country of Publication: Switzerland NLM ID: 9423533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0305 (Electronic) Linking ISSN: 10736085 NLM ISO Abbreviation: Mol Biotechnol Subsets: MEDLINE

Publication: [Cham] : Springer
Original Publication: Totowa, NJ : Humana Press, c1994-

Pseudomonas aeruginosa*/genetics ; Pseudomonas aeruginosa*/drug effects ; Ciprofloxacin*/pharmacology ; Ciprofloxacin*/chemistry ; DNA Gyrase*/genetics ; DNA Gyrase*/metabolism ; DNA Gyrase*/chemistry ; Molecular Docking Simulation* ; Mutation* ; Drug Resistance, Bacterial*/genetics ; Drug Resistance, Bacterial*/drug effects ; Anti-Bacterial Agents*/pharmacology ; Anti-Bacterial Agents*/chemistry ; Microbial Sensitivity Tests*; Humans ; Female ; Male ; Adult ; Middle Aged ; Pseudomonas Infections/drug therapy ; Pseudomonas Infections/microbiology

This study focuses on the prevalence of Pseudomonas aeruginosa in various medical specimens. In addition, the investigates of this research shows the genetic analysis of pathogen-resistant isolates and chemical modifications to ciprofloxacin. A total of 225 specimens from men and women aged 30 to 60 were carefully collected and examined, including samples from wound, burn, urine, sputum, and ear samples. The data were obtained from AL Muthanna hospitals. PCR-RFLP and gene expression analysis were used to identify resistant strains and explore the genetic basis of antibiotic resistance. A ciprofloxacin derivative was synthesized and confirmed through FT-IR, ¹ H-NMR, and mass spectroscopy techniques then it was tested as antibacterial agent. Also, molecular docking study was conducted to predict the mechanism of action for the synthesized derivative. The results demonstrated that wound samples had the highest positive rate (33.7%) of P. aeruginosa isolates. The PCR-RFLP testing correlated ciprofloxacin resistance with gyrA gene mutation. Gene expression analysis revealed significant changes in the gyrA gene expression in comparison to the reference rpsL gene subsequent to exposure to the synthesized derivative. Furthermore, the molecular docking investigation illustrated the strategic positioning of the ciprofloxacin derivative within the DNA-binding site of the gyrA enzyme. The examination of genetic expression patterns manifested diverse effects attributed to the CIP derivative on P. aeruginosa, thus portraying it as a viable candidate in the quest for the development of novel antimicrobial agents. Ciprofloxacin derivative may offer new antimicrobial therapeutic options for treating Pseudomonas aeruginosa infections in wound specimens, addressing resistance and gyrA gene mutations.
Competing Interests: Declarations. Conflict of interest: The authors claim no relevant conflicts of interest that affect the research. Ethical Approval: All procedures were conducted in strict adherence to the ethical standards of Al Muthanna University for the treatment of research subjects in Samawah, Iraq, following ethics- approval letter number 4513 in 4/11/2021. Informed Consent: Written informed consent has been received from all person’s individuals concerned in this study.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: Ciprofloxacin; Derivative ciprofloxacin; RFLP

5E8K9I0O4U (Ciprofloxacin)
EC 5.99.1.3 (DNA Gyrase)
0 (Anti-Bacterial Agents)

Date Created: 20240201 Date Completed: 20250108 Latest Revision: 20250108

20250114

10.1007/s12033-024-01076-y

38302682