Enhancing colistin efficacy against Salmonella infections with a quinazoline-based dual therapeutic strategy.

Autor: Lobertti CA; Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad Nacional de Rosario, Predio CCT-CONICET Rosario, S2000, Santa Fe, Rosario, Argentina., Gizzi FO; Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad Nacional de Rosario, Predio CCT-CONICET Rosario, S2000, Santa Fe, Rosario, Argentina., Magni C; Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad Nacional de Rosario, Predio CCT-CONICET Rosario, S2000, Santa Fe, Rosario, Argentina., Rial A; Departamento de Desarrollo Biotecnológico, Facultad de Medicina, Instituto de Higiene, Universidad de La República, Avda. Alfredo Navarro 3051, 11600, Montevideo, Uruguay., Chabalgoity JA; Departamento de Desarrollo Biotecnológico, Facultad de Medicina, Instituto de Higiene, Universidad de La República, Avda. Alfredo Navarro 3051, 11600, Montevideo, Uruguay., Yim L; Departamento de Desarrollo Biotecnológico, Facultad de Medicina, Instituto de Higiene, Universidad de La República, Avda. Alfredo Navarro 3051, 11600, Montevideo, Uruguay., Blancato VS; Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad Nacional de Rosario, Predio CCT-CONICET Rosario, S2000, Santa Fe, Rosario, Argentina., Asquith CRM; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211, Kuopio, Finland., García Véscovi E; Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Tecnológicas, Universidad Nacional de Rosario, Predio CCT-CONICET Rosario, S2000, Santa Fe, Rosario, Argentina. garciavescovi@ibr-conicet.gov.ar.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Mar 01; Vol. 14 (1), pp. 5148. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1038/s41598-024-55793-0
Abstrakt: Colistin remains one of the last-resort therapies for combating infections caused by multidrug-resistant (MDR) Enterobacterales, despite its adverse nephro- and neuro-toxic effects. This study elucidates the mechanism of action of a non-antibiotic 4-anilinoquinazoline-based compound that synergistically enhances the effectiveness of colistin against Salmonella enterica. The quinazoline sensitizes Salmonella by deactivating intrinsic, mutational, and transferable resistance mechanisms that enable Salmonella to counteract the antibiotic impact colistin, together with an induced disruption to the electrochemical balance of the bacterial membrane. The attenuation of colistin resistance via the combined treatment approach also proves efficacious against E. coli, Klebsiella, and Acinetobacter strains. The dual therapy reduces the mortality of Galleria mellonella larvae undergoing a systemic Salmonella infection when compared to individual drug treatments. Overall, our findings unveil the potential of the quinazoline-colistin combined therapy as an innovative strategy against MDR bacteria.
(© 2024. The Author(s).)
Databáze: MEDLINE
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