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

LOBERTTI, CARLOS A.; GIZZI, FERNÁN O.; MAGNI, CHRISTIAN; RIAL, ANALÍA; CHABALGOITY, JOSÉ A.; YIM, LUCÍA; BLANCATO, VÍCTOR S.; ASQUITH, CHRISTOPHER R. M.; GARCÍA VÉSCOVI, ELEONORA

Scientific Reports

Springer Nature

Lugar: Berlin; Año: 2024 vol. 14

Colistin remains one of the last-resort therapies for combating infections caused by multidrug resistant (MDR) Enterobacterales, despite its adverse nephro- and neuro-toxic efects. This study elucidates the mechanism of action of a non-antibiotic 4-anilinoquinazoline-based compound that synergistically enhances the efectiveness 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 efcacious 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 fndings unveil the potential of the quinazoline-colistin combined therapy as an innovative strategy against MDR bacteria