Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa .

Autor:	Maia AR; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France., Cezard A; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France., Fouquenet D; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France., Vasseur V; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France., Briard B; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France., Sirard J-C; Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR8204 - CIIL - Center for Infection and Immunity of Lille, Lille, France., Si-Tahar M; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France., Hervé V; INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Tours, France.; Université de Tours, Faculté de Médecine, Tours, France.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 May 02; Vol. 68 (5), pp. e0136123. Date of Electronic Publication: 2024 Mar 25.
DOI:	10.1128/aac.01361-23
Abstrakt:	The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa (PA) is a significant concern for chronic respiratory disease exacerbations. Host-directed drugs, such as flagellin, an agonist of toll-like receptor 5 (TLR5), have emerged as a promising solution. In this study, we evaluated the prophylactic intranasal administration of flagellin against a multidrug-resistant strain of PA (PA MDR ) in mice and assessed the possible synergy with the antibiotic gentamicin (GNT). The results indicated that flagellin treatment before infection decreased bacterial load in the lungs, likely due to an increase in neutrophil recruitment, and reduced signs of inflammation, including proinflammatory cytokines. The combination of flagellin and GNT showed a synergistic effect, decreasing even more the bacterial load and increasing mice survival rates, in comparison to mice pre-treated only with flagellin. These findings suggest that preventive nasal administration of flagellin could restore the effect of GNT against MDR strains of PA, paving the way for the use of flagellin in vulnerable patients with chronic respiratory diseases. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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