Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100
Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2024

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

Résumé

ABSTRACT 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.
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hal-04683300 , version 1 (02-09-2024)

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Ana Raquel Maia, Adeline Cezard, Delphine Fouquenet, Virginie Vasseur, Benoit Briard, et al.. Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 2024, 68 (5), pp.e01361-23. ⟨10.1128/aac.01361-23⟩. ⟨hal-04683300⟩
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