Intracellular activity and in vivo efficacy in a mouse model of septic arthritis of the novel pseudopeptide Pep16 against Staphylococcus aureus clinical isolates - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue JAC-Antimicrobial Resistance Année : 2024

Intracellular activity and in vivo efficacy in a mouse model of septic arthritis of the novel pseudopeptide Pep16 against Staphylococcus aureus clinical isolates

Résumé

Objectives - Assessing the therapeutic potential of a novel antimicrobial pseudopeptide, Pep16, both and for the treatment of septic arthritis caused by . Methods - Seven clinical isolates of (two MRSA and five MSSA) were studied. MICs of Pep16 and comparators (vancomycin, teicoplanin, daptomycin and levofloxacin) were determined through the broth microdilution method. The intracellular activity of Pep16 and levofloxacin was assessed in two models of infection using non-professional (osteoblasts MG-63) or professional (macrophages THP-1) phagocytic cells. A mouse model of septic arthritis was used to evaluate the efficacy of Pep16 and vancomycin. A preliminary pharmacokinetic (PK) analysis was performed by measuring plasma concentrations using LC-MS/MS following a single subcutaneous injection of Pep16 (10 mg/kg). Results - MICs of Pep16 were consistently at 8 mg/L for all clinical isolates of (2- to 32-fold higher to those of comparators) while MBC/MIC ratios confirmed its bactericidal activity. Both Pep16 and levofloxacin (when used at 2 × MIC) significantly reduced the bacterial load of all tested isolates (two MSSA and two MRSA) within both osteoblasts and macrophages. In MSSA-infected mice, Pep16 demonstrated a significant (∼10-fold) reduction on bacterial loads in knee joints. PK analysis following a single subcutaneous administration of Pep16 revealed a gradual increase in plasma concentrations, reaching a peak of 5.6 mg/L at 12 h. Conclusions - Pep16 is a promising option for the treatment of septic arthritis due to , particularly owing to its robust intracellular activity.

Dates et versions

hal-04513158 , version 1 (20-03-2024)

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Jean-Baptiste Mascary, Valérie Bordeau, Irène Nicolas, Marie-Clémence Verdier, Pierre Rocheteau, et al.. Intracellular activity and in vivo efficacy in a mouse model of septic arthritis of the novel pseudopeptide Pep16 against Staphylococcus aureus clinical isolates. JAC-Antimicrobial Resistance, 2024, Jac-Antimicrobial Resistance, 6 (1), pp.dlae025. ⟨10.1093/jacamr/dlae025⟩. ⟨hal-04513158⟩
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