Polyaminosteroid Analogues as Potent Antibacterial Agents Against Mupirocin- Resistant Staphylococcus aureus Strains

Author:

Sakr Adèle1ORCID,Laurent Fréderic2ORCID,Brunel Jean-Michel3ORCID,Dagher Tania Nawfal4ORCID,Blin Olivier5ORCID,Rolain Jean-Marc4ORCID

Affiliation:

1. Biosqual SAS, Marseille, France

2. Centre International de Recherche en Infectiologie, INSERM U1111, CNRS UMR5308, Universite de Lyon 1, ENS de Lyon, Team “Pathogenesis of Staphylococcal infections”, Lyon, France

3. Aix-Marseille Universite, UMR-MD1, U-1261 INSERM, Faculte de Pharmacie, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France

4. Aix Marseille Universite, IRD, APHM, MEPHI, IHU Mediterranée Infection, Faculte de Medecine et de Pharmacie, 19-21 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France

5. Service de Pharmacologie Clinique et Pharmacovigilance, AP-HM, Pharmacologie Integrée et Interface Clinique et Industriel, Institut des Neurosciences Timone – UMR AMU-INSERM 1106, Aix Marseille Universite, 13385 Marseille, Marseille, France

Abstract

Background: Nasal carriage of Staphylococcus aureus (S. aureus) constitutes an important risk factor for subsequent infections in some types of patient populations. Decolonization of carriers using intranasal mupirocin is widely used as a preventive measure. However, resistance to this agent has been rising and causing failure in the decolonization, highlighting the need for new alternatives. Objective: The objective of our study was to evaluate the antibacterial activity of polyaminosteroid analogues (squalamine and BSQ-1) against S. aureus strains with different levels of mupirocin-resistance. Methods: Using the broth microdilution method, we evaluated the minimum inhibitory concentration (MIC) of these molecules against S. aureus clinical strains including mupirocin-resistant strains. The emergence of resistance was evaluated by long-term and repeated exposure of a susceptible S. aureus strain to subinhibitory concentrations of squalamine, BSQ-1 or mupirocin. Results: We found that squalamine and BSQ-1 are active against mupirocin-susceptible and -resistant clinical isolates with MIC values of 3.125 μg/mL. Additionally, repeated exposure of a S. aureus strain to squalamine and BSQ-1 did not lead to the emergence of resistant bacteria, contrarily to mupirocin. Conclusion: Our study suggests that these molecules constitute promising new alternatives to mupirocin for nasal decolonization and prevention of endogenous infections.

Funder

Agence Nationale de la Recherche

Publisher

Bentham Science Publishers Ltd.

Subject

Infectious Diseases,Pharmacology

Reference39 articles.

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