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

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Author(s): Adèle Sakr, Frédéric Laurent, Jean Michel Brunel, Tania Nawfal Dagher, Olivier Blin, Jean Marc Rolain *.

Journal Name: Anti-Infective Agents

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Abstract:

Background and Objective: 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. The objective of our study was to evaluate the antibacterial activity of polyaminosteroid derivatives against S. aureus strains with different levels of mupirocin-resistance.

Methods and Results: Using the broth microdilution method, we evaluated the minimum inhibitory concentration (MIC) of these molecules against S. aureus clinical strains including mupirocin-resistant strains. We found that squalamine and one of its analogues, named BSQ-1, are active against mupirocin-susceptible and -resistant clinical isolates with MIC values of 3.125 µg/mL. Additionally, long-term and repeated exposure of a susceptible 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.

Keywords: Polyaminosteroid derivatives , squalamine analogues, Staphylococcus aureus, mupirocin-resistant S. aureus, mupirocin, nasal decolonization

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(E-pub Ahead of Print)
DOI: 10.2174/2211352517666190723092347