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.