Repurposing the Sphingosine-1-Phosphate Receptor Modulator Etrasimod as an Antibacterial Agent Against Gram-Positive...

Area of Science:

• Microbiology
• Pharmacology
• Drug Discovery

Background:

• Urgent need for novel antibiotics against multidrug-resistant bacteria.
• Drug repurposing accelerates antimicrobial research and development.
• Sphingosine-1-phosphate receptor (S1PR) modulators as a potential source of new antibacterial agents.

Purpose of the Study:

• Screen S1PR modulators for activity against Staphylococcus aureus.
• Evaluate etrasimod's antibacterial potential and mechanisms of action.
• Assess etrasimod's efficacy against various bacterial pathogens and its safety profile.

Main Methods:

• Screening of S1PR modulators against Staphylococcus aureus.
• Determination of Minimum Inhibitory Concentration (MIC) for various bacterial strains.
• Assessment of bactericidal activity, biofilm inhibition, quorum sensing inhibition, and in vitro mammalian cell toxicity.

Main Results:

• Etrasimod demonstrated potent inhibitory and bactericidal activity against Gram-positive bacteria, including methicillin-resistant S. aureus.
• Etrasimod showed activity against S. epidermidis and Enterococcus faecalis (MIC 5-10 μM).
• No activity against Gram-negative bacteria tested; however, it inhibited quorum sensing in Chromobacterium violaceum. Etrasimod exhibited synergistic effects with gentamicin and no in vitro toxicity to mammalian cells.

Conclusions:

• Etrasimod is a promising repurposed antibacterial compound effective against Gram-positive bacteria.
• Etrasimod's potential in combating antibiotic resistance and its utility in combination therapy warrant further investigation.
• The study highlights the value of drug repurposing for novel antimicrobial development.