Preliminary investigations into developing all-D Omiganan for treating Mupirocin-resistant MRSA skin infections

Area of Science:

• Microbiology
• Dermatology
• Drug Development

Background:

• Staphylococcus aureus, particularly meticillin-resistant S. aureus (MRSA), is a major cause of human skin infections.
• Mupirocin resistance in MRSA is a growing clinical concern due to prolonged use of this topical antibiotic.
• The antimicrobial peptide Omiganan failed in clinical trials due to presumed proteolytic degradation by skin proteases.

Purpose of the Study:

• To investigate the hypothesis that endogenous human skin proteases degrade Omiganan.
• To evaluate the stability and anti-MRSA activity of Omiganan and its all-D enantiomer.
• To assess the potential of all-D Omiganan for topical antibacterial drug development against MRSA.

Main Methods:

• Protease stability assay using human skin proteases with Omiganan and its all-D enantiomer.
• In vitro anti-MRSA activity assays against clinical isolates.
• Determination of bactericidal/bacteriostatic activity.
• Time-kill assays to evaluate the rate of bacterial killing.

Main Results:

• The all-D enantiomer of Omiganan demonstrated stability against human skin proteases.
• The all-D Omiganan retained potent anti-MRSA activity against a panel of clinical isolates.
• Bactericidal and time-kill assays provided further data on the efficacy of all-D Omiganan.

Conclusions:

• Proteolytic degradation by skin proteases likely contributed to the previous failure of Omiganan.
• The all-D enantiomer of Omiganan overcomes protease instability and retains significant anti-MRSA activity.
• All-D Omiganan represents a promising candidate for the development of novel topical treatments against MRSA skin infections.