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

Abstract

Staphylococcus aureus is the primary pathogen responsible for the majority of human skin infections, and meticillin-resistant S. aureus (MRSA) currently presents a major clinical concern. The overuse of Mupirocin, the first-line topical antibacterial drug over 30 years, has led to the emergence of Mupirocin-resistant MRSA, creating a clinical concern. The antimicrobial peptide Omiganan was touted to be a promising antibacterial drug candidate due to its rapid membrane-disrupting bactericidal mode of action, entering clinical trials in 2005 as a topical gel to prevent catheter site infections. However, drug development ceased in 2009 due to a lack of efficacy. We postulate this to be due to proteolytic degradation caused by endogenous human skin proteases. Herein, we tested our hypothesis using Omiganan and its all-D enantiomer in a human skin protease stability assay, followed by anti-MRSA activity assay against of a panel of clinical MRSA isolates, a bactericidal/static determination and a time-kill assay to gauge all-D Omiganan's potential for further topical antibacterial drug development.

Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance

“…Interestingly, little mechanistic data has been reported to elucidate its immunomodulatory influence on host cells. In vitro, omiganan has broad spectrum antimicrobial and antifungal activity against numerous resistant species including S. aureus and Candida albicans, respectively; however, proteases endogenous to the skin can cause deactivation of the peptide in situ (Ng et al, 2017). In contrast, the D-enantiomer of omiganan is metabolically stable toward skin proteases and is comparable to the L-enantiomer in terms of antibacterial and antifungal potency.…”

Synthetic Naphthofuranquinone Derivatives Are Effective in Eliminating Drug-Resistant Candida albicans in Hyphal, Biofilm, and Intracellular Forms: An Application for Skin-Infection Treatment

“…Our results demonstrated that naphthofuranquinones were fungicidal. An ideal biocidal agent should kill the microbes quickly to avoid the opportunity for resistance development (Ng et al, 2017). Our timekilling curve showed a rapid fungicidal effect with the use of TCH-1140 and TCH-1142.…”

Staphylococcus aureus: an underestimated factor in the pathogenesis of atopic dermatitis?

“…The study of several AMPs introduced in catheter infections caused by biofilm-forming S. aureus has revealed high effectiveness of the treatment, especially in case of D-Bac8c2,5Leu [92]. Additionally, some promising data have come from the research over all-D omiganan, which has shown bactericidal activity towards S. aureus and satisfactory half-life in vivo [93].…”