Novel Cyclic Lipopeptides Fusaricidin Analogs for Treating Wound Infections

Abstract

Both acute and chronic cutaneous wounds are often difficult to treat due to the high-risk for bacterial contamination. Once hospitalized, open wounds are at a high-risk for developing hospital-associated infections caused by multi drug-resistant bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. Treating these infections is challenging, not only because of antibiotic resistance, but also due to the production of biofilms. New treatment strategies are needed that will help in both stimulating the wound healing process, as well as preventing and eliminating bacterial wound infections. Fusaricidins are naturally occurring cyclic lipopeptides with antimicrobial properties that have shown to be effective against a variety of fungi and Gram-positive bacteria, with low toxicity. Continuing with our efforts toward the identification of novel cyclic lipopeptides Fusaricidin analogs, herein we report the synthesis and evaluation of the antimicrobial activity for two novel cyclic lipopeptides (CLP), CLP 2605-4 and CLP 2612-8.1 against methicillin resistant S. aureus and P. aeruginosa, respectively, in in vivo porcine full thickness wound model. Both CLPs were able to reduce bacterial counts by approximately 3 log CFU/g by the last assessment day. Peptide 2612-8.1 slightly enhanced the wound healing, however, wounds treated with peptide 2605-4, have shown higher levels of inflammation and impaired wound healing process. This study highlights the importance of identifying new antimicrobials that can combat bacterial infection while not impeding tissue repair.

Effect of Moringa oleifera Leaf Extract on Excision Wound Infections in Rats: Antioxidant, Antimicrobial, and Gene Expression Analysis

“…Delayed wound healing with bacterial infections results in high treatment costs and increased morbidity [ 33 ]. Prevention of bacterial infections is an important priority in cutaneous wound management [ 34 ]. In this study, MRSA or P. aeruginosa was selected to represent two wide groups of Gram-positive and Gram-negative bacteria to establish the wide spectrum activity of the extract.…”

Biocontrol potential of lipopeptides produced by Paenibacillus polymyxa AF01 against Neoscytalidium dimidiatum in pitaya

“…These compounds comprised a guanidinylated β-hydroxy fatty acid and a cyclic hexapeptide. Paenibacillus stains produced various types of fusaricidins ( Gil et al, 2021 ), where enormous diversity exists even within those found in the same bacterial. MALDI-TOF MS is a practical technique for detecting secondary metabolites without additional purification, allowing the identification of active compounds in crude extracts via mass spectrometry.…”

Staphylococcus aureus and biofilms: transmission, threats, and promising strategies in animal husbandry

“…In addition, this peptide binds to bacterial genomic DNA to suppress the expression of the Panton-Valentine leukocidin and nuclease genes, which play major roles in S. aureus virulence. Gil et al [ 88 ] designed novel cyclic lipopeptides based on Fusarium analogues. The novel cyclic lipopeptide exhibited antimicrobial activity against MRSA in an in vivo porcine full-thickness wound model, resulting in a reduction in the bacterial count of approximately 3 log CFU/g and a slight increase in wound healing.…”