Novel Cyclic Lipopeptides Fusaricidin Analogs for Treating Wound Infections

Frontiers in Microbiology

Predrag Cudic¹  Brandon Williams¹  Alexander Higa²  Stephen C. Davis²  Cheyanne R. Head²  Joel Gil²  Michael Solis²  Irena Pastar²  Jose Valdez²  Colin Simms²  Heather Michaels³  Richard A. Houghten³  Brian Lenhart³  Shruti Padhee³ 

[1] Department of Chemistry and Biochemistry Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL, United States;Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miller School of Medicine, University of Miami, Coral Gables, FL, United States;Torrey Pines Institute for Molecular Studies, San Diego, CA, United States;

关键词: Pseudomonas aeruginosa;    methicillin-resistant Staphylococcus aureus;    wound healing;    porcine (pig) model;    wound;    biofilm model;   

DOI  :  10.3389/fmicb.2021.708904

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown