Evaluation of the Antimicrobial Peptide, RP557, for the Broad-Spectrum Treatment of Wound Pathogens and Biofilm

Abstract

The relentless growth of multidrug resistance and generation of recalcitrant biofilm are major obstacles in treating wounds, particularly in austere military environments where broad-spectrum pathogen coverage is needed. Designed antimicrobial peptides (dAMPs) are constructed analogs of naturally occurring AMPs that provide the first line of defense in many organisms. RP557 is a dAMP resulting from iterative rational chemical structural analoging with endogenous AMPs, human cathelicidin LL-37 and Tachyplesin 1 and the synthetic D2A21 used as structural benchmarks. RP557 possesses broad spectrum activity against Gram-positive and Gram-negative bacteria and fungi, including recalcitrant biofilm with substantial selective killing over bacterial cells compared to mammalian cells. RP557 did not induce resistance following chronic passages of Pseudomonas aeruginosa and Staphylococcus aureus at subinhibitory concentrations, whereas concurrently run conventional antibiotics, gentamycin, and clindamycin, did. Furthermore, RP557 was able to subsequently eliminate the generated gentamycin resistant P. aeruginosa and clindamycin resistant S. aureus strains without requiring an increase in minimum inhibitory concentration (MIC) concentrations. RP557 was evaluated further in a MRSA murine wound abrasion infection model with a topical application of 0.2% RP557, completely eliminating infection. If these preclinical results are translated into the clinical setting, RP557 may become crucial for the empirical broad-spectrum treatment of wound pathogens, so that infections can be reduced to a preventable complication of combat-related injuries.

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

“…In contrast, bactericidal antibiotics cause cell death (Schwalbe et al, 2007). Several studies have suggested that in general terms, bacteriostatic and bactericidal activities can be linked to MOA (Finberg et al, 2004;Woodburn et al, 2019;Yasir et al, 2019), though exceptions exist (Finberg et al, 2004). In the following, we present methods to determine the bactericidal activity of HDPs, as well as methods to look at membrane perturbation.…”

Designed Antimicrobial Peptides for Topical Treatment of Antibiotic Resistant Acne Vulgaris

“…Therefore, a monotherapy acne treatment that is highly potent with a reduced likelihood of developing antimicrobial resistance and with anti-inflammatory activity is urgently needed. Designed antimicrobial peptides (dAMPs) are laboratory synthesized peptides that are rationally designed analogs of naturally occurring AMPs, which provide the first line of defense against invading pathogens in all multicellular organisms [8][9][10]. dAMPs, also known as host defense peptides, have direct antibiotic activities in addition to modulating immune responses [8].…”

Designed Antimicrobial Peptides Against Trauma-Related Cutaneous Invasive Fungal Wound Infections

“…Fungi and bacteria do not develop resistance against the dAMPs [16][17][18]. The rapid destruction of pathogenic cells by dAMPs infers a theoretical reduced likelihood of developing bacterial resistance.…”