A Novel Amphibian Antimicrobial Peptide, Phylloseptin-PV1, Exhibits Effective Anti-staphylococcal Activity Without Inducing Either Hepatic or Renal Toxicity in Mice

Abstract

In order to part address the problem of drug-resistant pathogens, antimicrobial peptides (AMPs) have been proposed as alternatives to traditional antibiotics. Herein, a novel phylloseptin peptide, named phylloseptin-PV1 (PPV1), is described from the defensive skin secretion of the Neotropical white-lined leaf frog, Phyllomedusa vaillantii. The peptide was synthesized by solid phase peptide synthesis (SPPS) and purified by RP-HPLC, prior to assessment of its biological activities. PPV1 not only demonstrated potent antimicrobial activity against planktonic ESKAPE microorganisms and the yeast, Candida albicans, but also inhibited and eradicated Staphylococcus aureus and MRSA biofilms. The antimicrobial mechanism was shown to include permeabilization of target cell membranes. The in vivo antimicrobial activity of the peptide was then evaluated using mice. PPV1 also exhibited antiproliferative activity against the cancer cell lines, H157, MCF-7, and U251MG, but had a lower potency against the normal cell line, HMEC-1. Although, the peptide possessed a moderate hemolytic action on mammalian red blood cells in vitro, it did not induce significant hepatic or renal toxicity in injected infected mice. These studies have thus found PPV1 to be a potent phylloseptin group AMP, which can effectively inhibit staphylococci, both in vitro and in vivo, without eliciting toxicity. These data thus provide support for further evaluation of PPV1 as a novel antimicrobial agent with therapeutic potential.

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

“…A wide spectrum of antimicrobial activities of AMPs inspires researchers to search for new active peptides in biological material [ 252 , 253 ], and also serves as the basis for the design of new synthetic compounds [ 254 , 255 ]. To date, information about AMPs is presented in numerous databases describing the structural, functional, allergenic and toxicological properties of these peptide factors of innate immunity [ 256 , 257 , 258 , 259 , 260 ].…”

Targeted Modification and Structure-Activity Study of GL-29, an Analogue of the Antimicrobial Peptide Palustrin-2ISb

“…Moreover, GL-29 and GL-22 exhibited strong potency against the two tested clinical strains, including the cystic fibrosis (CF) isolated strains, S. aureus (B042 V2E1 A) and MRSA (B038 V1S1 A) [ 31 ]. Moreover, these two peptides possessed extraordinary activities against KPC-producing strains, including E. coli (ATCC BAA-2340) and K. pneumoniae (ATCC BAA-1705), which made them valuable for further studies [ 38 , 39 ]. In addition, it is widely accepted that the antibacterial mechanism of AMPs is the membrane permeabilisation mode of action [ 40 ].…”

Multiple roles of ribosomal antimicrobial peptides in tackling global antimicrobial resistance

“…Broad-spectrum activity, diversity of mechanisms, fast action, lower risk of resistance and low propensity to develop toxicity are some of the most notable advantages [ 248 ]. Interestingly, in contrast to the high toxicity of available polypeptide antibiotics, many recent in vivo studies have reported that AMPs are safe for animal models [ 70 , 223 , 249 ]. Notably, by testing the lysis of human renal proximal tubular epithelial cells (HRPTEC) in vitro and applying some sequence modifications, the possibility of reduced renal function can be avoided both in vitro and in vivo [ 70 ].…”