Bacterial-Specific Aggregation and Killing of Immunomodulatory Host Defense Peptides.

Nauman Nazeer,Juan Carlos Rodriguez-Lecompte,Marya Ahmed

doi:10.3390/ph14090839

Nauman Nazeer, Juan Carlos Rodriguez-Lecompte + Show 1 more

Open Access

https://doi.org/10.3390/ph14090839

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Abstract

This study involves the design and development of disulfide bridge-linked antimicrobial peptides using the host defense protein Angiogenin 4 (chAng4) as a template. The mini peptides derived from chAng4 (mCA4s) were evaluated for their antibacterial efficacies in various pathogenic bacterial strains, and the role of the oxidation state of thiols in the peptide sequence and its implication on antibacterial properties were explored. A remarkable property of these synthetic mCA4 peptides is their capability to flocculate bacteria and mediate bacterial-specific killing, in the absence of any other external stimulus. mCA4s were further evaluated for their cellular uptake, hemolytic activities, toxicities, and immunomodulatory activities in different eukaryotic cell lines. The results indicate that disulfide bridge-containing cationic amphipathic peptides show superior antibacterial efficacies, are nontoxic and nonhemolytic, and mediate bacterial flocculation and killing, in the absence of external stimuli.

Highlights

Host defense peptides (HDPs) are low-molecular-weight (2–50 kDa) fragments of proteins that are present in the innate immune system of a variety of organisms including plants, insects, bacteria, fungi, and viruses, as a first line of defense against microbial infections [1]
The synthetic short peptide sequences (
The hydrophilic cationic peptides were purified by precipitation in organic solvent and exhibited reduced purity (Supplementary Figure S1)

Summary

Introduction

Host defense peptides (HDPs) are low-molecular-weight (2–50 kDa) fragments of proteins (made up of 12–50 amino acids) that are present in the innate immune system of a variety of organisms including plants, insects, bacteria, fungi, and viruses, as a first line of defense against microbial infections [1]. Truncated derivatives of larger HDPs have been reported to lose antibacterial activity at smaller sizes and lower cationic charges [6,7,8,9,10,11,12,13,14,15]. Most of these bacterial-selective peptides engineered by fusing multiple peptide sequences are, much larger in size (>15 amino acids) and are not a cost-effective option as antimicrobial agents. The engineered peptides self-assemble in the presence of S. aureus

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