Brevinin-2 Drug Family—New Applied Peptide Candidates Against Methicillin-Resistant Staphylococcus aureus and Their Effects on Lys-7 Expression of Innate Immune Pathway DAF-2/DAF-16 in Caenorhabditis elegans

Abstract

The issue of Staphylococcus aureus (MRSA) developing a resistance to drugs such as methicillin has long been the focus for new drug development. In recent years, antimicrobial peptides, such as small molecular peptides with broad-spectrum antibacterial activity and special antibacterial mechanism, have shown a strong medicinal potential. In particular, the Brevinin-2 family has been shown to have a significant inhibitory effect against gram-positive bacteria (G+). In this study, we researched the influence of MRSA on the behavior and survival rate of nematodes. We established an assay of Caenorhabditis elegans–MRSA antimicrobial peptides to screen for new potent anti-infective peptides against MRSA. From the Brevinin-2 family, 13 peptides that had shown strong effects on G+ were screened for their ability to prolong the lifespan of infected worms. Real-time Polymerase Chain Reaction (PCR) tests were used to evaluate the effect on the innate immune pathway dauer formation defective (DAF)-2/DAF-16 of C. elegans. The assay successfully screened and filtered out four of the 13 peptides that significantly improved the survival rate of MRSA-infected worms. The result of real-time PCR indicated that the mRNA and protein expression levels of lys-7 were consistently upregulated by being treated with four of the Brevinin-2 family. The Brevinin-2 family peptides, including Brevinin-2, Brevinin-2-OA3, Brevinin-2ISb, and Brevinin-2TSa, also played an active role in the DAF-2/DAF-16 pathway in C. elegans. We successfully demonstrated the utility of anti-infective peptides that prolong the survival rate of the MRSA-infected host and discovered the relationship between antibacterial peptides and the innate immune system of C. elegans. We demonstrated the antimicrobial effects of Brevinin-2 family peptides, indicating their potential for use as new drug candidates against MRSA infections.

Antimicrobial Peptide Brevinin-2isb, New Drug Candidates Enhance the Innate Immune Response and Cured Caenorhabditis Elegans With Methicillin-Resistant Staphylococcus Aureus (MRSA)

“…In previous studies [10] , a four-day continuous determination of gene expression was then conducted in order to further study the effect of the peptides on MRSA inhibition and the effect of DAF-2/DAF-16 on the immune system of C. elegans. Brevinin-2-OA3,Brevinin-2ISb, and Brevinin-2TSa significantly up-regulated both the mRNA and protein levels of the key antimicrobial gene lys-7 in the DAF-2/DAF-16 pathway during 24-96 h. In this study ,we had firstly found in this work that Brevinin-2ISb was observed to extend the life span of infected and non-infected nematodes as well as enhance the expression of the tested immune response genes of adult worms, again suggesting an important role of Brevinin-2ISb in the positive modulation of immunity in the animals.…”

Generation of truncated derivatives through in silico enzymatic digest of peptide GV30 target MRSA both in vitro and in vivo

“…Since the first brevinin-2 peptide was extracted from the skin secretion of the frog, Rana brevipoda porsa, in 1992, the brevinin-2 family has gradually entered the researcher's field of vision [16] . The brevinin-2 family has noticeable inter-species and intra-species structural differences [17] . Unlike other families with obvious conserved sequences, the brevinin-2 family has four conserved amino acids (Lys15, Cys27, Lys28 and Cys33) [18] .…”