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.