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.
Highlights
Multidrug resistant bacteria, such as Staphylococcus aureus (MRSA), severely limits the effectiveness of antibiotics [1,2]
A significant survival rate reduction was observed in C. elegans infected with MSSA and MRSA
After 96 h of observation, the results showed that all of the 13 antimicrobial peptides had a therapeutic effect on the methicillin-resistant S. aureus infected group in comparison with the control group
Summary
Multidrug resistant bacteria, such as Staphylococcus aureus (MRSA), severely limits the effectiveness of antibiotics [1,2]. MRSA has the highest mortality rate among multidrug resistant bacteria [3] and affects a variety of hosts, both human and animal [4]. One method of overcoming resistance is the development of new anti-infective agents that activate the host’s natural immune defenses against pathogens [5,6]. A series of strategies has been adopted to test new anti-infective agents in whole animal models such as Caenorhabditis elegans (C. elegans) [7]. The common screening method for new drugs using C. elegans is widely recognized by researchers [8], the drug screening still focuses on the level of individual behavior (physiological indicators, mortality, etc.) in nematode infection models. The current understanding is that a continued increase of host-pathogen interactions and bacterial pathogenesis relies on the feedback of the innate immunity system to the external stimuli as a key link in most drug screening studies [9]
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