A frog‐derived antimicrobial peptide as a potential anti‐biofilm agent in combating Staphylococcus aureus skin infection

Abstract

Staphylococcus aureus (S. aureus), one of the most prevalent bacteria found in atopic dermatitis lesions, can induce ongoing infections and inflammation by downregulating the expression of host defence peptides in the skin. In addition, the emergence of the ‘superbug’ Methicillin‐resistant S. aureus (MRSA) has made the treatment of these infections more challenging. Antimicrobial peptides (AMPs), due to their potent antimicrobial activity, limited evidence of resistance development, and potential immunomodulatory effects, have gained increasing attention as potential therapeutic agents for atopic dermatitis. In this study, we report a novel AMP, brevinin‐1E‐OG9, isolated from the skin secretions of Odorrana grahami, which shows potent antibacterial activity, especially against S. aureus. Based on the characteristics of the ‘Rana Box’, we designed a set of brevinin‐1E‐OG9 analogues to explore its structure–activity relationship. Brevinin‐1E‐OG9c‐De‐NH2 exhibited the most potent antimicrobial efficacy in both in vitro and ex vivo studies and attenuated inflammatory responses induced by lipoteichoic acid and heat‐killed microbes. As a result, brevinin‐1E‐OG9c‐De‐NH2 might represent a promising candidate for the treatment of S. aureus skin infections.

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

“…vCPP2319, a polycationic peptide derived from the Torque virus capsid protein, exhibited activity against established biofilms by killing biofilm embedded bacteria but had no effect on the EPS matrix [66]. The frog skin-derived AMP brevinine-1E-OG9, its analogue (brevinine-1E-)OG9c-De-NH2 [67], and temporin G [68] as well as the synthetic AMP SAMP-A4-C8 not only effectively inhibited and eradicated biofilms but also killed the dormant persister cells, herewith counteracting the recalcitrance of S. aureus infections [69]. Both AP7121, produced by E. faecalis CECT7121 [70], and in silico designed 1018-k6 [71] dose-dependently inhibited biofilm formation on inert surfaces.…”

Staphylococcus aureus and biofilms: transmission, threats, and promising strategies in animal husbandry

“…Although the current autonomous design of modified AMPs is not yet perfect, its feasibility has been demonstrated. S. aureus , one of the most prevalent bacteria found in dermatitis lesions, can induce ongoing infections and inflammation by downregulating the expression of host defence peptides in the skin [ 86 ]. Hagfish intestinal peptides effectively inhibited MRSA in vitro and in vivo [ 87 ].…”

A promising antibiotic candidate, brevinin-1 analogue 5R, against drug-resistant bacteria, with insights into its membrane-targeting mechanism

“…At different time intervals, the mixture was diluted in PBS and spotted on the agar plate. The surviving colonies were counted the next day [10]. Each test was repeated three times.…”

“…Amphibians are typically exposed to intricate environments teeming with diverse microorganisms, and while they possess adaptive immune systems, these are not as robust as those of mammals [6][7][8]. Research on amphibian-derived AMPs has unveiled their substantial pharmacological values, including remarkable antimicrobial efficacy, broad-spectrum antimicrobial properties, and host immunity modulation, which positions them as promising candidates for a novel generation of antibiotic agents [9,10]. Meanwhile, unlike conventional antibiotics that rely on specific targets to achieve therapeutic effects, most AMPs exert their antimicrobial actions by targeting bacterial membranes, which makes it energetically costly for bacteria to acquire resistance through mutation [11,12].…”

“…As one of the most influential AMP families in frogs, brevinin-1 peptides have been reported to have potent antimicrobial properties against planktonic bacteria, biofilms, and even antibiotic-resistant cells [10,18,19]. The further development of brevinins as antibiotic agents, however, has primarily been hindered by their high haemolytic activity [18].…”