The Pharmacodynamics Study of Insect Defensin DLP4 Against Toxigenic Staphylococcus hyicus ACCC 61734 in Vitro and Vivo.

Xuanxuan Ma,Ruoyu Mao,Da Teng,Na Yang,Ya Hao,Xue Yan,Jianhua Wang

doi:10.3389/fcimb.2021.638598

Abstract

Staphylococcus hyicus (S. hyicus), as the main pathogen of exudative epidermitis (EE) in piglet, can cause a wide variety of diseases, ranging from bovine mastitis, chicken arthritis and even human sepsis, which has brought serious threats to animals and human. The potential threat of S. hyicus infection to both public and animal health has aroused great concern. The aim of our study was to explore the efficacy of insect defensin DLP4 against S. hyicus ACCC 61734 in vitro and in vivo. The in vitro efficacies of DLP4 against S. hyicus ACCC 61734 showed high antibacterial activity (0.92 μM), a long postantibiotic effect (9.54 h), a synergistic effect with ceftriaxone, penicillin and amoxicillin, a stable bacteriostatic effect, and intracellular bacteriostatic activity against S. hyicus ACCC 61734 in HaCaT cells. Besides, the antibacterial mechanism of DLP4 against S. hyicus ACCC 61734 was explored for the first time, which indicated that the antibacterial effect of DLP4 was related to its ability to destroy cell wall and generate membrane vesicles. The in vivo therapeutic effect of DLP4 was evaluated through mouse abscess model, and the results showed that DLP4 could effectively alleviate the mouse skin abscess by inhibiting bacterial proliferation and regulating cytokines. This study first demonstrated that DLP4 may be a promising therapeutic agent against S. hyicus ACCC 61734 infection.

Highlights

Exudative epidermitis (EE), known as “greasy pig disease”, is an occasional and contagious skin disease, which predominantly infects weaning and newborn piglet (Olivry and Linder, 2009)
The results indicated that DLP4, as the promising antimicrobial agent, displayed more potent antibacterial activity against S. hyicus
S. hyicus ACCC 61734 cells decreased dramatically after treatment with DLP4, and the bacteria were inhibited completely after treatment with 4× minimum inhibitory concentrations (MICs) DLP4 for 1 h and 2× MIC DLP4 for 2 h, and the bacteria were temporarily inhibited after treatment with 1× MIC DLP4 for 2 h but regrew after 12 h, which demonstrated that DLP4 has dose-dependent growth inhibition against S. hyicus ACCC 61734

Summary

Introduction

Exudative epidermitis (EE), known as “greasy pig disease”, is an occasional and contagious skin disease, which predominantly infects weaning and newborn piglet (Olivry and Linder, 2009). Staphylococcus hyicus was widely acknowledged as the major causative agent of EE, it can produce up to six various 27–30 KDa exfoliation toxins (ExhA, ExhB, ExhC, ExhD, ShetA, and ShetB), which was always considered as the key pathogenic factor of EE (Andresen et al, 1993; Andresen and Ahrens, 2004). Given the increasing acquisition of antibiotic resistance by pathogens, the prevention and control of S. hyicus infection have been a huge challenge, which indicates an urgent need for new effective antibacterial drugs. DLP4 was difficult to develop resistance due to its unique antibacterial mechanism (Li et al, 2017) All these results indicated that DLP4 may be considered to be a promising drug for treating S. hyicus infections

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