Abstract

Staphylococcus hyicus is recognized as a leading pathogen of exudative epidermitis in modern swine industry. Antimicrobial peptides are attractive candidates for development as potential therapeutics to combat the serious threats of the resistance of S. hyicus. In this study, a series of derivatives were designed based on the NZ2114 template with the aim of obtaining peptides with more potent antimicrobial activity through changing net positive charge or hydrophobicity. Among them, a variant designated as NZL was highly expressed in Pichia pastoris (P. pastoris) with total secreted protein of 1505 mg/L in a 5-L fermenter and exhibited enhanced antimicrobial activity relative to parent peptide NZ2114. Additionally, NZL could kill over 99% of S. hyicus NCTC10350 in vitro within 8 h and in Hacat cells. The results of membrane permeabilization assay, morphological observations, peptide localization assay showed that NZL had potent activity against S. hyicus, which maybe kill S. hyicus through action on the cell wall. NZL also showed an effective therapy in a mouse peritonitis model caused by S. hyicus, superior to NZ2114 or ceftriaxone. Overall, these findings can contribute to explore a novel potential candidate against S. hyicus infections.

Highlights

  • Staphylococcus hyicus is one of the opportunistic and commensal pathogens which can cause acute infections to animals and humans

  • It was reported that exfoliative toxinsproducing S. hyicus is primarily known as the most common causative agent of exudative epidermitis in pigs, which occurs typically as an acute skin lesions characterized by sebaceous exudation, exfoliation, and vesicle formation

  • Piglets infected with S. hyicus are frequently treated with antibiotics, but treatment failure is common due to the emergence of drug-resistant S. hyicus and the limited number of antimicrobial drugs available for treating exudative epidermitis

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Summary

Introduction

Staphylococcus hyicus is one of the opportunistic and commensal pathogens which can cause acute infections to animals and humans. It was reported that exfoliative toxinsproducing S. hyicus is primarily known as the most common causative agent of exudative epidermitis in pigs, which occurs typically as an acute skin lesions characterized by sebaceous exudation, exfoliation, and vesicle formation. This disease with prominent morbidity and mortality occurs worldwide, resulting in considerable economic losses in the swine industry [1,2,3,4]. Studies have demonstrated that S. hyicus frequently develops resistance to antimicrobial agents in different countries [5,6,7].

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