Abstract

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

Highlights

  • Staphylococcus aureus (S. aureus) is a major human pathogen associated with increased morbidity, mortality, and excess hospital costs [1,2]

  • The 3% DPTM ointment treated group had the bacterial count lowered by 1.05 log compared to 2% DPTM ointment treated group (p < 0.01), but only lowered by 0.63 log compared to retapamulin ointment treated group

  • This study evaluated the potent antibacterial activities of DPTM, a derivative of pleuromutilin, against Methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and against MRSA ATCC43300 in a murine skin wound model

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Summary

Introduction

Staphylococcus aureus (S. aureus) is a major human pathogen associated with increased morbidity, mortality, and excess hospital costs [1,2]. It causes skin and soft tissue infections (SSTI), including impetigo, folliculitis, furuncles, and subcutaneous abscesses [3,4]. Methicillin-resistant Staphylococcus aureus (MRSA) has aroused a growing concern and became a significant public health threat. Decreased susceptibility and even resistance to vancomycin, daptomycin, linezolid, and other antibiotics, have been reported in many parts of the world [7,8,9]. There is pressing need to develop novel antibiotics with unique mechanism of action against this dreadful pathogen

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