Housefly Phormicin inhibits Staphylococcus aureus and MRSA by disrupting biofilm formation and altering gene expression in vitro and in vivo

Int J Biol Macromol. 2021 Jan 15:167:1424-1434. doi: 10.1016/j.ijbiomac.2020.11.096. Epub 2020 Nov 14.

Abstract

The increasing drug resistance of pathogenic bacteria is a crisis that threatens public health. Antimicrobial peptides (AMPs) have been suggested to be potentially effective alternatives to solve this problem. Here, we tested housefly Phormicin-derived peptides for effects on Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) infections in vitro and in vivo. A decreased bacterial load of MRSA was observed in the mouse scald model after treatment with Phormicin and in the positive control group (vancomycin). A mouse scrape model indicated that Phormicin helps the host fight drug-resistant MRSA infections. The protective effect of Phormicin on MRSA was confirmed in the Hermetia illucens larvae model. Phormicin also disrupted the formation of S. aureus and MRSA biofilms. Furthermore, this effect coincided with the downregulation of biofilm formation-related gene expression (agrC, sigB, RNAIII, altA, rbf, hla, hld, geh and psmɑ). Notably, virulence genes and several regulatory factors were also altered by Phormicin treatment. Based on these findings, housefly Phormicin helps the host inhibit MRSA infection through effects on biofilm formation and related gene networks. Therefore, housefly Phormicin potential represents a candidate agent for clinical MRSA chemotherapy.

Keywords: Antimicrobial peptide; Biofilm formation; Musca domestica; Phormicin.

MeSH terms

  • Aldehyde Oxidoreductases / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / chemistry
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects*
  • Body Weight
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Gene Expression Regulation, Bacterial / drug effects
  • Houseflies / chemistry*
  • Humans
  • Larva / drug effects
  • Larva / growth & development
  • Larva / microbiology
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Microscopy, Electron, Scanning
  • RNA, Bacterial / metabolism
  • Sigma Factor / metabolism
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / physiology
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • RNA, Bacterial
  • RNAIII, Staphylococcus aureus
  • SigB protein, Bacteria
  • Sigma Factor
  • Vancomycin
  • Aldehyde Oxidoreductases
  • argC protein, Bacteria