Staphopain mediated virulence and antibiotic resistance alteration in co-infection of Staphylococcus aureus and Pseudomonas aeruginosa: an animal model

BMC Biotechnol. 2024 Mar 4;24(1):10. doi: 10.1186/s12896-024-00840-x.

Abstract

Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.

Keywords: Pseudomonas aeruginosa; Staphylococcus aureus; Co-infection; Cysteine protease; Enzyme therapy; Enzymes; Recombinant; Staphopain A.

MeSH terms

  • Animals
  • Coinfection* / drug therapy
  • Drug Resistance, Microbial
  • Models, Animal
  • Pseudomonas aeruginosa / genetics
  • Staphylococcus aureus / genetics
  • Virulence
  • Virulence Factors / genetics
  • Wound Infection* / drug therapy

Substances

  • Virulence Factors