Passive immunization against methicillin resistant Staphylococcus aureus recombinant PBP2a in sepsis model of mice: Comparable results with antibiotic therapy

Int Immunopharmacol. 2018 Mar:56:186-192. doi: 10.1016/j.intimp.2018.01.035. Epub 2018 Feb 3.

Abstract

Methicillin resistant Staphylococcus aureus (MRSA) is a representative pathogen that is responsible for a nosocomial infection and considerable yearly mortality rate. Antibiotic resistance provides a great reason for immunotherapy as an alternative strategy to prevent and/or treat the infection. Herein, following the preparation of recombinant penicillin binding protein 2a (r-PBP2a), rabbit polyclonal IgG was purified. Specificity of IgG to r-PBP2a was evaluated by ELISA and western blotting. IgG fraction was prepared by sulfate ammonium precipitation. In addition opsonophagocytosis assay confirmed bioactivity of purified IgG. Experimental mice were challenged with lethal dose of MRSA (5 × 108) and mortality rate was recorded in the mice treated with IgG fraction for anti-rPBP2a, normal rabbit IgG, vancomycin therapy, and PBS control group. Bacterial quantity was evaluated by culture of liver, kidney and spleen homogenates. Results showed that passive immunization with anti r-PBP2a resulting in a significant improvement in survival rate as well as vancomycin treatment compared with control groups. Furthermore, anti r-PBP2a IgG enhanced considerably the phagocytosis of the S. aureus COL strain, reduced bacterial load, and inhibited the systemic spread of COL strain to the internal organs. These results confirmed that passive immunization by anti-r-PBP2a plays a considerable role in the control of infections caused by S. aureus similar to that of antibiotic therapy.

Keywords: Methicillin-resistant Staphylococcus aureus; PBP2a; Passive immunization.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Epitopes / immunology*
  • Female
  • Immunization, Passive
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Immunotherapy
  • Methicillin-Resistant Staphylococcus aureus / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / immunology*
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*
  • Sepsis / drug therapy
  • Sepsis / immunology*
  • Staphylococcal Infections / immunology*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Epitopes
  • Immunoglobulin G
  • Penicillin-Binding Proteins
  • Recombinant Proteins
  • mecA protein, Staphylococcus aureus