Immunoprotective potential of BamA, the outer membrane protein assembly factor, against MDR Acinetobacter baumannii

Sci Rep. 2017 Sep 29;7(1):12411. doi: 10.1038/s41598-017-12789-3.

Abstract

Acinetobacter baumannii infections are responsible for major health problems in immunocompromised patients particularly in intensive care units. Due to rapid acquisition of and also inherent drug resistance, a vaccine is an effective treatment option against this pathogen. BamA, an outer membrane β-barrel assembly protein, was identified in A. baumannii as potential vaccine candidate by in silico analysis. The immunoprotective efficacy of this highly conserved protein was investigated against a virulent multidrug resistant clinical isolate using murine pneumonia model. Recombinant BamA elicited a high IgG antibody titer (160000) in mice. Opsonophagocytic killing assay showed non-neutrilizing, opsonizing antibodies with combinatorial bactericidal activity of antibodies and complement components. Active and passive immunization protected 80 and 60% mice respectively against intranasal challenge with lethal dose (109 CFU) of virulent A. baumannii along with efficient clearance of bacteria in mice lungs and reduction in levels of pro-inflammatory cytokines viz. TNF-α, IL-6 and IL-1β in sera and lung tissue homogenate. Increase in levels of IL-10, an anti-inflammatory cytokine and reduction of neutrophils in lungs facilitated the control of infection. This study demonstrates the potential of BamA as effective vaccine candidate and a promising target for antibody-based therapy to protect against MDR A. baumannii infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / immunology*
  • Acinetobacter baumannii / immunology*
  • Animals
  • Antibodies, Bacterial / immunology*
  • Bacterial Load
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / immunology*
  • Cytokines / immunology
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial
  • Immunization / methods
  • Immunoglobulin G / immunology
  • Lung / microbiology
  • Mice, Inbred BALB C
  • Pneumonia, Bacterial / immunology
  • Recombinant Proteins / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Cytokines
  • Immunoglobulin G
  • Recombinant Proteins