Enhanced immunoprotection against Acinetobacter baumannii infection: Synergistic effects of Bap and BauA in a murine model.

BACKGROUND: The rise of multi-drug resistant Acinetobacter baumannii poses a grave threat to hospital settings, resulting in increased mortality rates and garnering global attention. The formation of biofilms facilitated by biofilm-associated protein (Bap) and the iron absorption capabilities mediated by Baumannii acinetobactin utilization A (BauA) contribute to the persistence and survival of multidrug-resistant strains. In this study, we aimed to investigate the potential of disrupting the function of BauA and Bap simultaneously as a strategy for controlling A. baumannii. METHODS: Recombinant Bap and BauA were expressed, purified, and subcutaneously administered individually and in combination to BALB/c mice. Subsequently, mice were intraperitoneally challenged with A. baumannii, and the bacterial load and tissue damage in the spleen, lung, and liver were assessed. Serum samples were evaluated to determine antibody titers in surviving mice. RESULTS: Specific IgG antibodies were significantly increased. A combination of the antigens resulted in enhanced titer of specific IgGs in comparison to either BauA or Bap alone. The antibodies remained stable over a seven-month period. The combination of Bap and BauA exhibited superior immunoprotection against A. baumannii infection compared to individual administration, resulting in a further reduction in bacterial load in the liver, spleen, and lungs. The histopathological analysis demonstrated successful protection of the tissues against A. baumannii-induced damage upon administration of the two immunogens. CONCLUSIONS: The combination of Bap and BauA has the potential to target a broader range of A. baumannii strains, including those expressing either Bap or BauA, thereby increasing its efficacy against a diverse array of strains.

Synergistic immunoprotection by Oma87 and Bap against Acinetobacter baumannii sepsis model.

Acinetobacter baumannii is the leading cause of nosocomial infection. A surface protein commonly known as biofilm associate protein (Bap) has been identified in a bloodstream isolate of A. baumannii. Bap of A. baumannii is involved in intercellular adhesion within the mature biofilm. Outer membrane protein Acinetobacter 87 kDa (Oma87) or ß-barrel assembly machinery A (BamA) has been introduced as an immunogenic outer membrane protein via in silico reverse vaccinology. Current research examines the synergistic effect of immunization of mice with both recombinant proteins viz., Oma87 and Bap. Antibodies were raised to the proteins. The mice were challenged with A. baumannii ATCC 19606 and the bacterial burden was enumerated in the mice's livers, spleens, and lungs followed by histological examination. IgG levels significantly increased, and a significant (p < 0.0001) difference was observed between bacterial burdens in the internal organs of the actively and passively immunized groups. Female BALB/c mice weighing 20-25 g, were divided into 4 groups of 14 mice each viz., control, Oma87, Bap, Oma87-Bap groups. The proteins were individually immunogenic, but the combination of both proteins had a synergistic protection property. This is further supported by the histological examination. Based on the results, the combination of Oma87 and Bap may be considered a promising vaccine candidate against A. baumannii .