Molecular analysis of AbOmpA type-1 as immunogenic target for therapeutic interventions against MDR Acinetobacter baumannii infection

Abstract

Introduction: Acinetobacter baumannii is associated with hospital-acquired infections. Outer membrane protein A of A.baumannii (AbOmpA) is a well-characterized virulence factor which has important roles in pathogenesis of this bacterium. Methods: Based on our PCR-sequencing of ompA gene in the clinical isolates, AbOmpA protein can be categorized into two types, named here type-1 and type-2. We preformed in silico analyses on beta-barrel domain of AbOmpA such as sequence alignments, prediction of 3D modeling and immunoinformatics. Results: High prevalence of AbOmpA type-1 were detected both in 21 multidrug-resistant (MDR) A. baumannii isolates collected from clinical settings (64% of total sequences) and in silico sequences extracted from Uniprot database (49.7% of total sequences). Multiple sequence alignments and phylogenic tree revealed AbOmpA sequences in comparison with OmpA of Enterobacteriaceae family were more heterogenic, especially at extracellular loops amino acid positions and were evolutionary far from this family. Characterization of in silico 3D molecular model of beta-barrel domain of AbOmpA type-1 showed this domain had four large extracellular loops which resemble to beta-barrel domain of Klebsiella pneumonia OmpA (KpOmpA). Immunoinformatics analyses showed the four extracellular loops had high scores as B and T cell antigenic epitopes especially in loop-1 and 3. Geometry analysis revealed extracellular loops effectively protrude to outer space of the cell. Conclusion: Beta-barrel domain of AbOmpA type-1 has all the characteristics of a promising vaccine and could be considered as an excellent target for a vaccine against MDR A. baumannii infection.

Keywords

• beta-barrel domain of abompa
• alignment
• phylogenic tree
• in silico 3d molecular model
• epitope prediction