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 are performed 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 analyses 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.

Comparative in silico analyses of proteins involved in serum resistance as promising vaccine candidates against Acinetobacter baumannii

“…A soluble and stable globular domain in C-terminal of the protein interacts with the peptidoglycan layer in the periplasmic space and it is required for the integrity of the cell [36]. Multiple sequence alignments of beta-barrel domain showed L4 was conserved while L1, L3, and L2 had more amino acid changes [29]. The extracellular loops are functional and dynamic regions of this protein which could be involved in adherence, invasiveness, biofilm formation, apoptosis, immune stimulation, iron metabolism and serum resistance.…”

“…These following procedures were performed only for AbOmpA and PKF, as promising vaccine targets. Data have shown that the beta-barrel domain of AbOmpA is similar to beta-barrel domain of Klebsiella pneumoniae OmpA (PDB accession number is 2K0L) [29]. This domain has 4 extracellular loops.…”