In-silico prediction and modeling of ApxA exotoxins of Actinobacillus pleuropneumoniae: ApxIA, -IIA, -IIIA and -IVA
Background. Actinobacillus pleuropneumonia is a gram-negative bacterium that serves as the major etiological agent for porcine pleuropneumonia, one of critical diseases causing substantial socio-economic losses in swine rearing industry world-wide. Apx exotoxins are the members of RTX-toxin family secreted by gram-negative bacteria that facilitates Type-I Secretion System (T1SS), reported as the major virulence factor in the pathogenesis. This study was conducted to demonstrate successful
... perimental approach by predicting the tertiary structures of ApxA exotoxins and further characterizing their structural and functional annotations via application of appropriate in silico methods. Methods. The sequences of ApxA exotoxins were retrieved from the National Centre for Biotechnology Information database (NCBI) for bioinformatics analyses in this study. ApxA exotoxins were subjected to several computational analyses to characterize in different aspects. I-TASSER and Phyre2 servers were used to predict 3-D structures of ApxA toxins which were further validated by ProSA and SAVES servers. Antigenic epitopes of each ApxA exotoxin were predicted using the BepiPred 2.0 program. Results. Based on predictions on secondary structure compositions, hydropathicity, domain boundaries, tertiary structures and their structural analogs, ApxIA, -IIA and –IIIA shared remarkable resemblance in structural and functional aspects while ApxIVA exhibited distinct and complex characteristics. Discussion. 3-D modeling of ApxA exotoxins were executed to best interpret the proteins in their structure and functions to gain novel insights of their pathogenesis. The domain-wise interpretation of the proteins indicates the likely roles of each toxin with conjectured antigenic epitopes. The structural and functional annotations suggested in this study via in silico predictive approach may provide insights to prevent and control A. pleuropneumoniae by development of diagnostic methods and vaccine candidates.