Inhibition of Oligomerization of Aerolysin from Aeromonas Hydrophila: Homology Modeling and Docking Approach for Exploration of Hemorrhagic Septicemia

Abstract

Aerolysin (Aer) is a pore forming toxin that plays important role in pathogenesis of Aeromonas hydrophila which causes hemorrhagic septicemia in aquatic and terrestrial animals including humans. Aerolysin aggregates in the forms of oligomers on the surface of animal RBCs and its ability to bind with Glycosylphosphatidyl inositol (GPI) anchored protein receptor. The primers were designed for Aer gene and amplified to target the complete ORF of Aeromonas hydrophila; later it was sequenced. Homology modeling was used to construct the 3-D structure of Aer using known template (PDB: 1PRE) and the stereochemical quality, torsion angle of 3-D structure was validated. Several drugs were used for virtual screening through molecular docking and four drugs viz. Aralia, Gypsogenin, Saponin and TS-saponin are more potent for inhibition of oligomerization of aer through robust binding affinity between protein-drug interactions. The phylogenetic analysis showed that homology of Aer present in A. hydrophila resembled with other bacteria. The findings could help as a beginning in rationale designing of novel drugs and its analogs.

A Potential Screening of Peptide Deformylase Inhibitors Towards the Control of Aeromonas hydrophila

“…All the above properties of peptide deformylase satisfied the need for good quality of the 3-D model. The previous study also supported our data regarding the quality of the 3-D model and the amino acids present in allowed region of the Ramachandran plot [10,31,38].…”

“…The effectiveness of actinonin against PDF of E. coli and Staphylococcus aureus has been further tested and it has been found that similar concentrations could control the growth of both bacteria [35]. Molecular docking has been used for the screening of potent drug molecules by targeting the aerolysin of A. hydrophila [38] and 3-oxoacyl-acyl carrier protein synthase II of Mycobacterium tuberculosis [56]. Sharma et al [57] have tested BB-3497 and actinonin and both were found to be potent drugs against the PDF of M. tuberculosis at low concentrations.…”

“…In addition, Küpfer et al [60] have used gyrB and rpoB sequences for construction of phylogeny of Aeromonas species. In a relevant study, a phylogenetic tree has been constructed using the aerolysin and hemolysin protein sequences of A. hydrophila and they have identified a similarity among Aeromonas species and other pathogenic bacteria [10,38]. …”

“…Currently, there is no 3-D structure of PDF of A. hydrophila available yet. The homology modeling was used to generate a 3-D model of hemolysin and aerolysin of A. hydrophila [10,38]. Recently, Fazil et al [39] used homology modeling for generating a 3-D model of histidine kinase of A. hydrophila.…”

“…In addition, they have also used 16S rDNA variable regions for genetic relationship analysis [39]. A number of proteins sequences such as hemolysin, aerolysin and DNA gyrase of A. hydrophila have been used for phylogenetic analysis [10,31,38]. The housekeeping genes rpoD and gyrB are important for cell activity, and can be used to construct a phylogeny [40].…”