Phylogenetic Analysis of Antigenic Variability in Klebsiella pneumoniae against Antibacterial Ocular Drugs

Abstract

Klebsiella pneumonia, associated with significant proportion of hospital-acquired urinary tract infections, pneumonia, soft tissue infections, liver abscess, endophthalmitis and meningitis. Though the antibiotic eye drops against K. pneumoniae are available, immunologically distinct strains evolved by mutations in epitopes and leads resistance to ocular antibacterial drugs. The analysis of escape mutation necessitates new drug development.Also, it constitutes a major challenge to effective drug design.  In present work, molecular basis of antigenic resistance in K. pneumoniae against the antibacterial ocular drugs was investigated. The resistance genes were identified and identified that genetic drift was found in 16 genes and higher number of mutaionswas found in class-A beta-lactamase.The protein sequences of class-A beta-lactamase from resistance strains were obtained and antigenic variability was carried out in terms of antigenic distance based on the sequence alignment and phylogenetic analysis. Moreover the docking study of protein with drug molecules was done in order to find out whether the mutations are at active site or at other residues.It was found that, mutations were dispersed throughout the sequence, and were not found at a particular segment. The escape mutation was found less at active site than rest. It concludes that the mutations in non-active residues may leads to changes in electrostatic and steric interactions. In this work, drift was analyzed in class-A beta-lactamase alone, the overall analysis may play potential role in effective designing of antibacterial drug against K. pneumoniae.

Keywords: Antigenic variability, Class-A beta-lactamase, Klebsiella pneumonia, ocular drugs, phylogeny