The genetic diversity of the CbpA gene in Streptococcus pneumoniae

Abstract

Streptococcus pneumoniae (pneumococcus) is a common human pathogen responsible for morbidity and mortality worldwide. It causes mild to life-threatening, inflammatory diseases such as otitis media, pneumonia, sepsis and meningitis. The prevention and management of pneumococcal infections has been very challenging. Over time there has been increasing drug resistance of pneumococcus strains against the available antibiotics. Moreover, the pneumococcal vaccines currently available in the market do not offer broad coverage against the more than 90 serotypes currently identified. If novel treatment and preventative strategies are not adopted soon, then pneumococcal disease will continue to devastate human populations, especially in the developing countries where it causes the most damage. This study comprised of 213 fully annotated complete genome sequences of S. pneumoniae downloaded from GenBank. Amino acid and nucleic acid sequences of Choline binding protein A (CbpA) were successfully extracted from 211 genomes (99%) for study of genetic variation and identification of possible conserved, immunogenic regions eligible for novel vaccine targets. Multiple SequenCe alignment by Log-Expectation (MUSCLE) was used for alignment and the phylogenetic trees and heat maps created by PhyML and R respectively. The CbpA locus was found to be highly polymorphic at both the nucleic acid and amino acid sequences. However, RaptorX server showed that 83.3% of the pneumococcal protein domains predicted were the conserved modular teichoic acid phosphorylcholine esterase Pce (2bib:A) and the CbpA R2 domain (1w9r:A). Using Transmembrane Hidden Markov Model (TMHMM) server and VaxiJen v 2.0 server, these conserved domains were shown to be extracellularly located and immunogenic. The high variability observed in CbpA suggests its importance as a natural target for host defense and essential element for the colonization of different niches within the host. Further evaluation of 2bib:A and 1w9r:A conserved regions would be required to design novel, efficacious, serotype- independent CbpA- fusion protein vaccine candidate.