Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae.
Masaya YamaguchiKana GotoYujiro HiroseYuka YamaguchiTomoko SumitomoMasanobu NakataKazuhiko NakanoShigetada KawabataPublished in: Communications biology (2019)
Evolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins since Streptococcus pneumoniae is one of the pathogens posing the greatest threats to human health. Phylogenetic and molecular analyses revealed that cbpJ had the highest codon rates to total numbers of codons under considerable negative selection among those examined. Our in vitro and in vivo assays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency of cbpL under relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.
Keyphrases
- antimicrobial resistance
- pseudomonas aeruginosa
- escherichia coli
- staphylococcus aureus
- biofilm formation
- human health
- cell surface
- risk assessment
- genome wide
- transcription factor
- climate change
- cystic fibrosis
- immune response
- intensive care unit
- gene expression
- dendritic cells
- molecular dynamics simulations
- molecular dynamics
- density functional theory
- high resolution
- single molecule
- gram negative
- bioinformatics analysis
- mass spectrometry