TY - JOUR
T1 - Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae
AU - Yamaguchi, Masaya
AU - Goto, Kana
AU - Hirose, Yujiro
AU - Yamaguchi, Yuka
AU - Sumitomo, Tomoko
AU - Nakata, Masanobu
AU - Nakano, Kazuhiko
AU - Kawabata, Shigetada
N1 - Funding Information:
This study was supported in part by the Japan Society for the Promotion of Science KAKENHI (grant numbers 15H05012, 16H05847, 16K15787, 17H05103, 17K11666 and 17H04369); SECOM Science and Technology Foundation; Takeda Science Foundation; GSK Japan Research Grant; Asahi Glass Foundation; Kurata Memorial Hitachi Science and Technology Foundation; and Kobayashi International Scholarship Foundation. The funders had no role in study design, data collection or analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-019-0340-7
DO - 10.1038/s42003-019-0340-7
M3 - Article
C2 - 30886906
AN - SCOPUS:85065605028
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 96
ER -
