Streptococcus pneumoniae Evades Host Cell Phagocytosis and Limits Host Mortality Through Its Cell Wall Anchoring Protein PfbA.

Masaya Yamaguchi,Masayuki Ono,Yujiro Hirose,Yutaka Terao,Shigetada Kawabata,Moe Takemura,Masanobu Nakata,Tomoko Sumitomo

doi:10.3389/fcimb.2019.00301

Masaya Yamaguchi, Masayuki Ono + Show 6 more

Open Access

https://doi.org/10.3389/fcimb.2019.00301

Copy DOI

Abstract

Streptococcus pneumoniae is a Gram-positive bacterium belonging to the oral streptococcus species, mitis group. This pathogen is a leading cause of community-acquired pneumonia, which often evades host immunity and causes systemic diseases, such as sepsis and meningitis. Previously, we reported that PfbA is a β-helical cell surface protein contributing to pneumococcal adhesion to and invasion of human epithelial cells in addition to its survival in blood. In the present study, we investigated the role of PfbA in pneumococcal pathogenesis. Phylogenetic analysis indicated that the pfbA gene is highly conserved in S. pneumoniae and Streptococcus pseudopneumoniae within the mitis group. Our in vitro assays showed that PfbA inhibits neutrophil phagocytosis, leading to pneumococcal survival. We found that PfbA activates NF-κB through TLR2, but not TLR4. In addition, TLR2/4 inhibitor peptide treatment of neutrophils enhanced the survival of the S. pneumoniae ΔpfbA strain as compared to a control peptide treatment, whereas the treatment did not affect survival of a wild-type strain. In a mouse pneumonia model, the host mortality and level of TNF-α in bronchoalveolar lavage fluid were comparable between wild-type and ΔpfbA-infected mice, while deletion of pfbA decreased the bacterial burden in bronchoalveolar lavage fluid. In a mouse sepsis model, the ΔpfbA strain demonstrated significantly increased host mortality and TNF-α levels in plasma, but showed reduced bacterial burden in lung and liver. These results indicate that PfbA may contribute to the success of S. pneumoniae species by inhibiting host cell phagocytosis, excess inflammation, and mortality by interacting with TLR2.

Highlights

Streptococcus pneumoniae is a Gram-positive bacterium belonging to the mitis group that colonizes the human nasopharynx in ∼20% of children without causing clinical symptoms (Kawamura et al, 1995; Bogaert et al, 2004; Richards et al, 2014)
The tBLASTn search of the NCBI Nucleotide collection database showed that pfbA-homologs were present only in S. pneumoniae, S. pseudopneumoniae, S. gordonii, and Streptococcus merionis
The pfbA gene homologs were identified in mitis group Streptococcus (S. pneumoniae, S. pseudopneumoniae, S. mitis, S. oralis, S. infantis, S. gordonii, and S. anginosus), Sphingomonas paucimobilis, Haemophilus haemolyticus, Granulicatella species, and S. merionis

Summary

Introduction

Streptococcus pneumoniae is a Gram-positive bacterium belonging to the mitis group that colonizes the human nasopharynx in ∼20% of children without causing clinical symptoms (Kawamura et al, 1995; Bogaert et al, 2004; Richards et al, 2014). S. pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis worldwide. Following the introduction of pneumococcal conjugate vaccines, S. pneumoniae is still responsible for two thirds of all cases of meningitis (McIntyre et al, 2012). Centers for Disease Control and Prevention data from active bacterial core surveillance for 2009 to 2013 indicated that pneumococcal conjugate vaccines work as a useful tool against antibiotic resistance (Kim et al, 2016). These vaccines generate selective pressure, and non-vaccine serotypes of S. pneumoniae are increasing worldwide (Flasche et al, 2011; Golubchik et al, 2012)

Methods

Results

Conclusion