Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

ABSTRACT

This study assessed the role of high mobility group box 1 (HMGB1) in pneumococcal pneumonia. Intratracheal challenge of mice with Streptococcus pneumoniae significantly increased HMGB1 levels in bronchoalveolar lavage fluid. Immunostaining of lung sections revealed HMGB1 localization in both alveolar epithelial and infiltrating polymorphonuclear cells in S. pneumoniae ‐infected mice. In vitro, pneumolysin, a pore‐forming pneumococcal toxin, causes HMGB1 release from neutrophils. Additionally, recombinant HMGB1 enhanced TNF‐α production in RAW264.7 macrophages, human neutrophils, and THP‐1 cells. These findings indicate that neutrophil‐derived HMGB1 serves as a pro‐inflammatory mediator and exacerbates of lung inflammation during pneumococcal infection.

DOI： 10.1111/1348-0421.70054

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1348-0421.70054

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

ABSTRACT

To investigate the mechanisms underlying pneumococcal infection, a proteomic analysis was previously conducted to identify pneumococcal proteins in infected mouse samples. In the present study, we characterized three proteins, ATP synthase subunit beta (AtpD), ABC transporter transmembrane protein (Vex3), and fructose bisphosphate aldolase (Fba), which bind to human plasminogen and subsequently facilitate its conversion to plasmin by tissue‐type plasminogen activator. These findings suggest that Streptococcus pneumoniae might exploit the proteolytic activity of plasmin to promote infection and highlights the potential importance of plasminogen‐binding capacity in the pathogenesis of pneumococcal infection.

DOI： 10.1111/1348-0421.70000

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Streptococcus pneumoniae causes otitis media, sinusitis, and serious diseases such as pneumonia and bacteremia. However, the in vivo dynamics of S. pneumoniae infections and disease severity are not fully understood. In this study, we investigated pneumococcal proteins detected in the bronchoalveolar lavage fluid of an S. pneumoniae-infected mouse, which were assumed to be expressed during infection. Analysis of three proteins with unknown infection-related functions revealed that recombinant Fe-S cluster assembly ATP-binding protein (SufC) binds to the host plasminogen and promotes its conversion into plasmin. SufC was detected in the bacterial cell-surface protein fraction, but it had no extracellular secretory signal. This study suggests that S. pneumoniae releases SufC extracellularly through LytA-dependent autolysis, binding to the bacterial cell surface and host plasminogen and promoting its conversion into plasmin. The recruitment of plasmin by S. pneumoniae is considered useful for bacterial survival and spread, and SufC is suggested to facilitate this process.

DOI： 10.3390/microorganisms11122969

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The main causative agent of pneumonia, Streptococcus pneumoniae, is also responsible for invasive diseases. S. pneumoniae recruits human plasminogen for the invasion and colonization of host tissues. We previously discovered that S. pneumoniae triosephosphate isomerase (TpiA), an enzyme involved in intracellular metabolism that is essential for survival, is released extracellularly to bind human plasminogen and facilitate its activation. Epsilon-aminocaproic acid, a lysine analogue, inhibits this binding, suggesting that the lysine residues in TpiA are involved in plasminogen binding. In this study, we generated site-directed mutant recombinants in which the lysine residue in TpiA was replaced with alanine and analyzed their binding activities to human plasminogen. Results from blot analysis, enzyme-linked immunosorbent assay, and surface plasmon resonance assay revealed that the lysine residue at the C-terminus of TpiA is primarily involved in binding to human plasminogen. Furthermore, we found that TpiA binding to plasminogen through its C-terminal lysine residue was required for the promotion of plasmin activation by activating factors.

DOI： 10.3390/microorganisms11051198

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Two plasminogen binding proteins were identified from a mouse infected with Streptococcus pneumoniae. The pneumococcal proteins were annotated as ATP‐dependent Clp protease ATP‐binding subunit (ClpC) and excinuclease ABC subunit C (UvrC) using the isobaric tags for relative and absolute quantification (iTRAQ) method. Recombinants of both proteins showed significant binding to plasminogen and were found to promote plasminogen activation by tissue‐type plasminogen activator. In addition, ClpC and UvrC were LytA‐dependently released into the culture supernatant and bound to the bacterial surface. These results suggest that S. pneumoniae releases ClpC and UvrC by autolysis and recruits them to the bacterial surface, where they bind to plasminogen and promote its activation, contributing to extracellular matrix degradation and tissue invasion.

DOI： 10.1111/1348-0421.13040

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1348-0421.13040

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Event date： 2025.9

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2025.5

Presentation type：Poster presentation  

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Event date： 2024.8

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2023.9

Presentation type：Poster presentation  

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