ArticleJournal of bacteriology2021
Pyruvate Oxidase as a Key Determinant of Pneumococcal Viability during Transcytosis across Brain Endothelium.
Article in Journal of bacteriology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Article
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- The Participation of Acetyl Phosphate, a Microbial and Host Metabolite, in the Regulation of the Calcium Balance in Mitochondria and Cells.International journal of molecular sciences · 2026Article
- Stem cell-derived brain-like endothelial cells to interrogateVirulence · 2025Article
- Commensal to pathogen switch in Streptococcus pneumoniae is influenced by a thermosensing master regulator.PLoS pathogens · 2025Article
- Breaking the fortress: a mechanistic review of meningitis-causing bacteria breaching tactics in blood brain barrier.Cell communication and signaling : CCS · 2025Review
- Influence of the Microbial Metabolite Acetyl Phosphate on Mitochondrial Functions Under Conditions of Exogenous Acetylation and Alkalization.Metabolites · 2024Article
- Pneumococcal hydrogen peroxide regulates host cell kinase activity.Frontiers in immunology · 2024Article
- Impact of Endogenous Pneumococcal Hydrogen Peroxide on the Activity and Release of Pneumolysin.Toxins · 2023Article
- Anticariogenic Activity of Celastrol and Its Enhancement of Streptococcal Antagonism in Multispecies Biofilm.Antibiotics (Basel, Switzerland) · 2023Article
- The oxidative stress response ofFrontiers in microbiology · 2023Review
- Development of a Multi-Epitope Vaccine forInternational journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptococcus pneumoniae invades a myriad of host tissues following efficient breaching of cellular barriers. However, strategies adopted by pneumococcus for evasion of host intracellular defenses governing successful transcytosis across host cellular barriers remain elusive. In this study, using brain endothelium as a model host barrier, we observed that pneumococcus containing endocytic vacuoles (PCVs), formed following S. pneumoniae internalization into brain microvascular endothelial cells (BMECs), undergo early maturation and acidification, with a major subset acquiring lysosome-like characteristics. Exploration of measures that would preserve pneumococcal viability in the lethal acidic pH of these lysosome-like vacuoles revealed a critical role of the two-component system response regulator, CiaR, which was previously implicated in induction of acid tolerance response. Pyruvate oxidase (SpxB), a key sugar-metabolizing enzyme that catalyzes oxidative decarboxylation of pyruvate to acetyl phosphate, was found to contribute to acid stress tolerance, presumably via acetyl phosphate-mediated phosphorylation and activation of CiaR, independent of its cognate kinase CiaH. Hydrogen peroxide, the by-product of an SpxB-catalyzed reaction, was also found to improve pneumococcal intracellular survival by oxidative inactivation of lysosomal cysteine cathepsins, thus compromising the degradative capacity of the host lysosomes. As expected, a Δ
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