Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08

MSphere
Alejandro Gómez-MejiaSven Hammerschmidt

Abstract

Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and real-time PCR demonstrated a regulatory effect of TCS08 on genes involved mainly in environmental information processing, intermediary metabolism, and colonization by S. pneumoniae D39 and TIGR4. Striking examples are genes for fatty acid biosynthesis, genes of the arginine deiminase system, and the psa operon encoding the manganese ABC transport system. In silico analysis confirmed that TCS08 is homologous to Staphylococcus aureus SaeRS, and a SaeR-like binding motif is displayed in the promoter region of pavB, the upstream gene of the tcs08 operon encoding a surface-exposed adhesin. Indeed, PavB is regulated by TCS08 as confirmed by immunoblotting and surface abundance assays. Similarly, pilus-1 of TIGR4 is regulated by TCS08. Finally, in vivo infections using the acute pneumonia and sepsis models showed a strain-dependent effect. Loss of function of HK08 or TCS08 attenuated D39 virulence in lung infections. The RR08 deficiency attenuated T...Continue Reading

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Citations

Jul 18, 2020·Metallomics : Integrated Biometal Science·Lindsey R BurchamJustin A Thornton
Nov 27, 2020·Journal of Molecular Biology·Mohammed R AbdullahSven Hammerschmidt
Feb 27, 2021·Frontiers in Microbiology·Stefan Ness, Markus Hilleringmann
Mar 7, 2021·Microorganisms·Stephanie HirschmannSven Hammerschmidt
Aug 29, 2021·Journal of Biomedical Science·Yi-Yin ChenYu-Chia Hsieh
Sep 22, 2021·MBio·Dhriti SinhaNicholas R De Lay

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Datasets Mentioned

BETA
GSE108874

Methods Mentioned

BETA
phosphotransferase
PCR
flow cytometry
bronchoalveolar lavage
lavages
lavage
Feature Extraction
electrophoresis
FCS
bronchoalveolar lavages

Software Mentioned

Feature Extraction
Image Studio
BacMap
CellQuestPro
GeneSpring
Clustal Omega
IVIS Spectrum
Bacterial Map
StepOne
SMART ( Simpler Modular Architecture Research Tool

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