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mSphere. 2018 May 16;3(3). pii: e00165-18. doi: 10.1128/mSphere.00165-18. eCollection 2018 May-Jun.

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

Author information

1
Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany.
2
Genetics, Regeneration and Cancer (GRC) Research Group, University Research Center (SIU), Universidad de Antioquia (UdeA), Medellin, Colombia.
3
Basic and Applied Microbiology (MICROBA) Research Group, School of Microbiology, Universidad de Antioquia (UdeA), Medellin, Colombia.
4
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany.
5
Department of Microbiology, University of Kaiserslautern, Kaiserslautern, Germany.
6
Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany sven.hammerschmidt@uni-greifswald.de.

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 TIGR4 in pneumonia, while there was no effect on sepsis. In contrast, lack of HK08 procured a highly virulent TIGR4 phenotype in both pneumonia and sepsis infections. Taken together, these data indicate the importance of TCS08 in pneumococcal fitness to adapt to the milieu of the respiratory tract during colonization.IMPORTANCEStreptococcus pneumoniae interplays with its environment by using 13 two-component regulatory systems and one orphan response regulator. These systems are involved in the sensing of environmental signals, thereby modulating pneumococcal pathophysiology. This study aimed to understand the functional role of genes subject to control by the TCS08. The identified genes play a role in transport of compounds such as sugars or amino acids. In addition, the intermediary metabolism and colonization factors are modulated by TCS08. Thus, TCS08 regulates genes involved in maintaining pneumococcal physiology, transport capacity, and adhesive factors to enable optimal colonization, which represents a prerequisite for invasive pneumococcal disease.

KEYWORDS:

Streptococcus pneumoniae; colonization; gene regulation; physiology; two-component regulatory systems

PMID:
29769380
PMCID:
PMC5956151
DOI:
10.1128/mSphere.00165-18
[Indexed for MEDLINE]
Free PMC Article

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