Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
Alejandro Gómez-Mejia,
Gustavo Gámez,
Stephanie Hirschmann,
Viktor Kluger,
Hermann Rath,
Sebastian Böhm,
Franziska Voss,
Niamatullah Kakar,
Lothar Petruschka,
Uwe Völker,
Reinhold Brückner,
Ulrike Mäder,
Sven Hammerschmidt
Affiliations
Alejandro Gómez-Mejia
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
Gustavo Gámez
Genetics, Regeneration and Cancer (GRC) Research Group, University Research Center (SIU), Universidad de Antioquia (UdeA), Medellin, Colombia
Stephanie Hirschmann
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
Viktor Kluger
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
Hermann Rath
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany
Sebastian Böhm
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
Franziska Voss
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
Niamatullah Kakar
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
Lothar Petruschka
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
Uwe Völker
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany
Reinhold Brückner
Department of Microbiology, University of Kaiserslautern, Kaiserslautern, Germany
Ulrike Mäder
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University Medicine Greifswald, Greifswald, Germany
Sven Hammerschmidt
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
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. IMPORTANCE Streptococcus 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.
