Hirschmann, S. | Search bioRxiv

bioRxiv2025

PneumoWiki: A pan-genome-based database for the pathogen Streptococcus pneumoniae

The Gram-positive bacterium Streptococcus pneumoniae is a major human pathogen that exhibits more than 100 different capsular serotypes and considerable genomic variation. S. pneumoniae is also an important model organism for basic and biomedical research, with a number of strains with different characteristics being used. To address this, we have created the manually curated pan-genome database PneumoWiki (https://pneumowiki.med.uni-greifswald.de) that integrates genomic data from 43 S. pneumoniae strains with various aspects of functional annotation. All data relating to a specific gene and gene product are compiled on a Gene page. In addition to the gene and protein sequences and annotation from NCBI RefSeq, the Gene pages contain data on, for example, gene essentiality, protein function and localization, and transcriptional regulation. The information is supplemented with links to the data sources as well as to other databases and relevant literature. The basic concept of PneumoWiki is the interlinked presentation of pan-genome-based and strain-specific information. Therefore, register tabs with strain names at the top of the Gene pages allow switching between orthologous genes and the corresponding pan-genome page. The pan-genome gene pages contain a summary with functional information and the occurrence of the gene, an orthologue table for the 43 S. pneumoniae strains, a multiple-strain genome viewer as well as a protein sequence alignment. PneumoWiki was developed as a user-friendly tool and is available free of charge. The data collected in PneumoWiki are accessible via various download options to support bioinformatic applications. Overall, PneumoWiki is a resource for the pneumococcal research community that supports the analysis and interpretation of research data and, in particular, enables the integration of the knowledge available for different S. pneumoniae strains.

microbiology↗

bioRxiv2018

Pneumococcal metabolic adaptation and colonization is regulated by the two-component regulatory system 08

Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of the TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and real-time PCR demonstrated a regulatory effect of the TCS08 on genes involved mainly in environmental information processing, intermediary metabolism, and colonization by S. pneumoniae D39 and TIGR4. Striking examples are genes of the fatty acid biosynthesis, arginine-deiminase system, and 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 promotor region of pavB, the upstream gene of the tcs08 operon encoding a surface-exposed adhesin. Indeed, PavB is regulated by the 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.\n\nIMPORTANCEStreptococcus 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.

microbiology↗