Project description:Background: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is a pathogen of infective endocarditis. It was observed previously that this bacterium survives longer in macrophages than other species and the phagocytic uptake by and survival in THP-1 macrophages is strain-dependent. Methods: The phagocytosis assay was performed with THP-1 macrophages. S. gallolyticus specific whole genome microarrays were used for transcriptome analysis. Results: Better survival in macrophages was observed for UCN34, BAA-2069 and ATCC43143 than for DSM16831 and LMG17956. S. gallolyticus strains show high resistance to tested bactericidal agents (acid, lysozyme and hydrogen peroxide). S. gallolyticus stimulates significant lower cytokine gene expression and causes less lysis of macrophages compared to the control strain S. aureus. S. gallolyticus reacts to oxidative burst with a higher gene expression of NADH oxidase initially at the early phase. Expression of genes involved in D-alanylation of teichoic acid, carbohydrate metabolism and transport systems were upregulated thereafter. Conclusion: S. gallolyticus is very resistant to bactericidal agents normally causing degradation of bacteria in phagolysosomes. Additionally, the D-alanylation of teichoic acid is an important factor for survival.
Project description:Background: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is a pathogen of infective endocarditis. It was observed previously that this bacterium survives longer in macrophages than other species and the phagocytic uptake by and survival in THP-1 macrophages is strain-dependent. Methods: The phagocytosis assay was performed with THP-1 macrophages. S. gallolyticus specific whole genome microarrays were used for transcriptome analysis. Results: Better survival in macrophages was observed for UCN34, BAA-2069 and ATCC43143 than for DSM16831 and LMG17956. S. gallolyticus strains show high resistance to tested bactericidal agents (acid, lysozyme and hydrogen peroxide). S. gallolyticus stimulates significant lower cytokine gene expression and causes less lysis of macrophages compared to the control strain S. aureus. S. gallolyticus reacts to oxidative burst with a higher gene expression of NADH oxidase initially at the early phase. Expression of genes involved in D-alanylation of teichoic acid, carbohydrate metabolism and transport systems were upregulated thereafter. Conclusion: S. gallolyticus is very resistant to bactericidal agents normally causing degradation of bacteria in phagolysosomes. Additionally, the D-alanylation of teichoic acid is an important factor for survival.
Project description:Background: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is a pathogen of infective endocarditis. It was observed previously that this bacterium survives longer in macrophages than other species and the phagocytic uptake by and survival in THP-1 macrophages is strain-dependent. Methods: The phagocytosis assay was performed with THP-1 macrophages. S. gallolyticus specific whole genome microarrays were used for transcriptome analysis. Results: Better survival in macrophages was observed for UCN34, BAA-2069 and ATCC43143 than for DSM16831 and LMG17956. S. gallolyticus strains show high resistance to tested bactericidal agents (acid, lysozyme and hydrogen peroxide). S. gallolyticus stimulates significant lower cytokine gene expression and causes less lysis of macrophages compared to the control strain S. aureus. S. gallolyticus reacts to oxidative burst with a higher gene expression of NADH oxidase initially at the early phase. Expression of genes involved in D-alanylation of teichoic acid, carbohydrate metabolism and transport systems were upregulated thereafter. Conclusion: S. gallolyticus is very resistant to bactericidal agents normally causing degradation of bacteria in phagolysosomes. Additionally, the D-alanylation of teichoic acid is an important factor for survival.
Project description:Background: Streptococcus gallolyticus subsp. gallolyticus (S. gallolyticus) is a pathogen of infective endocarditis. It was observed previously that this bacterium survives longer in macrophages than other species and the phagocytic uptake by and survival in THP-1 macrophages is strain-dependent. Methods: The phagocytosis assay was performed with THP-1 macrophages. S. gallolyticus specific whole genome microarrays were used for transcriptome analysis. Results: Better survival in macrophages was observed for UCN34, BAA-2069 and ATCC43143 than for DSM16831 and LMG17956. S. gallolyticus strains show high resistance to tested bactericidal agents (acid, lysozyme and hydrogen peroxide). S. gallolyticus stimulates significant lower cytokine gene expression and causes less lysis of macrophages compared to the control strain S. aureus. S. gallolyticus reacts to oxidative burst with a higher gene expression of NADH oxidase initially at the early phase. Expression of genes involved in D-alanylation of teichoic acid, carbohydrate metabolism and transport systems were upregulated thereafter. Conclusion: S. gallolyticus is very resistant to bactericidal agents normally causing degradation of bacteria in phagolysosomes. Additionally, the D-alanylation of teichoic acid is an important factor for survival.
Project description:The opportunistic pathogen Streptococcus gallolyticus is one of the few intestinal bacteria that has been consistently linked to colorectal cancer (CRC). This study aimed to identify S. gallolyticus-induced pathways that could on the long-term add to CRC progression. Transcription profiling of S. gallolyticus-exposed CRC-cells revealed the persistent induction of enzymes involved in biotransformation pathways. Specifically, a diffusible factor of S. gallolyticus (SGF-X) interacts with the aryl hydrocarbon receptor thereby inducing CYP1 enzymes that catalyze the bioactivation of polycyclic aromatic hydrocarbons (PAHs) into toxic intermediates. Importantly, priming CRC-cells with SGF-X containing medium increased the DNA damaging effect of the PAH 3-methylcholanthrene, which was not observed for other intestinal bacteria. In conclusion, this study shows for the first time that bacteria can modulate the biotransformation capacity of CRC-cells that offers a novel theory for a contributing role of S. gallolyticus in the etiology of sporadic CRC. Key words : Colorectal cancer cells, Streptococcus bovis, streptococcus gallolyticus, host-pathogen interactions, Cytochrome P4501A1, DNA-damage, polycyclic aromatic hydrocarbons
Project description:Streptococcus gallolyticus sp. gallolyticus (SGG) is a gut pathobiont involved in the development of colorectal cancer (CRC). To decipher SGG contribution in tumor initiation and/or acceleration respectively, a global transcriptome was performed in normal colonic cells (FHC) and in tumoral colonic cells (HT29). To identify SGG-specific alterations, we chose the phylogenetically closest relative, Streptococcus gallolyticus subsp. macedonicus (SGM) as control bacterium. We show that SGM, a bacterium generally considered as safe, did not induce any transcriptional changes on the two human colonic cells FHC and HT29. The transcriptional reprogramming induced by SGG in FHC and HT29 cells was significantly different, however most of the genes up- and down-regulated were associated with cancer disease. Top up-regulated genes related to cancer were: (i) IL-20, CLK1, SORBS2, ERG1, PIM1, SNORD3A for normal FHC cells and (ii) TSLP, BHLHA15, LAMP3, ZNF27B, KRT17, ATF3 for cancerous HT29 cells. SGG induces much stronger transcriptional changes in cancerous than in normal colonic cells (2090 vs genes 128). Gene set enrichment analysis reveals that SGG-induced strong ER- (endoplasmic reticulum) stress and UPR- (unfolded protein response) activation in colonic epithelial cells. Our results suggest that SGG induces a pro-tumoral shift in human colonic cells particularly in transformed cells potentially accelerating tumor development in the colon.
Project description:Streptococcus gallolyticus subsp. gallolyticus is a commensal of the human gastrointestinal tract and a pathogen of infective endocarditis and other biofilm-associated infections with exposed collagen. Therefore, this study focuses on the characterization of the biofilm formation and collagen adhesion of S. gallolyticus subsp. gallolyticus under different conditions. It has been observed that lysozyme triggers biofilm formation divergently in the analyzed S. gallolyticus subsp. gallolyticus strains. The transcriptome analysis was performed for two strains which form more biofilm in the presence of lysozyme. Lysozyme leads to higher expression of genes of transcription and translation, of the dlt operon (cell wall modification), of hydrogen peroxide resistance proteins and of two immunity proteins which could be involved in biofilm formation. Furthermore, the adhesion ability of 73 different S. gallolyticus subsp. gallolyticus strains to collagen type I and IV was analyzed. High adhesion ability was observed for the strain UCN 34, whereas the strain DSM 16831 adhered only marginally to collagen. The full genome microarray analysis revealed strain-dependent gene expression due to adhesion. The expression of genes of a transposon and a phage region in strain DSM 16831 were increased, which corresponds to lateral gene transfer. Adherence to collagen leads to a change in the expression of genes of nutrients uptake in the strain UCN 34.