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Increased Intracellular Cyclic di-AMP Levels Sensitize Streptococcus gallolyticus subsp. gallolyticus to Osmotic Stress and Reduce Biofilm Formation and Adherence on Intestinal Cells.

ABSTRACT: Cyclic di-AMP is a recently identified second messenger exploited by a number of Gram-positive bacteria to regulate important biological processes. Here, we studied the phenotypic alterations induced by the increased intracellular c-di-AMP levels in Streptococcus gallolyticus, an opportunistic pathogen responsible for septicemia and endocarditis in the elderly. We report that an S. gallolyticus c-di-AMP phosphodiesterase gdpP knockout mutant, which displays a 1.5-fold higher intracellular c-di-AMP levels than the parental strain UCN34, is more sensitive to osmotic stress and is morphologically smaller than the parental strain. Unexpectedly, we found that a higher level of c-di-AMP reduced biofilm formation of S. gallolyticus on abiotic surfaces and reduced adherence and cell aggregation on human intestinal cells. A genome-wide transcriptomic analysis indicated that c-di-AMP regulates many biological processes in S. gallolyticus, including the expression of various ABC transporters and disease-associated genes encoding bacteriocin and Pil3 pilus. Complementation of the gdpP in-frame deletion mutant with a plasmid carrying gdpP in trans from its native promoter restored bacterial morphology, tolerance to osmotic stress, biofilm formation, adherence to intestinal cells, bacteriocin production, and Pil3 pilus expression. Our results indicate that c-di-AMP is a pleiotropic signaling molecule in S. gallolyticus that may be important for S. gallolyticus pathogenesis.IMPORTANCE Streptococcus gallolyticus is an opportunistic pathogen responsible for septicemia and endocarditis in the elderly and is also strongly associated with colorectal cancer. S. gallolyticus can form biofilms, express specific pili to colonize the host tissues, and produce a specific bacteriocin allowing killing of commensal bacteria in the murine colon. Nevertheless, how the expression of these colonization factors is regulated remains largely unknown. Here, we show that c-di-AMP plays pleiotropic roles in S. gallolyticus, controlling the tolerance to osmotic stress, cell size, biofilm formation on abiotic surfaces, adherence and cell aggregation on human intestinal cells, expression of Pil3 pilus, and production of bacteriocin. This study indicates that c-di-AMP may constitute a key regulatory molecule for S. gallolyticus host colonization and pathogenesis.

SUBMITTER: Teh WK

PROVIDER: S-EPMC6398277 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Increased Intracellular Cyclic di-AMP Levels Sensitize Streptococcus gallolyticus subsp. gallolyticus to Osmotic Stress and Reduce Biofilm Formation and Adherence on Intestinal Cells.

Teh Wooi Keong WK Dramsi Shaynoor S Tolker-Nielsen Tim T Yang Liang L Yang Liang L Givskov Michael M

Journal of bacteriology 20190225 6

Cyclic di-AMP is a recently identified second messenger exploited by a number of Gram-positive bacteria to regulate important biological processes. Here, we studied the phenotypic alterations induced by the increased intracellular c-di-AMP levels in Streptococcus gallolyticus, an opportunistic pathogen responsible for septicemia and endocarditis in the elderly. We report that an S. gallolyticus c-di-AMP phosphodiesterase gdpP knockout mutant, which displays a 1.5-fold higher ...[more]

PMID: 30617242

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Project description:Streptococcus gallolyticus subsp. gallolyticus is a commensal bacterium of the human gastrointestinal tract, and a pathogen causing infective endocarditis and other biofilm-associated infections via exposed collagen. This study focuses on the characterization of the biofilm formation and collagen adhesion of S. gallolyticus subsp. gallolyticus under different conditions. In this study, it has been observed that the isolate UCN 34 is resistant to 20 mg/ml lysozyme in BHI medium, whereas the strain BAA-2069 builds more biofilm in the presence of lysozyme compared to in a control of BHI without lysozyme. A transcriptome analysis with whole genome microarrays of these two isolates in BHI medium with lysozyme compared to control without lysozyme revealed changes in gene expression levels. In the isolate BAA-2069, 67 genes showed increased expression in the presence of lysozyme, while in the isolate UCN 34, 165 genes showed increased expression and 30 genes showed decreased expression through lysozyme treatment. Products of genes which were higher expressed are in involved in transcription and translation, in cell-wall modification, in hydrogen peroxide resistance and in bacterial immunity. Furthermore, the adhesion ability of different strains of S. gallolyticus subsp. gallolyticus to collagen type I and IV was analyzed. Thereby, we compared the adhesion of 46 human isolates with 23 isolates from animals. It was shown that the adhesion ability depends significantly on whether the isolate was isolated from human or animal. For example, high adhesion ability was observed for strain UCN 34 isolated from an infective endocarditis patient, whereas strain DSM 16831 isolated from koala feces adhered only marginally to collagen. Full genome microarray analysis of these two strains revealed strain-dependent gene expression due to adhesion. The expression of 25 genes of a transposon and 15 genes of a phage region in strain DSM 16831 were increased, which corresponds to horizontal gene transfer. Adherence to collagen in strain UCN 34 led to higher expression of 27 genes and lower expression of 31 genes. This was suggestive of a change in nutrient uptake.

Dataset Information

Increased Intracellular Cyclic di-AMP Levels Sensitize Streptococcus gallolyticus subsp. gallolyticus to Osmotic Stress and Reduce Biofilm Formation and Adherence on Intestinal Cells.

Publications

Increased Intracellular Cyclic di-AMP Levels Sensitize Streptococcus gallolyticus subsp. gallolyticus to Osmotic Stress and Reduce Biofilm Formation and Adherence on Intestinal Cells.

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