Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/85354
Title: Increased intracellular cyclic di-AMP levels sensitize Streptococcus gallolyticus subsp. gallolyticus to osmotic stress and reduce biofilm formation and adherence on intestinal cells
Authors: Teh, Wooi Keong
Dramsi, Shaynoor
Tolker-Nielsen, Tim
Yang, Liang
Givskov, Michael
Keywords: C-di-AMP
DRNTU::Science::Biological sciences
Streptococcus gallolyticus
Issue Date: 2019
Source: Teh, W. K., Dramsi, S., Tolker-Nielsen, T., Yang, L., & Givskov, M. (2019). Increased intracellular cyclic di-AMP levels sensitize Streptococcus gallolyticus subsp. gallolyticus to osmotic stress and reduce biofilm formation and adherence on intestinal cells. Journal of Bacteriology, 201(6), e00597-18-. doi:10.1128/JB.00597-18.
Series/Report no.: Journal of Bacteriology
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.
URI: https://hdl.handle.net/10356/85354
http://hdl.handle.net/10220/48383
ISSN: 0021-9193
DOI: 10.1128/JB.00597-18
Rights: © 2019 Teh et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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