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 Keong1,2; Dramsi, Shaynoor3,6; Tolker-Nielsen, Tim4; Yang, Liang1,5,7; Givskov, Michael1,4

2019-03

10.1128/JB.00597-18

JOURNAL OF BACTERIOLOGY   影响因子和分区

0021-9193

1098-5530

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.

Streptococcus gallolyticus c-di-AMP Streptococcus bovis biofilm cell adherence

SCI

英语

通讯

Ministry of Education Singapore under its Research Centre of Excellence Program (SCELSE), AcRF Tier 2 from the Ministry of Education, Singapore[MOE2016-T2-1-010]

Microbiology

Microbiology

WOS:000459547300004

AMER SOC MICROBIOLOGY

MICROBIOLOGY

Web of Science

1.Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn, Singapore, Singapore
2.Nanyang Technol Univ, Interdisciplinary Grad Sch, Singapore, Singapore
3.Inst Pasteur, Unite Biol Bacteries Pathogenes Gram Positif, Paris, France
4.Univ Copenhagen, Costerton Biofilm Ctr, Dept Immunol & Microbiol, Copenhagen, Denmark
5.Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore
6.CNRS, ERL6002, Paris, France
7.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China

Teh, Wooi Keong,Dramsi, Shaynoor,Tolker-Nielsen, Tim,et al. Increased Intracellular Cyclic di-AMP Levels Sensitize Streptococcus gallolyticus subsp. gallolyticus to Osmotic Stress and Reduce Biofilm Formation and Adherence on Intestinal Cells[J]. JOURNAL OF BACTERIOLOGY,2019,201(6).

Teh, Wooi Keong,Dramsi, Shaynoor,Tolker-Nielsen, Tim,Yang, Liang,&Givskov, Michael.(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).

Teh, Wooi Keong,et al."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(2019).