title: Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation.
abstract: The Gram-positive model organism Bacillus subtilis produces the essential second messenger signaling nucleotide cyclic di-AMP. In B. subtilis and other bacteria, c-di-AMP has been implicated in diverse functions such as control of metabolism, cell division and cell wall synthesis, and potassium transport. To enhance our understanding of the multiple functions of this second messenger, we have studied the consequences of c-di-AMP accumulation at a global level by a transcriptome analysis. C-di-AMP accumulation affected the expression of about 700 genes, among them the two major operons required for biofilm formation. The expression of both operons was severely reduced both in the laboratory and a non-domesticated strain upon accumulation of c-di-AMP. In excellent agreement, the corresponding strain was unable to form complex colonies. In B. subtilis, the transcription factor SinR controls the expression of biofilm genes by binding to their promoter regions resulting in transcription repression. Inactivation of the sinR gene restored biofilm formation even at high intracellular c-di-AMP concentrations suggesting that the second messenger acts upstream of SinR in the signal transduction pathway. As c-di-AMP accumulation did not affect the intracellular levels of SinR, we conclude that the nucleotide affects the activity of SinR.
authors.affiliation: Department of General Microbiology, Institute for Microbiology and Genetics, Georg-August-University Göttingen Göttingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Gundlach
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald Greifswald, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Rath
authors.affiliation: Department of General Microbiology, Institute for Microbiology and Genetics, Georg-August-University Göttingen Göttingen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Herzberg
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald Greifswald, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mäder
authors.affiliation: Department of General Microbiology, Institute for Microbiology and Genetics, Georg-August-University Göttingen Göttingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Stülke
keywords: Bacillus subtilis; SinR; biofilm formation; c-di-AMP; phosphodiesterase