Cyclic di-GMP Signaling in Salmonella enterica serovar Typhimurium

Abstract

Cyclic di-GMP is perhaps the most abundant nucleotide-based second messenger in bacteria. In the gamma-proteobacterium Salmonella enterica serovar Typhimurium, a gastrointestinal pathogen, this signaling network regulates biofilm formation, flagella-associated physiology, and acute virulence properties. This chapter summarizes the impact of the complex cyclic di-GMP signaling network on the physiology of S. typhimurium in different environments and compares its consequences, when appropriate, with the close relative, the commensal and pathogenic Escherichia coli. The substantial diversity and variability in the cyclic di-GMP turnover protein network span from single amino acid replacements and stop codon variants in individual proteins to deletion and acquisition of novel cyclic di-GMP turnover genes by horizontal transfer. Despite differences in enzyme activities and gene combinations, cyclic di-GMP signaling modules become integrated into a common but even isolate-specific regulation of lifestyle transitions that are coordinated with cell cycle regulation. On a wider phylogenetic perspective, the observed conservation of cyclic di-GMP turnover proteins with a similar domain structure found in S. enterica throughout the phylogenetic tree poses a quest for the origin and maintenance of common principles in cyclic di-GMP signaling.