Multiplicity and functional diversity of cyclic mononucleotide signaling in Sinorhizobium meliloti

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Discovery of the multiplicity and diversity of enzymes synthesizing and degrading the ubiquitous bacterial second messenger c-di-GMP has raised the new concept of parallel operation of highly specific second messenger-based signaling modules, which has been studied in great detail during the last decade. In contrast, multiplicity and functional diversification of cyclases synthesizing the cyclic mononucleotide second messengers cAMP and/or cGMP is poorly investigated in microbiology. Our computational analysis of genomes of symbiotic nitrogen fixing members of the alpha-proteobacterial Rhizobiaceae revealed an exceptionally high number of adenylate/guanylate cyclase (AC/GC) genes in these bacteria. Sinorhizobium meliloti strain Rm2011 harbors 28 class III AC/GC genes, ten genes encoding CRP-like proteins and seven genes encoding phosphodiesterases (PDEs) that may hydrolyze cyclic mononucleotides. According to the organization of catalytic CHD and additional non-catalytic domains the encoded AC/GC proteins can be grouped into nine subclasses. Preliminary work has demonstrated cAMP and cGMP synthesis and secretion by S. meliloti and provided an initial characterization of the activities of most of these AC/GC and CRP-like proteins. The high variety in components related to cAMP/cGMP signaling and the excellent accessibility to genetic manipulations make S. meliloti an ideal model system. Our overarching goal is to understand the role of multiplicity and functional diversification of cyclic mononucleotide signaling in S. meliloti. We propose a research plan that will explore the catalytic activities and biological roles of mononucleotide cyclases and PDEs, the sensory input to mononucleotide cyclases, and the regulatory output of cAMP/cGMP signaling in this model organism. Ultimately, our insights will allow for comparisons of the molecular principles underlying functional diversification in bacterial c-di-GMP and cAMP/cGMP signaling networks in the framework of the priority program SPP 1879.