The ubiquitous cyclic di-GMP (c-di-GMP) network is highly redundant with numerous GGDEF domain proteins as diguanylate cyclases and EAL domain proteins as c-di-GMP specific phosphodiesterases comprising those domains as two of the most abundant bacterial domain superfamilies. One hallmark of the c-di-GMP network is its exalted plasticity as c-di-GMP turnover proteins can rapidly vanish from species within a genus and possess an above average transmissibility. To address the evolutionary forces of c-di-GMP turnover protein maintenance, conservation, and diversity, we investigated a Gram-positive and a Gram-negative species, which preserved only one single clearly identifiable GGDEF domain protein. Species of the family Morganellaceae of the order Enterobacterales exceptionally show disappearance of the c-di-GMP signaling network, but Proteus spp. still retained one diguanylate cyclase. As another example, in species of the bovis, pyogenes, and salivarius subgroups as well as Streptococcus suis and Streptococcus henryi of the genus Streptococcus, one candidate diguanylate cyclase was frequently identified. We demonstrate that both proteins encompass PAS (Per-ARNT-Sim)-GGDEF domains, possess diguanylate cyclase catalytic activity, and are suggested to signal via a PilZ receptor domain at the C-terminus of type 2 glycosyltransferase constituting BcsA cellulose synthases and a cellulose synthase-like protein CelA, respectively. Preservation of the ancient link between production of cellulose(-like) exopolysaccharides and c-di-GMP signaling indicates that this functionality is even of high ecological importance upon maintenance of the last remnants of a c-di-GMP signaling network in some of today's free-living bacteria.
Keywords: EAL domain; GGDEF domain; Proteus mirabilis; Streptococcus gallolyticus subsp. gallolyticus; cellulose biosynthesis; cyclic di-GMP signaling.