Cyclic nucleotides in bacteria.

The question of the ubiquity of cyclic AMP in bacteria is not yet closed. The recent introduction of more sensitive and reliable assays for cyclic AMP should settle the problem. My prediction is that although there may be some organisms that do not contain cyclic AMP, they probably have some yet undiscovered regulatory nucleotides that play similar roles. Although cyclic AMP has been shown to be unessential for growth of E. coli under optimal laboratory conditions in glucose-containing medium, it undoubtedly can play a role in survival. Cyclic AMP allows bacteria to adapt to a variety of new nutritional conditions. The significance of the observations that cyclic AMP shows a concentration-dependent stimulation or inhibition of growth rate in E. coli is not yet clear. The pathways regulated by cyclic AMP are, for the most part, those which involve carbon metabolism. On the other hand, pathways of nitrogen metabolism are not uniformly regulated by cyclic AMP. In several organisms, some nitrogen pathways are regulated by glutamine synthetase. Specialized processes such as the formation of flagella, fruiting bodies, and buds often appear to be controlled by cyclic AMP. This is similar to the situation in mammalian cells wherein many differentiated functions are regulated by cyclic AMP. Catabolite repression can be explained by an inhibition of the synthesis of cyclic AMP, which does not require an invocation of a primary effect of catabolite action on cyclic AMP phosphodiesterase or on a secretory process, although these two processes are probably of secondary importance. There are some fundamental similarities between the effects of catabolites in inhibiting E. coli adenylyl cyclase and the effects of hormones on mammalian adenylyl cyclase. Both processes require the interaction of the effector with a membrane-bound receptor and may transmit the inhibitory or stimulatory signal to adenylyl cyclase via some coupling factor. Cyclic GMP is clearly present in bacteria, although the features of its molecular biology are just beginning to be laid out. How many other regulatory nucleotides, whether cyclic or linear, remain to be found in bacteria is a problem for the future.