Cyclic di-GMP (c-di-GMP) has emerged as a bacterial second messenger that regulates a variety of cellular processes, in particular those associated with the switch between a motile and a sessile lifestyle. At low levels of c-di-GMP the motile lifestyle is favoured whereas at high levels of c-di-GMP the formation of biofilms is promoted.
In Pseudomonas aeruginosa, over 50 genes encoding proteins involved in the synthesis, hydrolysis or sensing of c-di-GMP are found and many remain uncharacterized. Herein, an analysis of a collection of mutants was performed and supported the idea that the sophisticated c-di-GMP network operates at high specificity.
In addition to c-di-GMP, P. aeruginosa has a regulatory pathway, the Gac pathway, that is known to control the bacterium lifestyle switch. By investigating a particular mutant affected in this pathway, a link between the Gac pathway and c-di-GMP was established.
Furthermore, the Gac pathway not only influences biofilm formation, but it is also crucial in determining the bacterium mode of infection. In other words, biofilm formation correlates to a chronic mode of infection where the bacterium has an active type VI secretion system (T6SS), and a motile phenotype correlates to an acute infection where the type III secretion system (T3SS) is active. Interestingly, by artificially modulating the levels of c-di-GMP it was demonstrated that c-di-GMP regulation goes beyond the control of the motile/sessile phenotypes and is able to inversely regulate the T3SS and T6SS.
Finally, the link between c-d-GMP and the Gac pathway was consolidated by showing that the Gac system impacts the expression of a few c-di-GMP related proteins and one protein, SadC, was identified as a central component of the network. Overall this work largely contributed to reconcile two independent concepts involved in the regulation of the P. aeruginosa lifestyle.