Abstract
Bacteria have the option of initiating adaptive transcription to deal with the stress or to form a defensive community of a biofilm in order to survive. Here, we identified how bacteria utilize a modular toolkit of signaling proteins with exchangeable domains to survive in adverse environments. Two serine/threonine phosphatases activate the general stress response in B. subtilis, but how sensor proteins transduce species-specific signals to initiate the response is not known. Here we report the regulatory mechanism by which these phosphatases are activated. Both phosphatases require the phosphatase domains to be in the correct dimeric conformation in order for there to be metal cofactor binding and activation. Importantly, we present evidence that related coiled-coil linkers and phosphatase dimers transduce signals from diverse sensor domains to control the General Stress Response and other signaling across bacterial phyla. Additionally, we have shown that two unrelated members of this signaling toolkit come together to regulate biofilm formation in S. aureus. These biofilms assemble during infections or under laboratory conditions by growth on medium containing glucose, but the intracellular signal for biofilm formation and its downstream targets were unknown. Previous work identified genes needed for the release of extracellular DNA, including the gene for the cyclic-di-AMP phosphodiesterase GdpP, Biofilm formation is triggered by a drop in second messenger nucleotide cyclic-di-AMP. We additionally show that the downstream consequence of the drop in cyclic-di-AMP is inhibition of the “accessory gene regulator” operon agr, which is known to suppress biofilm formation through phosphorylation of the transcriptional regulator AgrA by the histidine kinase AgrC. Surprisingly we find that GdpP directly binds to autophosphorylated AgrC, which inhibits phosphotransfer to AgrA, allowing for biofilm formation. These results additionally resolve the mystery of how shared sensory domains control serine/threonine phosphatases, diguanylate cyclases and histidine kinases, revealing a common coiled-coil linker transduction mechanism.