Gene regulation in Pseudomonas aeruginosa by c-di-GMP-dependent thermotransduction

Abstract

Bacterial signal transduction by the second messenger cyclic diguanylate (c-di-GMP) is used by many bacteria to adapt to changing conditions inside or outside of the cell. Bioinformatics have revealed a vast collection of sensory domains in enzymes that carry out the production and degradation of c-di-GMP. However, despite recent advances in understanding mechanisms of sensory perception in c-di-GMP networks, the vast majority of the putative sensory domains in c-di-GMP metabolizing enzymes lack ascribed functions. Here, I describe the bacterial thermosensory diguanylate cyclase (TdcA) from Pseudomonas aeruginosa, which fine tunes intracellular c-di-GMP levels in response to temperature. My research reveals that the thermosensory functions of TdcA are mediated by a thermosensitive Per-Arnt-SIM (thermoPAS) domain, which is a function not previously ascribed to the widespread family of PAS protein domains. Using RNA-sequencing, I investigated the effects of c-di-GMP produced by TdcA on the P. aeruginosa transcriptome at different temperatures. My results identify that c-di-GMP synthesized by TdcA regulates an expansive repertoire of genes involved in stress resistance, ribosome assembly, and horizontal gene transfer. Moreover, most of these genes comprise part of the P. aeruginosa accessory genome. Altogether, this body of work not only identifies a group of c-di-GMP metabolizing enzymes that function as molecular thermosensory devices, but also defines a process of c-di-GMP-dependent thermotransduction in P. aeruginosa.