Abstract
Cyclic guanosine 3′,5′-monophosphate (cyclic GMP) is a second messenger whose role in bacterial signalling is poorly understood. A genetic screen in the plant pathogen Xanthomonas campestris (Xcc) identified that XC_0250, which encodes a protein with a class III nucleotidyl cyclase domain, is required for cyclic GMP synthesis. Purified XC_0250 was active in cyclic GMP synthesis in vitro. The linked gene XC_0249 encodes a protein with a cyclic mononucleotide-binding (cNMP) domain and a GGDEF diguanylate cyclase domain. The activity of XC_0249 in cyclic di-GMP synthesis was enhanced by addition of cyclic GMP. The isolated cNMP domain of XC_0249 bound cyclic GMP and a structure–function analysis, directed by determination of the crystal structure of the holo-complex, demonstrated the site of cyclic GMP binding that modulates cyclic di-GMP synthesis. Mutation of either XC_0250 or XC_0249 led to a reduced virulence to plants and reduced biofilm formation in vitro. These findings describe a regulatory pathway in which cyclic GMP regulates virulence and biofilm formation through interaction with a novel effector that directly links cyclic GMP and cyclic di-GMP signalling.
Highlights
Signal transduction pathways involving cyclic nucleotide second messengers occur in all domains of life where theyReceived: 13 May 2013; accepted: 4 July 2013; published online: 23 July 20132430 The EMBO Journal VOL 32 | NO 18 | 2013 act to link perception of environmental or intracellular cues and signal to specific alterations in cellular function
We further show that these regulatory effects of cyclic GMP are exerted in part by a diguanylate cyclase (DGC) whose activity in cyclic di-GMP synthesis is responsive to cyclic GMP
As far as we are aware, this is the first description of the role of cyclic GMP in bacterial biofilm formation or in the virulence of a bacterial pathogen
Summary
Signal transduction pathways involving cyclic nucleotide second messengers occur in all domains of life where theyReceived: 13 May 2013; accepted: 4 July 2013; published online: 23 July 20132430 The EMBO Journal VOL 32 | NO 18 | 2013 act to link perception of environmental or intracellular cues and signal to specific alterations in cellular function. Signal transduction leading to encystment involves a cyclic GMP-responsive transcription factor that is a homologue of CRP, the cyclic AMP-responsive transcription factor found in other bacteria Beyond these observations, the distribution of cyclic GMP signalling in bacteria, the diversity of processes that are regulated and how regulation is exerted remain largely unknown. The distribution of cyclic GMP signalling in bacteria, the diversity of processes that are regulated and how regulation is exerted remain largely unknown This lack of knowledge contrasts with the body of work on cyclic di-GMP signalling, which shows that in diverse bacteria this nucleotide regulates a range of functions including developmental transitions, biofilm formation, motility and virulence via interactions with different classes of effector molecule (Hengge, 2009; Sondermann et al, 2012; Srivastava and Waters, 2012; Ryan et al, 2012b; Romling et al, 2013)
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