The ins and outs of cyclic di-GMP signaling in Vibrio cholerae

Conner, Jenna G.; Zamorano‐Sánchez, David; Park, Jin Hwan; Sondermann, Holger; Yildiz, Fitnat H.

doi:10.1016/j.mib.2017.01.002

Cited by 126 publications

(133 citation statements)

References 62 publications

(82 reference statements)

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“…Regardless of the source of these alterations, the expression changes we see are not fully consistent with a shift toward high or low levels of either cyclic dinucleotide. We see several gene changes consistent with high di-cGMP [31] (increased MSHA biosynthesis, increased cold shock, decreased heat shock, and increased type VI secretion expression (S2 Table)) and some changes consistent with low di-cGMP [31] (increased flagellar synthesis and increased expression of the virulence regulator ToxT (S2 Table)). An increase in MSHA is also consistent with low cGAMP, but we also see downregulation of some chemotaxis associated genes, and chemotaxis is repressed by high cGAMP [32].…”

Section: Introductionmentioning

confidence: 89%

“…It is hard to predict with certainty which transcriptional changes are a defensive host response to infection and which are due to transcriptional manipulation on the part of ICP1. Many of the differentially expressed genes relate to phenotypes regulated by cyclic di-GMP (di-cGMP) [31]. Recently, another cyclic dinucleotide, cyclic GMP-AMP (cGAMP), which was first discovered in V. cholerae [32], has been linked to phage defense [33].…”

Section: Introductionmentioning

confidence: 99%

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A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

Barth

Netter

Angermeyer

et al. 2020

Preprint

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Many viruses possess temporally unfolding gene expression patterns aimed at subverting host defenses, commandeering host metabolism, and ultimately producing a large number of progeny virions. High throughput -omics tools, such as RNA-seq, have dramatically enhanced resolution of expression patterns during infection. Less studied have been viral satellites, mobile genomes that parasitize viruses and have far reaching effects on host-cell fitness. By performing RNA-seq on infection time courses, we have obtained the first time-resolved transcriptomes for bacteriophage satellites during lytic infection. Specifically, we have acquired transcriptomes for the lytic Vibrio cholerae phage ICP1 and all five known variants of ICP1's parasite, the Phage Inducible Chromosomal Island-Like Elements (PLEs). PLEs rely on ICP1 for both DNA replication and mobilization, and abolish production of ICP1 progeny in infected cells. We investigated PLEs impact on ICP1 gene expression and found that PLEs did not broadly restrict or reduce ICP1 gene expression. A major exception occurred in ICP1's capsid morphogenesis operon, which was downregulated by each of the PLE variants. This transcriptional manipulation, conserved among PLEs, has also evolved independently in at least one other phage satellite, suggesting that viral satellites may be under strong selective pressure to reduce the capsid expression of their larger host viruses. Surprisingly, PLEs were also found to alter the gene expression of CTXφ, the integrative phage that encodes cholera toxin and is necessary for virulence of toxigenic V. cholerae. One PLE, PLE1, upregulated CTXφ genes involved in replication and integration, and boosted CTXφ mobility following induction of the SOS response. Our data show that PLEs exhibit conserved manipulation of their host-phage's gene expression, but divergent effects on CTXφ, revealing that PLEs can influence both their hosts' resistance to phage and the mobility of virulence encoding elements.So far, few insights have been gained into the gene expression programs of ICP1 and PLEs. PLE1 expresses its integrase in uninfected cells [22], expression of PLE1's replication initiator, RepA, is induced following infection of ICP1 [23], and the PLE's lysis modulator, LidI, is detectable by Western blot late during ICP1 infection [25]. The PLE integrase's recombination directionality factor (necessary for directing integrase excision activity) is PexA, an ICP1 protein whose native function is unknown, but whose expression can be detected by 5 minutes post infection [22]. While these limited observations have provided insight into key PLE and ICP1 genes, the gross expression patterns of ICP1 and PLEs remain unknown. Until now, we have not known the degree to which ICP1 alters cellular expression patterns, and whether PLEs alter ICP1's gene expression or reproduce and restrict ICP1 without such alterations. To address these questions, we performed RNA-seq on V. cholerae infected by ICP1 over the course of the infection cycle. We sequenced the transc...

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

Barth

Netter

Angermeyer

et al. 2020

Preprint

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“…Levels of c-di-GMP are modulated by two classes of cellular enzymes, diguanylate cyclases (which contain GGDEF motifs) and cyclic diguanylate phosphodiesterases (which contain EAL/HD-GYP motifs) (114,115). In V. cholerae, V. vulnificus, V. parahaemolyticus, and likely other vibrios, c-di-GMP is critical for coordinating biofilm formation and motility (116)(117)(118)(119)(120). LuxR homologs regulate the expression of a number of genes encoding diguanylate cyclases and cyclic diguanylate phosphodiesterases (Fig.…”

Section: Luxr/hapr Regulation Of Group Behaviors In Vibriosmentioning

confidence: 99%

Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios

2017

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The coordination of group behaviors in bacteria is accomplished via the cell-cell signaling process called quorum sensing. Vibrios have historically been models for studying bacterial communication due to the diverse and remarkable behaviors controlled by quorum sensing in these bacteria, including bioluminescence, type III and type VI secretion, biofilm formation, and motility. Here, we discuss the Vibrio LuxR/HapR family of proteins, the master global transcription factors that direct downstream gene expression in response to changes in cell density. These proteins are structurally similar to TetR transcription factors but exhibit distinct biochemical and genetic features from TetR that determine their regulatory influence on the quorum sensing gene network. We review here the gene groups regulated by LuxR/ HapR and quorum sensing and explore the targets that are common and unique among Vibrio species.

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“…Cyclic bis(3’→5’) dimeric guanosine monophosphate (c-di-GMP) is a widespread bacterial second messenger that regulates a variety of processes, including DNA repair, transcription, mRNA decay, motility, protein and polysaccharide secretion, cell development, and biofilm formation (1-4). Cyclic di-GMP has a well-documented contribution to virulence of such important human pathogens as Vibrio cholerae, Pseudomonas aeruginosa, Salmonella enterica, Borrelia (Borreliella) burgdorferi , and Yersinia pestis and plant pathogens such as Xanthomonas campestris and X. citri (1, 3, 5-7). Cellular responses to c-di-GMP-dependent signaling are mediated by specific receptors, which include two types of riboswitches and a wide variety of c-di-GMP-binding proteins.…”

Section: Introductionmentioning

confidence: 99%

Structural conservation and diversity of PilZ-related domains

Galperin

Chou

2019

Preprint

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The widespread bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a 1 variety of processes, including protein secretion, motility, cell development, and biofilm 2 formation. C-di-GMP-dependent responses are often mediated by its binding to the 3 cytoplasmic receptors that contain the PilZ domain. We present here comparative 4 structural and sequence analysis of various PilZ-related domains and describe three 5 principal types of them: (i) the canonical PilZ domain, whose structure includes a six-6 stranded beta-barrel and a C-terminal alpha-helix; (ii) an atypical PilZ domain that 7 contains two extra alpha-helices and forms stable tetramers, and (iii) divergent PilZ-8 related domains, which include the eponymous PilZ protein and PilZN (YcgR_N) and 9 PilZNR (YcgR_2) domains. We refine the second c-di-GMP binding motif of PilZ as 10 [D/N]hSxxG and show that the hydrophobic residue h of this motif interacts with a cluster 11 of conserved hydrophobic residues, helping maintain the PilZ domain fold. We describe 12 several novel PilZN-type domains that are fused to the canonical PilZ domains in specific 13 taxa, such as spirochetes, actinobacteria, cellulosolytic clostridia, deltaproteobacteria, 14 and aquificae. We propose that the evolution of three major groups of PilZ domains 15 included (i) fusion of pilZ with other genes, which produced Alg44, cellulose synthase, and 16 other multidomain proteins; (ii) insertion of a ~200-bp fragment, which resulted in the 17 formation of tetramer-forming PilZ proteins, and (iii) tandem duplication of pilZ genes, 18 which led to the formation of PilZ dimers and YcgR-like proteins. 19 IMPORTANCE 20Cyclic di-GMP is a ubiquitous bacterial second messenger that regulates motility, biofilm 21 formation and virulence of many bacterial pathogens. The PilZ domain is a widespread c-22 di-GMP receptor that binds c-di-GMP through its RxxxR and [D/N]xSxxG motifs; some PilZ 23 domains lack these motifs and are unable to bind c-di-GMP. We used structural and 24 sequence analysis to assess the diversity of PilZ-related domains and define their common 25 features. We show that the hydrophobic residue h in the second motif is highly conserved; 26 it may serve as a readout for c-di-GMP binding. We describe three principal classes of 27 PilZ-related domains: canonical, tetramer-forming, and divergent PilZ domains, and 28 propose the evolutionary pathways that led to the emergence of these PilZ types. 29 30

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The ins and outs of cyclic di-GMP signaling in Vibrio cholerae

Cited by 126 publications

References 62 publications

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

Quorum Sensing Gene Regulation by LuxR/HapR Master Regulators in Vibrios

Structural conservation and diversity of PilZ-related domains

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