Control of bacterial exoelectrogenesis by c-AMP-GMP

Nelson, Jelani; Sudarsan, Narasimhan; Phillips, Grace E.; Stav, Shira; Lünse, Christina E.; McCown, Phillip J.; Breaker, Ronald R.

doi:10.1073/pnas.1419264112

Cited by 102 publications

(122 citation statements)

References 52 publications

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“…Thus, we demonstrate that cAG binding to the Gs1761 riboswitch aptamer disrupts terminator stem formation. Consistent with these results, an increase in full-length transcription with cAG was observed for another GEMM-Ib riboswitch (22). A key metabolic feature of the Geobacter genus is the ability to perform extracellular electron transfer.…”

supporting

confidence: 77%

GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP

Kellenberger¹,

Wilson²,

Hickey³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

120

146

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Cyclic dinucleotides are an expanding class of signaling molecules that control many aspects of bacterial physiology. A synthase for cyclic AMP-GMP (cAG, also referenced as 3′-5′, 3′-5′ cGAMP) called DncV is associated with hyperinfectivity of Vibrio cholerae but has not been found in many bacteria, raising questions about the prevalence and function of cAG signaling. We have discovered that the environmental bacterium Geobacter sulfurreducens produces cAG and uses a subset of GEMM-I class riboswitches (GEMM-Ib, Genes for the Environment, Membranes, and Motility) as specific receptors for cAG. GEMM-Ib riboswitches regulate genes associated with extracellular electron transfer; thus cAG signaling may control aspects of bacterial electrophysiology. These findings expand the role of cAG beyond organisms that harbor DncV and beyond pathogenesis to microbial geochemistry, which is important to environmental remediation and microbial fuel cell development. Finally, we have developed an RNA-based fluorescent biosensor for live-cell imaging of cAG. This selective, genetically encodable biosensor will be useful to probe the biochemistry and cell biology of cAG signaling in diverse bacteria.

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supporting

confidence: 77%

GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP

Kellenberger¹,

Wilson²,

Hickey³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

120

146

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“…All sequenced Geobacter and Pelobacter species have at least one Hypr enzyme (SI Appendix, Fig. S9) and have riboswitch effectors that regulate genes in response to cAG (17,18). A second Hypr is predicted in G. sulfurreducens, but GSU1937 was not active in the biosensor-based screen (Fig.…”

Section: Whereas Previous Ggdef Enzymes Were Uniformly Assigned As Dgmentioning

confidence: 99%

“…We and others recently discovered that Geobacter, a genus of deltaproteobacteria, use cAG-sensing riboswitches to regulate genes associated with extracellular electron transfer (17,18), an extraordinary activity that involves bacterial colonization on metal oxide surfaces (19). We further showed that Geobacter sulfurreducens produces cAG (17), but the synthase enzyme remained a mystery.…”

mentioning

confidence: 97%

Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3′, 3′-cGAMP)

Hallberg

Wang

Wright

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

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Over 30 years ago, GGDEF domain-containing enzymes were shown to be diguanylate cyclases that produce cyclic di-GMP (cdiG), a second messenger that modulates the key bacterial lifestyle transition from a motile to sessile biofilm-forming state. Since then, the ubiquity of genes encoding GGDEF proteins in bacterial genomes has established the dominance of cdiG signaling in bacteria. However, the observation that proteobacteria encode a large number of GGDEF proteins, nearing 1% of coding sequences in some cases, raises the question of why bacteria need so many GGDEF enzymes. In this study, we reveal that a subfamily of GGDEF enzymes synthesizes the asymmetric signaling molecule cyclic AMP-GMP (cAG or 3′, 3′-cGAMP). This discovery is unexpected because GGDEF enzymes function as symmetric homodimers, with each monomer binding to one substrate NTP. Detailed analysis of the enzyme from Geobacter sulfurreducens showed it is a dinucleotide cyclase capable of switching the major cyclic dinucleotide (CDN) produced based on ATP-to-GTP ratios. We then establish through bioinformatics and activity assays that hybrid CDN-producing and promiscuous substrate-binding (Hypr) GGDEF enzymes are found in other deltaproteobacteria. Finally, we validated the predictive power of our analysis by showing that cAG is present in surface-grown Myxococcus xanthus. This study reveals that GGDEF enzymes make alternative cyclic dinucleotides to cdiG and expands the role of this widely distributed enzyme family to include regulation of cAG signaling.bacterial signaling | surface sensing | second messengers | cyclic dinucleotides | fluorescent biosensor

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“…Some very rare riboswitch classes were discovered only because their representatives are very close derivatives of a more common riboswitch class, such as adenine or the 2 ′ -dG-I and -II riboswitches Weinberg et al 2017), all of which are variants of the vastly more common guanine riboswitch class initially discovered. Unfortunately, these close variants will remain hidden among the bioinformatics hits for a more prominent riboswitch class unless there are key distinctions, such as mutations to the ligand-binding core of the aptamer or gene associations that indicate a change in ligand specificity (Kellenberger et al 2015;Nelson et al 2015;Weinberg et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Riboswitch diversity and distribution

McCown

Corbino

Stav

et al. 2017

RNA

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401

516

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Riboswitches are commonly used by bacteria to detect a variety of metabolites and ions to regulate gene expression. To date, nearly 40 different classes of riboswitches have been discovered, experimentally validated, and modeled at atomic resolution in complex with their cognate ligands. The research findings produced since the first riboswitch validation reports in 2002 reveal that these noncoding RNA domains exploit many different structural features to create binding pockets that are extremely selective for their target ligands. Some riboswitch classes are very common and are present in bacteria from nearly all lineages, whereas others are exceedingly rare and appear in only a few species whose DNA has been sequenced. Presented herein are the consensus sequences, structural models, and phylogenetic distributions for all validated riboswitch classes. Based on our findings, we predict that there are potentially many thousands of distinct bacterial riboswitch classes remaining to be discovered, but that the rarity of individual undiscovered classes will make it increasingly difficult to find additional examples of this RNA-based sensory and gene control mechanism.

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Control of bacterial exoelectrogenesis by c-AMP-GMP

Cited by 102 publications

References 52 publications

GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP

GEMM-I riboswitches from Geobacter sense the bacterial second messenger cyclic AMP-GMP

Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3′, 3′-cGAMP)

Riboswitch diversity and distribution

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