- Email: [email protected]
Microbial Ecology: Functional ‘Modules’ Drive Assembly of Polysaccharide-Degrading Marine Microbial Communities
Current Biology
Dispatches Microbial Ecology: Functional ‘Modules’ Drive Assembly of Polysaccharide-Degrading Marine Microbial Communities Stephen R. Lindemann1,2,* 1Whistler
Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN, USA of Nutrition Science, Purdue University, West Lafayette, IN, USA *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.03.056 2Department
Although ecological principles governing the competition of microbes for simple substrates are wellunderstood, less is known about how complex, structured substrates influence ecological outcomes in microbial communities. A new study sheds light on how marine microbial communities assemble on polysaccharide particles modeling marine snow. Understanding ecological responses of microbial communities to the complex, structured substrates common in the natural environment remains a central challenge of microbial ecology. The mathematical relationship between resource availability and microbial growth on simple sugars like glucose has been known for over half a century [1]. Furthermore, the ecology of microbial competition for these simple substrates (that is, those that can be directly transported into the cell and metabolized) by multiple microbes is well known [2]. As predicted by the competitive exclusion principle in ecology (also known as Gause’s Law [3]), any advantage of one species in growth on a substrate will, over time, lead to dominance of the better competitor; in contrast, the inferior one will either go extinct or avoid competition (for example, by adopting a new niche) [4]. Fierce competition for simple sugars typically keeps their environmental concentrations low [5]. However, the ecology of microbial communities that degrade much more environmentally abundant polysaccharides — those that are too large to be transported into the cell and require secreted degradative enzymes to break them into transportable monomers and oligomers — remains poorly understood. The ecology of polysaccharide consumption is central to the functioning of many important microbial systems, impacting processes as large as global carbon flux [5] and as personal as human and animal health [6]. Consumption of a complex polysaccharide has different effects upon
the ecology of microbial communities than does the consumption of a simple substrate like glucose. Sugar monomers and oligomers are available to any organism in the community that can transport and degrade them, as their small size allows them to fit through transporter proteins into the cell. In contrast, however, larger oligomers and polymers are too large to be easily transported by most microbes, and typically require hydrolysis outside the cell to produce breakdown products that can be transported. Therefore, in the context of a more complex substrate, the external degradation of substrates by microbes that possess the required degradative enzymes has the capacity to produce ‘public goods’ (simpler sugars and other metabolic by-products) that cross-feed other organisms lacking the ability to hydrolyze the complex substrate, thereby stabilizing diverse ecological interactions [7]. Recent studies suggest that microbial communities are indeed adapted for increased cooperativity in degradation of polysaccharides. For example, some assemblages of marine isolates exhibited synergistic growth on the polysaccharides cellulose and xylan but not when grown on glucose [8]. Additionally, these same communities displayed less inhibition of other species when growing on polysaccharides when compared with growth on glucose [9]. The ability to predict microbial community assembly and dynamics is a key challenge in microbial ecology and hinges upon our understanding of how
R330 Current Biology 29, R317–R339, May 6, 2019 ª 2019 Elsevier Ltd.
organisms compete and cooperate, dividing metabolic labor as they degrade complex substrates like polysaccharides. Work reported in this issue of Current Biology sheds light on the dynamics of polysaccharide-degrading marine microbial communities, revealing that their assembly and dynamics depend not on species but on the functional ‘modules’ they possess [10] (Figure 1). Incubating particles composed of the polysaccharides commonly produced by marine phototrophs (agarose, chitin, alginate, and carrageenan) embedded in magnetic hydrogels in surface seawater, the authors demonstrated that the initial assembly of particle-attached microbial communities was dominated by polysaccharide-specific primary degraders. However, these communities reproducibly gave way to dominance by a similar set of secondary degraders across all of the polysaccharides tested. These successions revealed a bimodal association between the specificity of an alternative sequence variant (ASV, a computational proxy for a set of microbial genotypes identical across the sequenced region of the 16S ribosomal RNA gene) for the polysaccharide embedded in the particle; organisms were either highly specific for one of the four polysaccharides (specialists) or highly unspecific, being successful on all of them (generalists). The authors recapitulated the ecology of these interactions using isolates from the incubations, showing that prior cultivation of a specialist Psychromonas isolate supported the growth of five generalist microbes otherwise unable to
Current Biology
grow on alginate. Genomic analysis of this specialist revealed extensive enzymatic machinery to hydrolyze and utilize alginate; in contrast, generalist microbes either possessed only the ability to import and consume smaller polysaccharidederived oligosaccharides or lacked even this ability. Metabolomic analysis of the specialist-derived spent medium, before and after cultivation of generalists, revealed consumption of the metabolic byproducts of specialist growth, such as amino acids, nucleotides, and tricarboxylic acid cycle intermediates. Interestingly, leakage and utilization of these metabolic products by primary degraders supports the hypothesis that they also support generalist populations independently of their production of lower-molecular-weight oligosaccharides and monosaccharides as public goods [11]. Metabolic cross-feeding of nonpolysaccharide-degrading microbes by degraders is important in maintaining diversity in other marine systems [12] as well as in host-associated [13,14] and engineered [15] microbial ecosystems. To further test the hypothesis that assembly on polysaccharide particles was based upon functional groups rather than individual species, the authors investigated the assembly of mixed polysaccharide particles (agarose– alginate and agarose–carrageenan) incubated in the same seawater used for the single-polysaccharide experiments. Using the relative abundances of ASVs as inputs, the authors constructed a set of linear models to predict their abundances on mixed-polysaccharide particles. These computational models displayed good agreement with the experimental results, consistent with the hypothesis that community assembly and dynamics on these polysaccharide particles depends more on functional role than species identity. Essentially, so long as the appropriate primary degrader module for the polysaccharide is present, succession continues along similar trajectories for all polysaccharides, presumably because similar nutrients are available. Further, it suggests the possibility that assembly and succession may be predictable for any given polysaccharide structure and an initial pool of species. This observation will require further experimentation with diverse assemblages of marine microbiota to determine whether the observed result
Succession
Dispatches
Polysaccharides
Oligo- and monosaccharides
Primary degrader
Secondary colonizers
Metabolic products
Current Biology
Figure 1. Functional modularity in polysaccharide degradation governs microbial succession on marine polysaccharide particles. Polysaccharide structures (blue and green chains) govern the initial recruitment of specific primary degrader organisms possessing the functional modules required for their consumption. Polysaccharide hydrolysis likely releases oligosaccharides and monosaccharides, as well as metabolic products of the primary degrader organism. These hydrolysis and metabolic products sustain largely shared groups of secondary consumers, resulting in similarity across polysaccharides late in succession. When mixed, the stoichiometry of polysaccharides controls the early assembly of polysaccharide degraders, but results in similar dynamics later in succession.
was specific to the populations captured in the sample described here or whether it holds generally true across multiple seawater samples. In a sense, the one job of the primary degraders in marine ecosystems is to liberate and convert detrital, phototrophderived carbon entrapped in polysaccharides for use by secondary consumer organisms. Once the job is predominantly finished, and a diverse particle-associated community established, primary degraders flee the particle in search of another one, repeating the process [16]. The present study adds to this that the assemblage of primary degraders on such particles is initially polysaccharide-specific, but thereafter succession dynamics are largely general. As the vast majority (by mass) of phototroph-derived nutrients are bound in biological polymers [5], this suggests the notion that primary phototrophs — along with the specific degraders of the most abundant polysaccharides produced by these phototrophs — should perhaps together be considered coupled carbon-
cycling ‘teams’ in the lit regions of marine ecosystems, together functioning as keystone species that support diverse generalist populations. These data also suggest the possibility that polysaccharides, due likely to the tight correspondence between carbohydrate structure and the specificity of enzymes for carbohydrate linkages [17], provide a certain number of independent niches that primary degraders can fill, based upon which functional modules their genomes encode. This would suggest that the idea of the functional module may be better considered at even higher levels of structural resolution than consumption of a certain type of polysaccharide, such as at the level of specific carbohydrate linkages (or other structural motifs within a polysaccharide). The polysaccharides studied in this report are relatively simple in structure (largely linear polymers with one or two different glycosyl residues and one or two types of linkages among those residues) and divorced from their native physical forms, so relatively fewer genes
Current Biology 29, R317–R339, May 6, 2019 R331
Current Biology
Dispatches may be required for their hydrolysis in the described system. However, in their natural context of cell walls, the number of niches they afford (and the functional modules required to exploit them) may be considerably greater. This study lays a firm foundation for future work on microbial succession on marine detritus particles by suggesting that the polysaccharide structures present may govern the rate, fate, and dynamics of their degradation and, in turn, influence marine carbon flux. More generally, it advances our understanding of the functional modularity of polysaccharide degradation by microbes, which may govern ecology in diverse environmental and host-associated microbiomes.
4. Xu, C., and Yuan, S. (2016). Competition in the chemostat: A stochastic multi-species model and its asymptotic behavior. Math. Biosci. 280, 1–9.
REFERENCES
9. Deng, Y.-J., and Wang, S.Y. (2017). Complex carbohydrates reduce the frequency of antagonistic interactions among bacteria degrading cellulose and xylan. FEMS Microbiol. Lett. 364, fnx019.
5. Mu¨hlenbruch, M., Grossart, H.-P., Eigemann, F., and Voss, M. (2018). Phytoplanktonderived polysaccharides in the marine environment and their interactions with heterotrophic bacteria. Environ. Microbiol. 20, 2671–2685. 6. Hamaker, B.R., and Tuncil, Y.E. (2014). A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J. Mol. Biol. 426, 3838–3850. 7. Konopka, A., Lindemann, S., and Fredrickson, J. (2015). Dynamics in microbial communities: unraveling mechanisms to identify principles. ISME J. 9, 1488–1495. 8. Deng, Y.-J., and Wang, S.Y. (2016). Synergistic growth in bacteria depends on substrate complexity. J. Microbiol. 54, 23–30.
1. Monod, J. (1949). The growth of bacterial cultures. Annu. Rev. Microbiol. 3, 371–394. 2. Hansen, S.R., and Hubbell, S.P. (1980). Singlenutrient microbial competition: qualitative agreement between experimental and theoretically forecast outcomes. Science 207, 1491–1493. 3. Gause, G.F. (1932). Experimental studies on the struggle for existence: I. mixed population of two species of yeast. J. Exp. Biol. 9, 389–402.
10. Enke, T.N., Datta, M.S., Schwartzman, J., Cermak, N., Schmitz, D., Barrere, J., PascualGarcı´a, A., and Cordero, O.X. (2019). Modular assembly of polysaccharide-degrading marine microbial communities. Curr. Biol. 29, 1528– 1535. 11. Reintjes, G., Arnosti, C., Fuchs, B.M., and Amann, R. (2017). An alternative
polysaccharide uptake mechanism of marine bacteria. ISME J. 11, 1640–1650. 12. Wietz, M., Wemheuer, B., Simon, H., Giebel, H.-A., Seibt, M.A., Daniel, R., Brinkhoff, T., and Simon, M. (2015). Bacterial community dynamics during polysaccharide degradation at contrasting sites in the Southern and Atlantic Oceans. Environ. Microbiol. 17, 3822– 3831. 13. Belenguer, A., Duncan, S.H., Calder, A.G., Holtrop, G., Louis, P., Lobley, G.E., and Flint, H.J. (2006). Two routes of metabolic crossfeeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl. Env. Microbiol. 72, 3593– 3599. 14. Solden, L.M., Naas, A.E., Roux, S., Daly, R.A., Collins, W.B., Nicora, C.D., Purvine, S.O., Hoyt, D.W., Schu¨ckel, J., Jørgensen, B., et al. (2018). Interspecies cross-feeding orchestrates carbon degradation in the rumen ecosystem. Nat. Microbiol. 3, 1274–1284. 15. Lubbe, A., Bowen, B.P., and Northen, T. (2017). Exometabolomic analysis of crossfeeding metabolites. Metabolites 7, 50. 16. Datta, M.S., Sliwerska, E., Gore, J., Polz, M.F., and Cordero, O.X. (2016). Microbial interactions lead to rapid micro-scale successions on model marine particles. Nat. Commun. 7, 11965. 17. Abbott, D.W., and van Bueren, A.L. (2014). Using structure to inform carbohydrate binding module function. Curr. Opin. Struct. Biol. 28, 32–40.
Virology: Poxins Soothe the STING Alexiane Decout1 and Andrea Ablasser1,*
de rale de Lausanne, 1015 Lausanne, Switzerland Health Institute, Ecole Polytechnique Fe *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.03.031
1Global
The mammalian cyclic dinucleotide 2’,3’-cGAMP is a potent inducer of innate immune responses produced upon detection of cytosolic DNA by cGAS. The mechanisms underlying the control of intracellular cGAMP levels remained unclear. In a new study, Eaglesham et al. identified poxins as 2’,3’-cGAMP-specific nucleases allowing immune evasion by viruses. cGAS (cyclic GMP-AMP synthase) and STING (Stimulator of interferon gene) form a major immune signaling axis allowing the detection of cytosolic DNA, a critical danger signal. Upon viral infection or cellular damage, cGAS binds to cytosolic dsDNA and synthesizes a second messenger—cyclic dinucleotide 2’,3’-cyclic GMP AMP (also referred to
as 2’,3’-cGAMP) [1]. This molecule is detected by STING, which then translocates from the endoplasmic reticulum to the Golgi apparatus to activate a downstream signaling cascade, ultimately leading to the production of antiviral type I interferon [2]. Activation of the cGAS–STING pathway is tightly regulated at several levels in order
R332 Current Biology 29, R317–R339, May 6, 2019 ª 2019 Elsevier Ltd.
to avoid excessive inflammation upon encountering self-DNA. Cytosolic DNAses, such as TREX1, that constantly degrade DNA leaking from the nucleus [3] serve as important safeguards. cGAS itself is an interferon-stimulated gene, and is only upregulated when needed to protect the host cell [4]. Likewise, STING activation requires several post-translational
Dispatches Microbial Ecology: Functional ‘Modules’ Drive Assembly of Polysaccharide-Degrading Marine Microbial Communities Stephen R. Lindemann1,2,* 1Whistler
Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN, USA of Nutrition Science, Purdue University, West Lafayette, IN, USA *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.03.056 2Department
Although ecological principles governing the competition of microbes for simple substrates are wellunderstood, less is known about how complex, structured substrates influence ecological outcomes in microbial communities. A new study sheds light on how marine microbial communities assemble on polysaccharide particles modeling marine snow. Understanding ecological responses of microbial communities to the complex, structured substrates common in the natural environment remains a central challenge of microbial ecology. The mathematical relationship between resource availability and microbial growth on simple sugars like glucose has been known for over half a century [1]. Furthermore, the ecology of microbial competition for these simple substrates (that is, those that can be directly transported into the cell and metabolized) by multiple microbes is well known [2]. As predicted by the competitive exclusion principle in ecology (also known as Gause’s Law [3]), any advantage of one species in growth on a substrate will, over time, lead to dominance of the better competitor; in contrast, the inferior one will either go extinct or avoid competition (for example, by adopting a new niche) [4]. Fierce competition for simple sugars typically keeps their environmental concentrations low [5]. However, the ecology of microbial communities that degrade much more environmentally abundant polysaccharides — those that are too large to be transported into the cell and require secreted degradative enzymes to break them into transportable monomers and oligomers — remains poorly understood. The ecology of polysaccharide consumption is central to the functioning of many important microbial systems, impacting processes as large as global carbon flux [5] and as personal as human and animal health [6]. Consumption of a complex polysaccharide has different effects upon
the ecology of microbial communities than does the consumption of a simple substrate like glucose. Sugar monomers and oligomers are available to any organism in the community that can transport and degrade them, as their small size allows them to fit through transporter proteins into the cell. In contrast, however, larger oligomers and polymers are too large to be easily transported by most microbes, and typically require hydrolysis outside the cell to produce breakdown products that can be transported. Therefore, in the context of a more complex substrate, the external degradation of substrates by microbes that possess the required degradative enzymes has the capacity to produce ‘public goods’ (simpler sugars and other metabolic by-products) that cross-feed other organisms lacking the ability to hydrolyze the complex substrate, thereby stabilizing diverse ecological interactions [7]. Recent studies suggest that microbial communities are indeed adapted for increased cooperativity in degradation of polysaccharides. For example, some assemblages of marine isolates exhibited synergistic growth on the polysaccharides cellulose and xylan but not when grown on glucose [8]. Additionally, these same communities displayed less inhibition of other species when growing on polysaccharides when compared with growth on glucose [9]. The ability to predict microbial community assembly and dynamics is a key challenge in microbial ecology and hinges upon our understanding of how
R330 Current Biology 29, R317–R339, May 6, 2019 ª 2019 Elsevier Ltd.
organisms compete and cooperate, dividing metabolic labor as they degrade complex substrates like polysaccharides. Work reported in this issue of Current Biology sheds light on the dynamics of polysaccharide-degrading marine microbial communities, revealing that their assembly and dynamics depend not on species but on the functional ‘modules’ they possess [10] (Figure 1). Incubating particles composed of the polysaccharides commonly produced by marine phototrophs (agarose, chitin, alginate, and carrageenan) embedded in magnetic hydrogels in surface seawater, the authors demonstrated that the initial assembly of particle-attached microbial communities was dominated by polysaccharide-specific primary degraders. However, these communities reproducibly gave way to dominance by a similar set of secondary degraders across all of the polysaccharides tested. These successions revealed a bimodal association between the specificity of an alternative sequence variant (ASV, a computational proxy for a set of microbial genotypes identical across the sequenced region of the 16S ribosomal RNA gene) for the polysaccharide embedded in the particle; organisms were either highly specific for one of the four polysaccharides (specialists) or highly unspecific, being successful on all of them (generalists). The authors recapitulated the ecology of these interactions using isolates from the incubations, showing that prior cultivation of a specialist Psychromonas isolate supported the growth of five generalist microbes otherwise unable to
Current Biology
grow on alginate. Genomic analysis of this specialist revealed extensive enzymatic machinery to hydrolyze and utilize alginate; in contrast, generalist microbes either possessed only the ability to import and consume smaller polysaccharidederived oligosaccharides or lacked even this ability. Metabolomic analysis of the specialist-derived spent medium, before and after cultivation of generalists, revealed consumption of the metabolic byproducts of specialist growth, such as amino acids, nucleotides, and tricarboxylic acid cycle intermediates. Interestingly, leakage and utilization of these metabolic products by primary degraders supports the hypothesis that they also support generalist populations independently of their production of lower-molecular-weight oligosaccharides and monosaccharides as public goods [11]. Metabolic cross-feeding of nonpolysaccharide-degrading microbes by degraders is important in maintaining diversity in other marine systems [12] as well as in host-associated [13,14] and engineered [15] microbial ecosystems. To further test the hypothesis that assembly on polysaccharide particles was based upon functional groups rather than individual species, the authors investigated the assembly of mixed polysaccharide particles (agarose– alginate and agarose–carrageenan) incubated in the same seawater used for the single-polysaccharide experiments. Using the relative abundances of ASVs as inputs, the authors constructed a set of linear models to predict their abundances on mixed-polysaccharide particles. These computational models displayed good agreement with the experimental results, consistent with the hypothesis that community assembly and dynamics on these polysaccharide particles depends more on functional role than species identity. Essentially, so long as the appropriate primary degrader module for the polysaccharide is present, succession continues along similar trajectories for all polysaccharides, presumably because similar nutrients are available. Further, it suggests the possibility that assembly and succession may be predictable for any given polysaccharide structure and an initial pool of species. This observation will require further experimentation with diverse assemblages of marine microbiota to determine whether the observed result
Succession
Dispatches
Polysaccharides
Oligo- and monosaccharides
Primary degrader
Secondary colonizers
Metabolic products
Current Biology
Figure 1. Functional modularity in polysaccharide degradation governs microbial succession on marine polysaccharide particles. Polysaccharide structures (blue and green chains) govern the initial recruitment of specific primary degrader organisms possessing the functional modules required for their consumption. Polysaccharide hydrolysis likely releases oligosaccharides and monosaccharides, as well as metabolic products of the primary degrader organism. These hydrolysis and metabolic products sustain largely shared groups of secondary consumers, resulting in similarity across polysaccharides late in succession. When mixed, the stoichiometry of polysaccharides controls the early assembly of polysaccharide degraders, but results in similar dynamics later in succession.
was specific to the populations captured in the sample described here or whether it holds generally true across multiple seawater samples. In a sense, the one job of the primary degraders in marine ecosystems is to liberate and convert detrital, phototrophderived carbon entrapped in polysaccharides for use by secondary consumer organisms. Once the job is predominantly finished, and a diverse particle-associated community established, primary degraders flee the particle in search of another one, repeating the process [16]. The present study adds to this that the assemblage of primary degraders on such particles is initially polysaccharide-specific, but thereafter succession dynamics are largely general. As the vast majority (by mass) of phototroph-derived nutrients are bound in biological polymers [5], this suggests the notion that primary phototrophs — along with the specific degraders of the most abundant polysaccharides produced by these phototrophs — should perhaps together be considered coupled carbon-
cycling ‘teams’ in the lit regions of marine ecosystems, together functioning as keystone species that support diverse generalist populations. These data also suggest the possibility that polysaccharides, due likely to the tight correspondence between carbohydrate structure and the specificity of enzymes for carbohydrate linkages [17], provide a certain number of independent niches that primary degraders can fill, based upon which functional modules their genomes encode. This would suggest that the idea of the functional module may be better considered at even higher levels of structural resolution than consumption of a certain type of polysaccharide, such as at the level of specific carbohydrate linkages (or other structural motifs within a polysaccharide). The polysaccharides studied in this report are relatively simple in structure (largely linear polymers with one or two different glycosyl residues and one or two types of linkages among those residues) and divorced from their native physical forms, so relatively fewer genes
Current Biology 29, R317–R339, May 6, 2019 R331
Current Biology
Dispatches may be required for their hydrolysis in the described system. However, in their natural context of cell walls, the number of niches they afford (and the functional modules required to exploit them) may be considerably greater. This study lays a firm foundation for future work on microbial succession on marine detritus particles by suggesting that the polysaccharide structures present may govern the rate, fate, and dynamics of their degradation and, in turn, influence marine carbon flux. More generally, it advances our understanding of the functional modularity of polysaccharide degradation by microbes, which may govern ecology in diverse environmental and host-associated microbiomes.
4. Xu, C., and Yuan, S. (2016). Competition in the chemostat: A stochastic multi-species model and its asymptotic behavior. Math. Biosci. 280, 1–9.
REFERENCES
9. Deng, Y.-J., and Wang, S.Y. (2017). Complex carbohydrates reduce the frequency of antagonistic interactions among bacteria degrading cellulose and xylan. FEMS Microbiol. Lett. 364, fnx019.
5. Mu¨hlenbruch, M., Grossart, H.-P., Eigemann, F., and Voss, M. (2018). Phytoplanktonderived polysaccharides in the marine environment and their interactions with heterotrophic bacteria. Environ. Microbiol. 20, 2671–2685. 6. Hamaker, B.R., and Tuncil, Y.E. (2014). A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J. Mol. Biol. 426, 3838–3850. 7. Konopka, A., Lindemann, S., and Fredrickson, J. (2015). Dynamics in microbial communities: unraveling mechanisms to identify principles. ISME J. 9, 1488–1495. 8. Deng, Y.-J., and Wang, S.Y. (2016). Synergistic growth in bacteria depends on substrate complexity. J. Microbiol. 54, 23–30.
1. Monod, J. (1949). The growth of bacterial cultures. Annu. Rev. Microbiol. 3, 371–394. 2. Hansen, S.R., and Hubbell, S.P. (1980). Singlenutrient microbial competition: qualitative agreement between experimental and theoretically forecast outcomes. Science 207, 1491–1493. 3. Gause, G.F. (1932). Experimental studies on the struggle for existence: I. mixed population of two species of yeast. J. Exp. Biol. 9, 389–402.
10. Enke, T.N., Datta, M.S., Schwartzman, J., Cermak, N., Schmitz, D., Barrere, J., PascualGarcı´a, A., and Cordero, O.X. (2019). Modular assembly of polysaccharide-degrading marine microbial communities. Curr. Biol. 29, 1528– 1535. 11. Reintjes, G., Arnosti, C., Fuchs, B.M., and Amann, R. (2017). An alternative
polysaccharide uptake mechanism of marine bacteria. ISME J. 11, 1640–1650. 12. Wietz, M., Wemheuer, B., Simon, H., Giebel, H.-A., Seibt, M.A., Daniel, R., Brinkhoff, T., and Simon, M. (2015). Bacterial community dynamics during polysaccharide degradation at contrasting sites in the Southern and Atlantic Oceans. Environ. Microbiol. 17, 3822– 3831. 13. Belenguer, A., Duncan, S.H., Calder, A.G., Holtrop, G., Louis, P., Lobley, G.E., and Flint, H.J. (2006). Two routes of metabolic crossfeeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl. Env. Microbiol. 72, 3593– 3599. 14. Solden, L.M., Naas, A.E., Roux, S., Daly, R.A., Collins, W.B., Nicora, C.D., Purvine, S.O., Hoyt, D.W., Schu¨ckel, J., Jørgensen, B., et al. (2018). Interspecies cross-feeding orchestrates carbon degradation in the rumen ecosystem. Nat. Microbiol. 3, 1274–1284. 15. Lubbe, A., Bowen, B.P., and Northen, T. (2017). Exometabolomic analysis of crossfeeding metabolites. Metabolites 7, 50. 16. Datta, M.S., Sliwerska, E., Gore, J., Polz, M.F., and Cordero, O.X. (2016). Microbial interactions lead to rapid micro-scale successions on model marine particles. Nat. Commun. 7, 11965. 17. Abbott, D.W., and van Bueren, A.L. (2014). Using structure to inform carbohydrate binding module function. Curr. Opin. Struct. Biol. 28, 32–40.
Virology: Poxins Soothe the STING Alexiane Decout1 and Andrea Ablasser1,*
de rale de Lausanne, 1015 Lausanne, Switzerland Health Institute, Ecole Polytechnique Fe *Correspondence: [email protected] https://doi.org/10.1016/j.cub.2019.03.031
1Global
The mammalian cyclic dinucleotide 2’,3’-cGAMP is a potent inducer of innate immune responses produced upon detection of cytosolic DNA by cGAS. The mechanisms underlying the control of intracellular cGAMP levels remained unclear. In a new study, Eaglesham et al. identified poxins as 2’,3’-cGAMP-specific nucleases allowing immune evasion by viruses. cGAS (cyclic GMP-AMP synthase) and STING (Stimulator of interferon gene) form a major immune signaling axis allowing the detection of cytosolic DNA, a critical danger signal. Upon viral infection or cellular damage, cGAS binds to cytosolic dsDNA and synthesizes a second messenger—cyclic dinucleotide 2’,3’-cyclic GMP AMP (also referred to
as 2’,3’-cGAMP) [1]. This molecule is detected by STING, which then translocates from the endoplasmic reticulum to the Golgi apparatus to activate a downstream signaling cascade, ultimately leading to the production of antiviral type I interferon [2]. Activation of the cGAS–STING pathway is tightly regulated at several levels in order
R332 Current Biology 29, R317–R339, May 6, 2019 ª 2019 Elsevier Ltd.
to avoid excessive inflammation upon encountering self-DNA. Cytosolic DNAses, such as TREX1, that constantly degrade DNA leaking from the nucleus [3] serve as important safeguards. cGAS itself is an interferon-stimulated gene, and is only upregulated when needed to protect the host cell [4]. Likewise, STING activation requires several post-translational