Islet expression of type I interferon response sensors is associated with immune infiltration and viral infection in type 1 diabetes

Previous results indicate the presence of an interferon (IFN) signature in type 1 diabetes (T1D), capable of inducing chronic inflammation and compromising b cell function. Here, we determined the expression of the IFN response markers MxA, PKR, and HLA-I in the islets of autoantibody-positive and T1D donors. We found that these markers can be coexpressed in the same islet, are more abundant in insulin-containing islets, are highly expressed in islets with insulitis, and their expression levels are correlated with the presence of the enteroviral protein VP1. The expression of these markers was associated with down-regulation of multiple genes in the insulin secretion pathway. The coexistence of an IFN response and a microbial stress response is likely to prime islets for immune destruction. This study highlights the importance of therapeutic interventions aimed at eliminating potentially persistent infections and diminishing inflammation in individuals with T1D.

Silicate Fertilization Improves Microbial Functional Potential For Stress Tolerance in Arsenic-Enriched Rice Cropping Systems

Background: The host plant and its rhizosphere microbiome are similarly exposed to abiotic stresses under arsenic (As)-enriched cropping systems. Since silicon (Si) fertilization is effective in alleviating As-induced stresses in plants, and plant-microbe interactions are tightly coupled, we hypothesized that Si-fertilization would improve soil microbial functional potential to environmental stress tolerance, which was surprisingly not yet studied. With the help of high throughput metagenome, microarray and analyzing plant impacts on soil microbiome and the environment, we tested the hypothesis in two geographically different rice (i.e., Japonica and Indica) grown on As- enriched soils.Results: Silicate fertilization in rice grown on As-enriched soils altered rhizosphere bacterial communities and increased several commensal microorganisms and their genetic potential to tolerate oxidative stress, osmotic stress, oxygen limitation, nitrogen and phosphate limitation, heat and cold shock, and radiation stress. The stress resistant microbial communities shifted with the changes in rhizosphere nutrient flows and cumulative plant impacts on the soil environment.Conclusions: The study highlights a thus-far unexplored behavior of Si-fertilization to improve microbial stress resilience under As-laden cropping systems and open up promising avenue to further study how commonalities in plant-microbe signaling in response to Si-fertilization alleviates As-induced stresses in agro-systems.

The ups and downs of ectoine: structural enzymology of a major microbial stress protectant and versatile nutrient

Ectoine and its derivative 5-hydroxyectoine are compatible solutes and chemical chaperones widely synthesized by Bacteria and some Archaea as cytoprotectants during osmotic stress and high- or low-growth temperature extremes. The function-preserving attributes of ectoines led to numerous biotechnological and biomedical applications and fostered the development of an industrial scale production process. Synthesis of ectoines requires the expenditure of considerable energetic and biosynthetic resources. Hence, microorganisms have developed ways to exploit ectoines as nutrients when they are no longer needed as stress protectants. Here, we summarize our current knowledge on the phylogenomic distribution of ectoine producing and consuming microorganisms. We emphasize the structural enzymology of the pathways underlying ectoine biosynthesis and consumption, an understanding that has been achieved only recently. The synthesis and degradation pathways critically differ in the isomeric form of the key metabolite N-acetyldiaminobutyric acid (ADABA). γ-ADABA serves as preferred substrate for the ectoine synthase, while the α-ADABA isomer is produced by the ectoine hydrolase as an intermediate in catabolism. It can serve as internal inducer for the genetic control of ectoine catabolic genes via the GabR/MocR-type regulator EnuR. Our review highlights the importance of structural enzymology to inspire the mechanistic understanding of metabolic networks at the biological scale.

Enhanced metabolic potentials and functional gene interactions of microbial stress response towards high elevation in freshwater lakes

ABSTRACTElevation has strong influence on microbial community composition, but its influence on aquatic microbial functional genes remains unclear. Here, we compared the functional gene structure of microbial communities in surface water between two low-elevation lakes (LELs, with elevation of ca. 530 meters) and two high-elevation lakes (HELs, with elevation of ca. 4,600 meters) by using a metagenomic approach of Geo Chip-based functional gene arrays. We found significant differences in composition but not in richness of the microbial functional genes between the HELs and the LELs. In the HELs, the microbial communities had higher functional capacities in stress responses than those in LELs, which include cold shock, oxygen limitation, osmotic stress, nitrogen limitation, phosphate limitation, glucose limitation, radiation stress, heat shock, protein stress, and sigma factors genes. We also observed higher metabolic potentials in the degradation of aromatic, chitin, cellulose and hemicellulose in HELs than in LELs. By performing network analyses, we found enhanced interactions and complexity among the co-occurring functional genes in the HELs than those in the LELs in terms of network size, links, connectivity, and clustering coefficients. Notably, more functional genes of stress response played module-hub roles in the network of HELs. Overall, we observed contrasting patterns of microbial metabolic potentials and functional gene interactions in different elevational freshwater lakes, and found that the microbial communities developed functional strategies to cope with the harsh conditions at the high elevational lakes.IMPORTANCEElevational patterns of biodiversity have attracted scientific interest in the fields of microbial ecology and biogeography. The influence of elevation on aquatic microbial functional gene structure and their metabolic potentials remains unclear. We compared the functional gene structure of microbial communities in surface water between two low-elevation lakes and two high-elevation lakes with a more than 4,000-meter difference in elevation along a mountainside by using GeoChip 5.0, which covered in total 144,000 gene sequences from 393 functional gene families. We found apparent differences in functional gene structures in lakes between the two different elevations. We also found enhanced metabolic potentials and functional gene interactions for microbial stress response with increasing elevation in freshwater lakes. These results highlighted that limnetic microbial communities could develop functional strategies to cope with harsh conditions towards high elevations.

Degradation of the microbial stress protectants and chemical chaperones ectoine and hydroxyectoine by a bacterial hydrolase–deacetylase complex

When faced with increased osmolarity in the environment, many bacterial cells accumulate the compatible solute ectoine and its derivative 5-hydroxyectoine. Both compounds are not only potent osmostress protectants, but also serve as effective chemical chaperones stabilizing protein functionality. Ectoines are energy-rich nitrogen and carbon sources that have an ecological impact that shapes microbial communities. Although the biochemistry of ectoine and 5-hydroxyectoine biosynthesis is well understood, our understanding of their catabolism is only rudimentary. Here, we combined biochemical and structural approaches to unravel the core of ectoine and 5-hydroxy-ectoine catabolisms. We show that a conserved enzyme bimodule consisting of the EutD ectoine/5-hydroxyectoine hydrolase and the EutE deacetylase degrades both ectoines. We determined the high-resolution crystal structures of both enzymes, derived from the salt-tolerant bacteria Ruegeria pomeroyi and Halomonas elongata. These structures, either in their apo-forms or in forms capturing substrates or intermediates, provided detailed insights into the catalytic cores of the EutD and EutE enzymes. The combined biochemical and structural results indicate that the EutD homodimer opens the pyrimidine ring of ectoine through an unusual covalent intermediate, N-α-2 acetyl-l-2,4-diaminobutyrate (α-ADABA). We found that α-ADABA is then deacetylated by the zinc-dependent EutE monomer into diaminobutyric acid (DABA), which is further catabolized to l-aspartate. We observed that the EutD–EutE bimodule synthesizes exclusively the α-, but not the γ-isomers of ADABA or hydroxy–ADABA. Of note, α-ADABA is known to induce the MocR/GabR-type repressor EnuR, which controls the expression of many ectoine catabolic genes clusters. We conclude that hydroxy–α-ADABA might serve a similar function.

Linking regional shifts in microbial genome adaptation with surface ocean biogeochemistry

Linking ‘omics measurements with biogeochemical cycles is a widespread challenge in microbial community ecology. Here, we propose applying genomic adaptation as ‘biosensors’ for microbial investments to overcome nutrient stress. We then integrate this genomic information with a trait-based model to predict regional shifts in the elemental composition of marine plankton communities. We evaluated this approach using metagenomic and particulate organic matter samples from the Atlantic, Indian and Pacific Oceans. We find that our genome-based trait model significantly improves our prediction of particulate C : P (carbon : phosphorus) across ocean regions. Furthermore, we detect previously unrecognized ocean areas of iron, nitrogen and phosphorus stress. In many ecosystems, it can be very challenging to quantify microbial stress. Thus, a carefully calibrated genomic approach could become a widespread tool for understanding microbial responses to environmental changes and the biogeochemical outcomes. This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.