Genomic Features Of A Bumble Bee Symbiont Reflect Its Host Environment

Here, we report the genome of one gammaproteobacterial member of the gut microbiota, for which we propose the name >Candidatus Schmidhempelia bombi,> that was inadvertently sequenced alongside the genome of its host, the bumble bee, Bombus impatiens. This symbiont is a member of the recently described bacterial order Orbales, which has been collected from the guts of diverse insect species; however, >Ca. Schmidhempelia> has been identified exclusively with bumble bees. Metabolic reconstruction reveals that >Ca. Schmidhempelia> lacks many genes for a functioning NADH dehydrogenase I, all genes for the high-oxygen cytochrome o, and most genes in the tricarboxylic acid (TCA) cycle. >Ca. Schmidhempelia> has retained NADH dehydrogenase II, the low-oxygen specific cytochrome bd, anaerobic nitrate respiration, mixed-acid fermentation pathways, and citrate fermentation, which may be important for survival in low-oxygen or anaerobic environments found in the bee hindgut. Additionally, a type 6 secretion system, a Flp pilus, and many antibiotic/multidrug transporters suggest complex interactions with its host and other gut commensals or pathogens. This genome has signatures of reduction (2.0 megabase pairs) and rearrangement, as previously observed for genomes of host-associated bacteria. A survey of wild and laboratory B. impatiens revealed that >Ca. Schmidhempelia> is present in 90% of individuals and, therefore, may provide benefits to its host.Center for Insect Science (University of Arizona)National Science Foundation NSF 1046153NIH Director's Pioneer 1DP1OD006416-01NIH R01-HG006677Swiss National Science Foundation 140157, 147881Integrative Biolog

A simple and distinctive microbiota exclusively associated with honey bees and bumble bees

Abstract: Specialized relationships with bacteria often allow animals to exploit a new diet by providing a novel set of metabolic capabilities. Bees are a monophyletic group of Hymenoptera that transitioned to a completely herbivorous diet from the carnivorous diet of their wasp ancestors. Recent culture-independent studies suggest that a set of distinctive bacterial species inhabits the gut of the honey bee, Apis mellifera. Here we survey the gut microbiotae of diverse bee and wasp species to test whether acquisition of these bacteria was associated with the transition to herbivory in bees generally. We found that most bee species lack phylotypes that are the same or similar to those typical of A. mellifera, rejecting the hypothesis that this dietary transition was symbiont-dependent. The most common bacteria in solitary bee species are a widespread phylotype of Burkholderia and the pervasive insect associate, Wolbachia. In contrast, several social representatives of corbiculate bees do possess distinctive bacterial phylotypes. Samples of A. mellifera harboured the same microbiota as in previous surveys, and closely related bacterial phylotypes were identified in two Asian honey bees (Apis andreniformis and Apis dorsata) and several bumble bee (Bombus) species. Potentially, the sociality of Apis and Bombus species facilitates symbiont transmission and thus is key to the maintenance of a more consistent gut microbiota. Phylogenetic analyses provide a more refined taxonomic placement of the A. mellifera symbionts. apis mellifera | bacterial microbiota | insect symbiosis | microbiology | molecula

Winter and spring controls on the summer food web of the coastal West Antarctic Peninsula

Understanding the mechanisms by which climate variability affects multiple trophic levels in food webs is essential for determining ecosystem responses to climate change. Here we use over two decades of data collected by the Palmer Long Term Ecological Research program (PAL-LTER) to determine how large-scale climate and local physical forcing affect phytoplankton, zooplankton and an apex predator along the West Antarctic Peninsula (WAP). We show that positive anomalies in chlorophyll-a (chl-a) at Palmer Station, occurring every 4-6 years, are constrained by physical processes in the preceding winter/spring and a negative phase of the Southern Annular Mode (SAM). Favorable conditions for phytoplankton included increased winter ice extent and duration, reduced spring/summer winds, and increased water column stability via enhanced salinity-driven density gradients. Years of positive chl-a anomalies are associated with the initiation of a robust krill cohort the following summer, which is evident in Adelie penguin diets, thus demonstrating tight trophic coupling. Projected climate change in this region may have a significant, negative impact on phytoplankton biomass, krill recruitment and upper trophic level predators in this coastal Antarctic ecosystem

Symbionts as Major Modulators of Insect Health: Lactic Acid Bacteria and Honeybees

Lactic acid bacteria (LAB) are well recognized beneficial host-associated members of the microbiota of humans and animals. Yet LAB-associations of invertebrates have been poorly characterized and their functions remain obscure. Here we show that honeybees possess an abundant, diverse and ancient LAB microbiota in their honey crop with beneficial effects for bee health, defending them against microbial threats. Our studies of LAB in all extant honeybee species plus related apid bees reveal one of the largest collections of novel species from the genera Lactobacillus and Bifidobacterium ever discovered within a single insect and suggest a long (>80 mya) history of association. Bee associated microbiotas highlight Lactobacillus kunkeei as the dominant LAB member. Those showing potent antimicrobial properties are acquired by callow honey bee workers from nestmates and maintained within the crop in biofilms, though beekeeping management practices can negatively impact this microbiota. Prophylactic practices that enhance LAB, or supplementary feeding of LAB, may serve in integrated approaches to sustainable pollinator service provision. We anticipate this microbiota will become central to studies on honeybee health, including colony collapse disorder, and act as an exemplar case of insect-microbe symbiosis

A National Study of Multiple Organ Dysfunction after Trauma: Contemporary Patterns of Severity and Recovery

Background: The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level. Methods: Adult patients admitted to major trauma centre critical care units were enrolled in this 4‐week point‐prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes. Results: Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24‐hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003). Conclusion: Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Ecological and Evolutionary Relationships between Bees and their Bacterial Gut Microbiota

Gut microbial communities exist in the vast majority of animals, and often form complex symbioses with their hosts that affect their host's biology in numerous ways. To date, the majority of studies of these complex interactions have focused on the nutritional benefits provided by the microbiota; however, the natural microbiota can also influence development, immunity, and the metabolism of its host. Apis mellifera, the honey bee, harbors a distinctive bacterial community that is present in individuals from distant locations around the world; however, the basis of the bee-microbiota association is unknown. This dissertation explores properties of the bacterial microbiota within bees, including its persistence of this association, mechanisms of transmission, localization through host ontogeny, and basic metabolic capabilities that define and maintain the symbiotic relationship. Apis and Bombus species (honey and bumble bees) share a distinct bacterial microbiota that is not present in other bees and wasps. Close analysis of the A. mellifera microbiota revealed consistent communities in adult worker gut organs and a general lack of bacteria in larvae. Contact between workers and with hive materials were identified as major routes of transmission for bacterial communities, showing the importance of social behavior in this association. Genomic analysis of a gut bacterium co-sequenced with the Bombus impatiens genome revealed it as a divergent lineage of Gammaproteobacteria, and deletions of conserved metabolic pathways, reduction in genome size, and its low GC content all suggest that the bacterial species has had a long association with its host.Release after 24-Apr-201

Ecological and evolutionary relationships between bees and their bacterial gut microbiota

Gut microbial communities exist in the vast majority of animals, and often form complex symbioses with their hosts that affect their host's biology in numerous ways. To date, the majority of studies of these complex interactions have focused on the nutritional benefits provided by the microbiota; however, the natural microbiota can also influence development, immunity, and the metabolism of its host. Apis mellifera, the honey bee, harbors a distinctive bacterial community that is present in individuals from distant locations around the world; however, the basis of the bee-microbiota association is unknown. This dissertation explores properties of the bacterial microbiota within bees, including its persistence of this association, mechanisms of transmission, localization through host ontogeny, and basic metabolic capabilities that define and maintain the symbiotic relationship. Apis and Bombus species (honey and bumble bees) share a distinct bacterial microbiota that is not present in other bees and wasps. Close analysis of the A. mellifera microbiota revealed consistent communities in adult worker gut organs and a general lack of bacteria in larvae. Contact between workers and with hive materials were identified as major routes of transmission for bacterial communities, showing the importance of social behavior in this association. Genomic analysis of a gut bacterium co-sequenced with the Bombus impatiens genome revealed it as a divergent lineage of Gammaproteobacteria, and deletions of conserved metabolic pathways, reduction in genome size, and its low GC content all suggest that the bacterial species has had a long association with its host