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Gut bacteria can affect key aspects of host fitness, such as development, fecundity, and lifespan, while the host, in turn, shapes the gut microbiome. However, it is unclear to what extent individual species versus community interactions within the microbiome are linked to host fitness. Here, we combinatorially dissect the natural microbiome of Drosophila melanogaster and reveal that interactions between bacteria shape host fitness through life history tradeoffs. Empirically, we made germ-free flies colonized with each possible combination of the five core species of fly gut bacteria. We measured the resulting bacterial community abundances and fly fitness traits, including development, reproduction, and lifespan. The fly gut promoted bacterial diversity, which, in turn, accelerated development, reproduction, and aging: Flies that reproduced more died sooner. From these measurements, we calculated the impact of bacterial interactions on fly fitness by adapting the mathematics of genetic epistasis to the microbiome. Development and fecundity converged with higher diversity, suggesting minimal dependence on interactions. However, host lifespan and microbiome abundances were highly dependent on interactions between bacterial species. Higher-order interactions (involving three, four, and five species) occurred in 13–44% of possible cases depending on the trait, with the same interactions affecting multiple traits, a reflection of the life history tradeoff. Overall, we found these interactions were frequently context-dependent and often had the same magnitude as individual species themselves, indicating that the interactions can be as important as the individual species in gut microbiomes.

The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. To investigate host specificity, we used gnotobiotic Drosophila , microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization. Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus species physically remodels the niche through production of a glycan-rich secretion to favor secondary colonization by unrelated commensals in the Acetobacter genus. Our results provide a mechanistic framework for understanding the establishment and stability of a multi-species intestinal microbiome. Animal gut microbiomes are fairly stable over time despite large daily fluctuations in diet and introductions of environmental bacteria. Here the authors report that fruit flies maintain the stability of their microbiome in part through a physical niche in the esophagus.

Predicting antibiotic efficacy within microbial communities remains highly challenging. Interspecies interactions can impact antibiotic activity through many mechanisms, including alterations to bacterial physiology. Here, we studied synthetic communities constructed from the core members of the fruit fly gut microbiota. Co-culturing of Lactobacillus plantarum with Acetobacter species altered its tolerance to the transcriptional inhibitor rifampin. By measuring key metabolites and environmental pH, we determined that Acetobacter species counter the acidification driven by L. plantarum production of lactate. Shifts in pH were sufficient to modulate L. plantarum tolerance to rifampin and the translational inhibitor erythromycin. A reduction in lag time exiting stationary phase was linked to L. plantarum tolerance to rifampicin, opposite to a previously identified mode of tolerance to ampicillin in E. coli. This mechanistic understanding of the coupling among interspecies interactions, environmental pH, and antibiotic tolerance enables future predictions of growth and the effects of antibiotics in more complex communities.

ObjectiveTo develop and validate a calculator to predict the risk of in-hospital mortality in patients with active infective endocarditis (IE) undergoing cardiac surgery.MethodsThousand two hundred and ninety-nine consecutive patients with IE were prospectively recruited (1996–2014) and retrospectively analysed. Left-sided patients who underwent cardiac surgery (n=671) form our study population and were randomised into development (n=424) and validation (n=247) samples. Variables statistically significant to predict in-mortality were integrated in a multivariable prediction model, the Risk-Endocarditis Score (RISK-E). The predictive performance of the score and four existing surgical scores (European System for Cardiac Operative Risk Evaluation (EuroSCORE) I and II), Prosthesis, Age ≥70, Large Intracardiac Destruction, Staphylococcus, Urgent Surgery, Sex (Female) (PALSUSE), EuroSCORE ≥10) and Society of Thoracic Surgeons’s Infective endocarditis score (STS-IE)) were assessed and compared in our cohort. Finally, an external validation of the RISK-E in a separate population was done.ResultsVariables included in the final model were age, prosthetic infection, periannular complications, Staphylococcus aureus or fungi infection, acute renal failure, septic shock, cardiogenic shock and thrombocytopaenia. Area under the receiver operating characteristic curve in the validation sample was 0.82 (95% CI 0.75 to 0.88). The accuracy of the other surgical scores when compared with the RISK-E was inferior (p=0.010). Our score also obtained a good predictive performance, area under the curve 0.76 (95% CI 0.64 to 0.88), in the external validation.ConclusionsIE-specific factors (microorganisms, periannular complications and sepsis) beside classical variables in heart surgery (age, haemodynamic condition and renal failure) independently predicted perioperative mortality in IE. The RISK-E had better ability to predict surgical mortality in patients with IE when compared with other surgical scores.

The ongoing conflict between viruses and their hosts can drive the co-evolution between host immune genes and viral suppressors of immunity. It has been suggested that an evolutionary 'arms race' may occur between rapidly evolving components of the antiviral RNAi pathway of Drosophila and viral genes that antagonize it. We have recently shown that viral protein 1 (VP1) of Drosophila melanogaster Nora virus (DmelNV) suppresses Argonaute-2 (AGO2)-mediated target RNA cleavage (slicer activity) to antagonize antiviral RNAi. Here we show that viral AGO2 antagonists of divergent Nora-like viruses can have host specific activities. We have identified novel Nora-like viruses in wild-caught populations of D. immigrans (DimmNV) and D. subobscura (DsubNV) that are 36% and 26% divergent from DmelNV at the amino acid level. We show that DimmNV and DsubNV VP1 are unable to suppress RNAi in D. melanogaster S2 cells, whereas DmelNV VP1 potently suppresses RNAi in this host species. Moreover, we show that the RNAi suppressor activity of DimmNV VP1 is restricted to its natural host species, D. immigrans. Specifically, we find that DimmNV VP1 interacts with D. immigrans AGO2, but not with D. melanogaster AGO2, and that it suppresses slicer activity in embryo lysates from D. immigrans, but not in lysates from D. melanogaster. This species-specific interaction is reflected in the ability of DimmNV VP1 to enhance RNA production by a recombinant Sindbis virus in a host-specific manner. Our results emphasize the importance of analyzing viral RNAi suppressor activity in the relevant host species. We suggest that rapid co-evolution between RNA viruses and their hosts may result in host species-specific activities of RNAi suppressor proteins, and therefore that viral RNAi suppressors could be host-specificity factors.

Gut microbes were previously suggested to influence mate preference in Drosophila melanogaster. Mate selectivity depended on the microbiota associated with flies after prior generations were maintained on different diets [cornmeal-molasses-yeast versus starch]. Subsequent studies attempted to repeat these findings with contrasting success. We suggest that a nonstandardized, transient microbiota -- and how it is influenced by diet and dietary additives -- might account for the conflicting results. A point of contention between the studies is that a fungicide used in fly media, methylparaben (mp) -- also known as Tegosept or Nipagin M -- might affect bacterial growth and thus microbiota composition. Although Leftwich et al. argued that moderate mp (up to 0.3%) should not alter microbiota, a previous study suggested that high mp levels (~0.5%) can impact microbiota diversity. How mp concentration affects individual, fly-associated microbes on fly media has not been systematically addressed.

The ongoing conflict between viruses and their hosts can drive the co-evolution between host immune genes and viral suppressors of immunity. It has been suggested that an evolutionary 'arms race' may occur between rapidly evolving components of the antiviral RNAi pathway of Drosophila and viral genes that antagonize it. We have recently shown that viral protein 1 (VP1) of Drosophila melanogaster Nora virus (DmelNV) suppresses Argonaute-2 (AGO2)-mediated target RNA cleavage (slicer activity) to antagonize antiviral RNAi. Here we show that viral AGO2 antagonists of divergent Nora-like viruses can have host specific activities. We have identified novel Nora-like viruses in wild-caught populations of D. immigrans (DimmNV) and D. subobscura (DsubNV) that are 36% and 26% divergent from DmelNV at the amino acid level. We show that DimmNV and DsubNV VP1 are unable to suppress RNAi in D. melanogaster S2 cells, whereas DmelNV VP1 potently suppresses RNAi in this host species. Moreover, we show that the RNAi suppressor activity of DimmNV VP1 is restricted to its natural host species, D. immigrans. Specifically, we find that DimmNV VP1 interacts with D. immigrans AGO2, but not with D. melanogaster AGO2, and that it suppresses slicer activity in embryo lysates from D. immigrans, but not in lysates from D. melanogaster. This species-specific interaction is reflected in the ability of DimmNV VP1 to enhance RNA production by a recombinant Sindbis virus in a host-specific manner. Our results emphasize the importance of analyzing viral RNAi suppressor activity in the relevant host species. We suggest that rapid co-evolution between RNA viruses and their hosts may result in host species-specific activities of RNAi suppressor proteins, and therefore that viral RNAi suppressors could be host-specificity factors.

This thesis is devoted to understanding and modeling multimaterial interactions, and to develop accordingly a robust scheme taking into account the largest variety of those, with a particular interest in resolving solid/fluid configurations. This very general frame of studies can be tackled with numerous different approaches as several issues arise and need to be addressed before attempting any modelisation of these problems. A first questioning should be the frame of reference to be used for the materials considered. Eulerian shock-capturing schemes have advantages for modeling problems involving complex non-linear wave structures and large deformations. If originally reserved mostly to fluids components, recent work has focused on extending Eulerian schemes to other media such as solid dynamics, as long as the set of equations employed is written under a hyperbolic system of conservation laws. Another matter of interest when dealing with multiple immiscible materials it the necessity to include some means of tracking material boundaries within a numerical scheme. Interface tracking methods based on the use of level set functions are an attractive alternative for problems with sliding interfaces since it allows discontinuous velocity profiles at the material boundaries whilst employing fixed grids. However, its intrinsic lack of variables conservation needs to be circumvented by applying an appropriate fix near the interface, where cells might comprise multiple components. Another requirement is the ability to correctly predict the physical interaction at the interface between the materials. For that purpose, the Riemann problem corresponding to the interfacial conditions needs to be formulated and solved. This implies in turn the need of appropriate Riemann solvers; if they are largely available when the materials are identical (i.e. governed by the same set of equations), a specific Riemann solver will be developed to account for fluid/solid interaction. Eventually, these newly developed methods will be tested on a wide range of different multimaterial problems, involving several materials undergoing large deformations. The materials used, whether modelling fluid/fluid or solid/fluid interactions, will be tested using various initial conditions from both sides of the interface, to demonstrate the robustness of the solver and its flexibility. These testcases will be carried out in 1D, 2D and 3D frames, and compared to exact solutions or other numerical experiments conducted in previous studies.

Animals throughout the metazoa selectively acquire specific symbiotic gut bacteria from their environment that aid host fitness. Current models of colonization suggest these bacteria use weakly specific receptors to stick to host tissues and that colonization results when they stick in a region of the host gut that overlaps with their nutritional niche. An alternative model is that unique receptor-ligand binding interactions provide specificity for target niches. Here we use live imaging of individual symbiotic bacterial cells colonizing the gut of living Drosophila melanogaster to show that Lactiplantibacillus plantarum specifically recognizes a distinct physical niche in the host gut. We find that recognition is controlled by a colonization island that is widely conserved in commensals and pathogens from the Lactobacillales to the Clostridia. Our findings indicate a genetic mechanism of host specificity that is broadly conserved. Host-symbiont specificity is encoded by a conserved colonization island that provides molecular precision to host niche access.

The intestines of animals are typically colonized by a complex, relatively stable microbiota that influences health and fitness, but the underlying mechanisms of colonization remain poorly understood. As a typical animal, the fruit fly, Drosophila melanogaster, is associated with a consistent set of commensal bacterial species, yet the reason for this consistency is unknown. Here, we use gnotobiotic flies, microscopy, and microbial pulse-chase protocols to show that a commensal niche exists within the proventriculus region of the Drosophila foregut that selectively binds bacteria with exquisite strain-level specificity. Primary colonizers saturate the niche and exclude secondary colonizers of the same strain, but initial colonization by Lactobacillus physically remodels the niche to favor secondary colonization by Acetobacter. Our results provide a mechanistic framework for understanding the establishment and stability of an intestinal microbiome. A strain-specific set of bacteria inhabits a defined spatial region of the Drosophila gut that forms a commensal niche.