Garlic Inhibits Inflammation during Dengue Infection

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. There has been a recent global trend of increased epidemic activity, and DENV infection is considered a serious emerging health problem worldwide. A relatively unexplored approach to develop new treatments for dengue virus infection and the prevention of severe disease development is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during the host response to dengue virus infection. Several studies have proposed that it is the oxidative stress response induced by dengue virus infection that is responsible for triggering the pro-inflammatory cytokine cascade. Thus, blocking the oxidative stress response and reducing inflammation could together reduce the likelihood of severe disease development. Garlic has been shown to have several health benefits, and many of these are thought to be due to the reduction of inflammation. Garlic has also been shown to have effects on the oxidative stress response and prevent intracellular glutathione depletion. Here, we hypothesized that garlic could reduce inflammation during dengue virus infection through the reduction of the oxidative stress response. Our results indicate that garlic active compounds reduce inflammation during dengue virus infection and show that this reduction is due to the effects on the oxidative stress response. These results suggest that garlic could be used as an alternative treatment for dengue virus infection and for the prevention of severe disease development

Adaptive sampling in context-aware systems: a machine learning approach

As computing systems become ever more pervasive, there is an increasing need for them to understand and adapt to the state of the environment around them: that is, their context. This understanding comes with considerable reliance on a range of sensors. However, portable devices are also very constrained in terms of power, and hence the amount of sensing must be minimised. In this paper, we present a machine learning architecture for context awareness which is designed to balance the sampling rates (and hence energy consumption) of individual sensors with the significance of the input from that sensor. This significance is based on predictions of the likely next context. The architecture is implemented using a selected range of user contexts from a collected data set. Simulation results show reliable context identification results. The proposed architecture is shown to significantly reduce the energy requirements of the sensors with minimal loss of accuracy in context identification

Experimental evolution with bacteria in complex environments

Experiments with microbes are a powerful tool for addressing general questions in evolutionary ecology. Microbial evolution is also interesting in its own right, and often clinically relevant. I have used experimental evolution of bacteria (Pseudomonas spp.) in controlled laboratory environments to investigate the role of environmental heterogeneity in the evolution of phenotypic diversity. Some of my results provide insight on general processes, while others are specific to bacteria. (1) I have shown that variation in resource supply affects the evolution of niche breadth in complex environments containing a range of available resources, leading to a peak in phenotypic diversity at intermediate levels. (2) I have found that resource availability also affects selection against redundant phenotypic characters, which is strongest when resources are scarce. (3) Using experiments with bacteria and their protozoan predators, I have found that selection for predator resistance varies with resource supply during a model adaptive radiation. (4) I have looked at the role of periodic bottlenecks in population size in the evolution of antibiotic-resistant bacteria. My results highlight the importance of biochemical constraints specific to different resistance mutations. (5) Finally, I have shown that bacterial adaptation to novel carbon substrates affects different growth parameters simultaneously, and that the same response is seen in environments that maintain different levels of phenotypic diversity. These findings emphasize the role of environmental heterogeneity in the evolution of phenotypic diversity, but also show how ecological and genetic factors can constrain adaptation to a given niche within a heterogeneous environment

Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria

Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance

Coevolutionary dynamics shape the structure of bacteria‐phage infection networks

Coevolution—reciprocal evolutionary change among interacting species driven by natural selection—is thought to be an important force in shaping biodiversity. This ongoing process takes place within tangled networks of species interactions. In microbial communities, evolutionary change between hosts and parasites occurs at the same time scale as ecological change. Yet, we still lack experimental evidence of the role of coevolution in driving changes in the structure of such species interaction networks. Filling this gap is important because network structure influences community persistence through indirect effects. Here, we quantified experimentally to what extent coevolutionary dynamics lead to contrasting patterns in the architecture of bacteria–phage infection networks. Specifically, we look at the tendency of these networks to be organized in a nested pattern by which the more specialist phages tend to infect only a proper subset of those bacteria infected by the most generalist phages. We found that interactions between coevolving bacteria and phages become less nested over time under fluctuating dynamics, and more nested under arms race dynamics. Moreover, when coevolution results in high average infectivity, phages and bacteria differ more from each other over time under arms race dynamics than under fluctuating dynamics. The tradeoff between the fitness benefits of evolving resistance/infectivity traits and the costs of maintaining them might explain these differences in network structure. Our study shows that the interaction pattern between bacteria and phages at the community level depends on the way coevolution unfolds.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149309/1/evo13731_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149309/2/evo13731.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149309/3/evo13731-sup-0001-TableS1.pd

In Vitro Gut Modeling as a Tool for Adaptive Evolutionary Engineering of Lactiplantibacillus plantarum

Research and marketing of probiotics demand holistic strain improvement considering both the biotic and abiotic gut environment. Here, we aim to establish the continuous in vitro colonic fermentation model PolyFermS as a tool for adaptive evolutionary engineering. Immobilized fecal microbiota from adult donors were steadily cultivated up to 72 days in PolyFermS reactors, providing a long-term compositional and functional stable ecosystem akin to the donor’s gut. Inoculation of the gut microbiota with immobilized or planktonic Lactiplantibacillus plantarum NZ3400, a derivative of the probiotic model strain WCFS1, led to successful colonization. Whole-genome sequencing of 45 recovered strains revealed mutations in 16 genes involved in signaling, metabolism, transport, and cell surface. Remarkably, mutations in LP_RS14990, LP_RS15205, and intergenic region LP_RS05100<LP_RS05095 were found in recovered strains from different adaptation experiments. Combined addition of the reference strain NZ3400 and each of those mutants to the gut microbiota resulted in increased abundance of the corresponding mutant in PolyFermS microbiota after 10 days, showing the beneficial nature of these mutations. Our data show that the PolyFermS system is a suitable technology to generate adapted mutants for colonization under colonic conditions. Analysis thereof will provide knowledge about factors involved in gut microbiota colonization and persistence

Parasite genetic distance and local adaptation in co-evolving bacteria-bacteriophage populations

Antagonistic co-evolution between hosts and parasites can lead to local adaptation (LA) such that parasite fitness is greatest in sympatric hosts (or vice versa). The magnitude of LA typically increases with geographical distance, which is assumed to be because genetic (and hence phenotypic) distance increases with geographical distance. Here, we explicitly test the relationships between parasite genetic and phenotypic distance and LA using isolates of co-evolved viral parasites (lytic bacteriophage phi 2) and the host bacterium Pseudomonas fluorescens SBW25. We find positive relationships between parasite genotype and infectivity phenotype, but the strength of the relationship was greater when infectivity was defined by the identity of hosts that could be infected rather than the actual number of hosts infected (host range), and when measurements were compared within rather than among populations. Crucially, we find a monotonic relationship between LA and genetic distance across phage isolates from different populations, although in contrast to many geographical studies, parasite LA decreased with genetic distance. These results can be explained by the fact that bacteria can rapidly adapt to phage infectivity mutations, but that evolved resistance has a degree of specificity to the local phage population. Our results show that antagonistic co-evolution alone can result in predictable links between genetic distance and host-parasite local adaptation

Fitness benefits to bacteria of carrying prophages and prophage‐encoded antibiotic‐resistance genes peak in different environments

Understanding the role of horizontal gene transfer (HGT) in adaptation is a key challenge in evolutionary biology. In microbes, an important mechanism of HGT is prophage acquisition (phage genomes integrated into bacterial chromosomes). Prophages can influence bacterial fitness via transfer of beneficial genes (including antibiotic-resistance genes, ARGs), protection from superinfecting phages, or switching to a lytic lifecycle which releases free phages infectious to competitors. We expect these effects to depend on environmental conditions because of, for example, environment-dependent induction of the lytic lifecycle. However, it remains unclear how costs/benefits of prophages vary across environments. Here, studying prophages with/without ARGs in Escherichia coli, we disentangled effects of prophages alone and adaptive genes they carry. In competition with prophage-free strains, benefits from prophages and ARGs peaked in different environments. Prophages were most beneficial when induction of the lytic lifecycle was common, whereas ARGs were more beneficial upon antibiotic exposure and with reduced prophage induction. Acquisition of prophage-encoded ARGs by competing strains was most common when prophage induction, and therefore free phages, were common. Thus, selection on prophages and adaptive genes they carry varies independently across environments, which is important for predicting the spread of mobile/integrating genetic elements and their role in evolution

Differences in transcription between free-living and CO_2-activated third-stage larvae of Haemonchus contortus

Background: The disease caused by Haemonchus contortus, a blood-feeding nematode of small ruminants, is of major economic importance worldwide. The infective third-stage larva (L3) of this gastric nematode is enclosed in a cuticle (sheath) and, once ingested with herbage by the host, undergoes an exsheathment process that marks the transition from the free-living (L3) to the parasitic (xL3) stage. This study explored changes in gene transcription associated with this transition and predicted, based on comparative analysis, functional roles for key transcripts in the metabolic pathways linked to larval development. Results: Totals of 101,305 (L3) and 105,553 (xL3) expressed sequence tags (ESTs) were determined using 454 sequencing technology, and then assembled and annotated; the most abundant transcripts encoded transthyretin-like, calcium-binding EF-hand, NAD(P)-binding and nucleotide-binding proteins as well as homologues of Ancylostoma-secreted proteins (ASPs). Using an in silico-subtractive analysis, 560 and 685 sequences were shown to be uniquely represented in the L3 and xL3 stages, respectively; the transcripts encoded ribosomal proteins, collagens and elongation factors (in L3), and mainly peptidases and other enzymes of amino acid catabolism (in xL3). Caenorhabditis elegans orthologues of transcripts that were uniquely transcribed in each L3 and xL3 were predicted to interact with a total of 535 other genes, all of which were involved in embryonic development. Conclusion: The present study indicated that some key transcriptional alterations taking place during the transition from the L3 to the xL3 stage of H. contortus involve genes predicted to be linked to the development of neuronal tissue (L3 and xL3), formation of the cuticle (L3) and digestion of host haemoglobin (xL3). Future efforts using next-generation sequencing and bioinformatic technologies should provide the efficiency and depth of coverage required for the determination of the complete transcriptomes of different developmental stages and/or tissues of H. contortus as well as the genome of this important parasitic nematode. Such advances should lead to a significantly improved understanding of the molecular biology of H. contortus and, from an applied perspective, to novel methods of intervention