Detoxification Genes Research Articles

Can colonization by an endophytic fungus transform a plant into a challenging host for insect herbivores?

Endophytic growth of arthropod pathogenic fungi can parasitize insect herbivores without causing damage to the crop. However, studies addressing this tritrophic interaction are absent. Here, the endophytic arthropod pathogenic fungus Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Cordyciptaceae), the polyphagous two-spotted spider mite Tetranychus urticae Koch (Trombidiformes: Tetranychidae), and its preferred plant host Phaseolus vulgaris L. (Fabales: Fabaceae) were selected to study the multi-kingdom interactions among plants, arthropods, and entomopathogenic fungi. Real-Time PCR analysis of nine defense-related genes revealed that a broad range of plant defense mechanisms is activated in response to the endophytic growth of B. bassiana. Moreover, we studied the molecular mechanism adapted by the two-spotted spider mite that underlies resistance. The analysis of 41 detoxification genes revealed that relatively moderate, high, and few numbers of genes were changed in the adults, nymphs, and eggs stages of T. urticae, respectively, after inoculation on colonized tissues of P. vulgaris. The endophytic growth of B. bassiana can have a negative effect on the growth and performance of the pest, in a developmental stage-dependent manner, by priming plant defense pathways. In parallel, the herbivore induces a broad range of detoxification genes that could potentially be involved in adaptation to endophytically colonized plant tissues.

Transcriptome Alterations of an in vitro-Selected, Moderately Resistant, Two-Row Malting Barley in Response to 3ADON, 15ADON, and NIV Chemotypes of Fusarium graminearum.

Fusarium head blight caused by Fusarium graminearum is a devastating disease of malting barley. Mycotoxins associated with contaminated grain can be transferred from malt to beer and pose a health risk to consumers. In western Canada, F. graminearum has undergone an adaptive shift from 15ADON constituency to dominance by virulent 3ADON-producers; likewise, NIV-producers have established in regions of southern United States. Lack of adapted resistance sources with adequate malting quality has promoted the use of alternative breeding methodologies, such as in vitro selection. We studied the low-deoxynivalenol characteristic of in vitro selected, two-row malting barley variety “Norman” by RNAseq in contrast to its parental line “CDC Kendall,” when infected by 15ADON-, 3ADON-, and NIV-producing isolates of F. graminearum. The current study documents higher mycotoxin accumulation by 3ADON isolates, thereby representing increased threat to barley production. At 72–96-h post infection, significant alterations in transcription patterns were observed in both varieties with pronounced upregulation of the phenylpropanoid pathway and detoxification gene categories (UGT, GST, CyP450, and ABC), particularly in 3ADON treatment. Defense response was multitiered, where differential expression in “Norman” associated with antimicrobial peptides (thionin 2.1, defensing, non-specific lipid-transfer protein) and stress-related proteins, such as late embryogenesis abundant proteins, heat-shock, desiccation related, and a peroxidase (HvPrx5). Several gene targets identified in “Norman” would be useful for application of breeding varieties with reduced deoxynivalenol content.

Gene selection for studying frugivore-plant interactions: a review and an example using Queensland fruit fly in tomato.

Fruit production is negatively affected by a wide range of frugivorous insects, among them tephritid fruit flies are one of the most important. As a replacement for pesticide-based controls, enhancing natural fruit resistance through biotechnology approaches is a poorly researched but promising alternative. The use of quantitative reverse transcription PCR (RT-qPCR) is an approach to studying gene expression which has been widely used in studying plant resistance to pathogens and non-frugivorous insect herbivores, and offers a starting point for fruit fly studies. In this paper, we develop a gene selection pipe-line for known induced-defense genes in tomato fruit, Solanum lycopersicum, and putative detoxification genes in Queensland fruit fly, Bactrocera tryoni, as a basis for future RT-qPCR research. The pipeline started with a literature review on plant/herbivore and plant/pathogen molecular interactions. With respect to the fly, this was then followed by the identification of gene families known to be associated with insect resistance to toxins, and then individual genes through reference to annotated B. tryoni transcriptomes and gene identity matching with related species. In contrast for tomato, a much better studied species, individual defense genes could be identified directly through literature research. For B. tryoni, gene selection was then further refined through gene expression studies. Ultimately 28 putative detoxification genes from cytochrome P450 (P450), carboxylesterase (CarE), glutathione S-transferases (GST), and ATP binding cassette transporters (ABC) gene families were identified for B. tryoni, and 15 induced defense genes from receptor-like kinase (RLK), D-mannose/L-galactose, mitogen-activated protein kinase (MAPK), lipoxygenase (LOX), gamma-aminobutyric acid (GABA) pathways and polyphenol oxidase (PPO), proteinase inhibitors (PI) and resistance (R) gene families were identified from tomato fruit. The developed gene selection process for B. tryoni can be applied to other herbivorous and frugivorous insect pests so long as the minimum necessary genomic information, an annotated transcriptome, is available.

Analysis of saponins detoxification genes in Ilyonectria mors-panacis G3B inducing root rot of Panax notoginseng by RNA-Seq

Saponins are kinds of antifungal compounds produced by Panax notoginseng to resist invasion by pathogens. Ilyonectria mors-panacis G3B was the dominant pathogen inducing root rot of P. notoginseng, and the abilities to detoxify saponins were the key to infect P. notoginseng successfully. To research the molecular mechanisms of detoxifying saponins in I. mors-panacis G3B, we used high-throughput RNA-Seq to identify 557 and 1519 differential expression genes (DEGs) in I. mors-panacis G3B with saponins treatments for 4H (Hours) and 12H (Hours) compared with no saponins treatments, respectively. Among these DEGs, we found 93 genes which were simultaneously highly expressed in I. mors-panacis G3B with saponins treatments for 4H and 12H, they mainly belong to genes encoding transporters, glycoside hydrolases, oxidation–reduction enzymes, transcription factors and so on. In addition, there were 21 putative PHI (Pathogen–Host Interaction) genes out of those 93 up-regulated genes. In this report, we analyzed virulence-associated genes in I. mors-panacis G3B which may be related to detoxifying saponins to infect P. notoginseng successfully. They provided an excellent starting point for in-depth study on pathogenicity of I. mors-panacis G3B and developed appropriate root rot disease management strategies in the future.

Identification of yellow gene family and functional analysis of Spodoptera frugiperda yellow-y by CRISPR/Cas9

For a devastating agricultural pest, functional genomics promotes the finding of novel technology to control Spodoptera frugiperda, such as the genetics-based strategies. In the present study, 11 yellow genes were identified in Spodoptera frugiperda. The transcriptome analysis showed the tissue-specific expression of part yellow genes, which suggested the importance of yellow genes in some biological processes in S. frugiperda, such as pigmentation. Among these yellow genes, the expression profiles of yellow-y gene showed that it was expressed in all life stages. In order to realize the further study of yellow-y, we employed CRISPR/Cas9 system to knock out this gene. Following knock out, diverse phenotypes were observed, such as color changes in both larvae and adults. Different from the wild-type larvae and adults, G0 mutants were yellowed since hatching. However, no color difference was observed with the pupal cuticle between the wild-type and mutant pupae before the 8th day. On the basis of the single-pair strategy of G0 generation, the yellow-y gene was proved to be a recessive gene. The G1 yellowish larvae with biallelic mutations displayed a relatively longer development period than wild-type, and often generated abnormal pupae and moths. The deletion of yellow-y also resulted in a decline in the fecundity. The results revealed that yellow-y gene was important for S. frugiperda pigmentation, as well as in its development and reproduction. Besides, the present study set up a standard procedure to knock out genes in S. frugiperda, which could be helpful for our understanding some key molecular processes, such as functional roles of detoxification genes as insecticide resistance mechanisms or modes of action of insecticides to facilitate the management of this insect pest.

Transcriptional response to host chemical cues underpins the expansion of host range in a fungal plant pathogen lineage.

The host range of parasites is an important factor in assessing the dynamics of disease epidemics. The evolution of pathogens to accommodate new hosts may lead to host range expansion, a process the molecular bases of which are largely enigmatic. The fungus Sclerotinia sclerotiorum has been reported to parasitize more than 400 plant species from diverse eudicot families while its close relative, S. trifoliorum, is restricted to plants from the Fabaceae family. We analyzed S. sclerotiorum global transcriptome reprogramming on hosts from six botanical families and reveal a flexible, host-specific transcriptional program. We generated a chromosome-level genome assembly for S. trifoliorum and found near-complete gene space conservation in two representative strains of broad and narrow host range Sclerotinia species. However, S. trifoliorum showed increased sensitivity to the Brassicaceae defense compound camalexin. Comparative analyses revealed a lack of transcriptional response to camalexin in the S. trifoliorum strain and suggest that regulatory variation in detoxification and effector genes at the population level may associate with the genetic accommodation of Brassicaceae in the Sclerotinia host range. Our work proposes transcriptional plasticity and the co-existence of signatures for generalist and polyspecialist adaptive strategies in the genome of a plant pathogen.

Trans-generational effects of copper on nerve damage in Caenorhabditis elegans

The potential toxicity of copper has received great attention for a long time, however, trans-generational effects of copper have not been extensively investigated. Caenorhabditis elegans (C. elegans) was used to evaluate the trans-generational toxicities of copper several physiological endpoints: growth, head thrashes and body bends and degree of neuronal damage. Copper significantly inhibited growth, body bends, head thrashes and caused degeneration of dopaminergic neurons in a concentration-dependent manner in parental worms. Further we found oxidative damage was to underlying the onset of neuron degeneration. In our study copper promoted ROS accumulation, and led to an increased expression of the oxidative stress response-related genes sod-3 and a decreased expression of metal detoxification genes mtl-1 and mtl-2. Moreover, copper increased the fluorescence intensity of the transgenic strain that encodes the antioxidant enzyme SOD-3. Gradually decline in copper-induced impairments were observed in the filial generations without exposure. No growth impairment was shown in F3, the trend of head thrashes recovery gradually appeared in F2 and no growth impairment was shown in F3, the body bends impairment caused by the parental copper exposure was recovery until F4 and no growth impairment was shown in F5. Besides, dopamine neurons revealed damage related to neurobehavioral endpoints, with hereditary effects in the progeny together. In addition, sequencing results suggested that copper exposure could cause epigenetic changes. QRT-PCR results showed that differentially expressed genes can also be passed on to offspring.

Patterns of microbial arsenic detoxification genes in low-arsenic continental paddy soils

Microbes mediate the arsenic detoxification in paddy soils, determining the fate of arsenic in soils and its availability to rice plants, yet little is known about the structures and abundances of functional genes as well as the driving forces in low-arsenic paddy fields. To depict the arsenic detoxification functional gene patterns, 429 soil samples were collected from 39 paddy fields across four climatic zones in China, with the arsenic contents ranged from 9.76 to 19.74 mg kg−1. GeoChip, a microarray-based metagenomic technique, was used to analyze the functional genes involved in arsenic detoxification. A total of three arsenic detoxification gene families were detected, aoxB, arxA (arsenite oxidase), and arsM (methyltransferase). Both the diversity and abundance of functional genes varied significantly among sampling sites (p < 0.05) and decreased along the arsenic gradient. Arsenic detoxification genes were carried by bacteria, archaea, and eukaryotes. Redundancy analysis showed that soil samples were grouped according to both climatic zones they located in and arsenic gradients at the continental scale. Soil pH, average annual temperature (AAT), arsenic, annual average precipitation (AAP), and CEC were the most important factors in shaping the functional structure. Structural equation modeling showed that AAT (r = 0.21), pH (r = −0.20), and arsenic contents (r = −0.11) directly affected the arsenic detoxification gene abundances. These findings provide an overall picture of microbial communities involved in arsenic detoxification in paddy soils and reveal the importance of climatic factors in shaping functional genes across a large spatial scale.

Detoxification gene families in Phylloxera: Endogenous functions and roles in response to the environment

Phylloxera, Daktulosphaira vitifoliae, is an agronomic pest that feeds monophagously on grapevine, Vitis spp. host plants. Phylloxera manipulates primary and secondary plant metabolism to establish either leaf or root galls. We manually annotated 198 detoxification genes potentially involved in plant host manipulation, including cytochrome P450 (66 CYPs), carboxylesterase (20 CCEs), glutathione-S-transferase (10 GSTs), uridine diphosphate-glycosyltransferase (35 UGTs) and ABC transporter (67 ABCs) families. Transcriptomic expression patterns of these detoxification genes were analyzed for root and leaf galls. In addition to these transcriptomic analyses, we reanalyzed recent data from L1 and L2–3 stages feeding on tolerant and resistant rootstock. Data from two agricultural pest aphids, the generalist Myzus persicae and the Fabaceae specialist Acyrthosiphon pisum, and from the true bug vector of Chagas disease, Rhodnius prolixus, were used to perform phylogenetic analyses for each detoxification gene family. We found expansions of several gene sub-families in the genome of D. vitifoliae. Phylogenetically close genes were found to be organized in clusters in the same genomic position and orientation suggesting recent successive duplications. These results highlight the roles of the phylloxera detoxification gene repertoire in insect physiology and in adaptation to plant secondary metabolites, and provide gene candidates for further functional analyses.

Phytochemical Flavone Confers Broad-Spectrum Tolerance to Insecticides in Spodoptera litura by Activating ROS/CncC-Mediated Xenobiotic Detoxification Pathways.

Tolerance to chemical insecticides can be driven by the necessity of herbivorous insects to defend against host plant-produced phytochemicals. However, how the phytochemicals are sensed and further transduced into a defense response associated with insecticide tolerance is poorly understood. Herein, we show that pre-exposure to flavone, a flavonoid phytochemical, effectively enhanced larval tolerance to multiple synthetic insecticides and elevated detoxification enzyme activities in Spodoptera litura. RNA-Seq analysis revealed that flavone induced a spectrum of genes spanning phase I and II detoxification enzyme families, as well as two transcription factors Cap "n" collar isoform C (CncC) and its partner small muscle aponeurosis fibromatosis (MafK). Knocking down of CncC by RNA interference suppressed flavone-induced detoxification gene expression and rendered the larvae more sensitive to the insecticides. Flavone exposure elicited a reactive oxygen species (ROS) burst, while scavenging of ROS inhibited CncC-mediated detoxification gene expression and suppressed flavone-induced detoxification enzyme activation. Metabolome analysis showed that the ingested flavone was mainly converted into three flavonoid metabolites, and only 3-hydroxyflavone was found to affect the ROS/CncC pathway-mediated metabolic detoxification. These results indicate that the ROS/CncC pathway is an important route driving detoxification gene expression responsible for insecticide tolerance after exposure to the phytochemical flavone.

The transcriptome of anal papillae of Aedes aegypti reveals their importance in xenobiotic detoxification and adds significant knowledge on ion, water and ammonia transport mechanisms

The anal papillae of mosquito larvae are osmoregulatory organs in direct contact with the external aquatic environment that actively sequester ions and take up water in dilute freshwater. In the disease vector Aedes aegypti mechanisms of ion, water and ammonia transport have only been partially resolved. Furthermore, A. aegypti larvae are known to reside in high ammonia sewage and high salt brackish waters, and understanding of anal papillae function in these conditions is in its infancy. The objective of this study was to identify the complement of ion and water transport genes expressed by the anal papillae of freshwater larvae by sequencing their transcriptome, and comparing their expression in anal papillae of larvae abruptly transferred to brackish water for 24 h. Results identified a number of ion and water transport proteins, ammonia detoxifying enzymes, a full suite of xenobiotic detoxifying enzymes and transporters, and G-protein coupled receptors of specific hormones. We identified a marked increase in transcript and protein abundance of aquaporin AaAQP2 in the anal papillae with abrupt transfer to brackish water. We present an updated and more comprehensive model for ion and water transport with additional putative transporters for Na+ and Cl- uptake in the anal papillae. These are organs which are actively engaged in Na+, Cl- and water uptake and regulation when the aquatic larvae encounter fluctuating salinities over the course of their development. Furthermore the transcriptome of the anal papillae includes a full set of xenobiotic detoxification genes suggesting that these are important detoxification organs which is particularly important when larvae reside in polluted water.

Permethrin resistance in Aedes aegypti: Genomic variants that confer knockdown resistance, recovery, and death.

Pyrethroids are one of the few classes of insecticides available to control Aedes aegypti, the major vector of dengue, chikungunya, and Zika viruses. Unfortunately, evolving mechanisms of pyrethroid resistance in mosquito populations threaten our ability to control disease outbreaks. Two common pyrethroid resistance mechanisms occur in Ae. aegypti: 1) knockdown resistance, which involves amino acid substitutions at the pyrethroid target site—the voltage-gated sodium channel (VGSC)—and 2) enhanced metabolism by detoxification enzymes. When a heterogeneous population of mosquitoes is exposed to pyrethroids, different responses occur. During exposure, a proportion of mosquitoes exhibit immediate knockdown, whereas others are not knocked-down and are designated knockdown resistant (kdr). When these individuals are removed from the source of insecticide, the knocked-down mosquitoes can either remain in this status and lead to dead or recover within a few hours. The proportion of these phenotypic responses is dependent on the pyrethroid concentration and the genetic background of the population tested. In this study, we sequenced and performed pairwise genome comparisons between kdr, recovered, and dead phenotypes in a pyrethroid-resistant colony from Tapachula, Mexico. We identified single-nucleotide polymorphisms (SNPs) associated with each phenotype and identified genes that are likely associated with the mechanisms of pyrethroid resistance, including detoxification, the cuticle, and insecticide target sites. We identified high association between kdr and mutations at VGSC and moderate association with additional insecticide target site, detoxification, and cuticle protein coding genes. Recovery was associated with cuticle proteins, the voltage-dependent calcium channel, and a different group of detoxification genes. We provide a list of detoxification genes under directional selection in this field-resistant population. Their functional roles in pyrethroid metabolism and their potential uses as genomic markers of resistance require validation.

Acute and chronic toxicity of microcystin-LR and phenanthrene alone or in combination to the cladoceran (Daphnia magna)

Hazardous substances, such as microcystin-LR (MC-LR) and phenanthrene (Phe) are ubiquitous co-contaminants in eutrophic freshwaters, which cause harms to aquatic organisms. However, the risks associated with the co-exposure of aquatic biota to these two chemicals in the environment have received little attention. In this study, the single and mixture toxic effects of MC-LR and Phe mixtures were investigated in Daphnia magna after acute and chronic exposure. Acute tests showed that the median effective concentrations (48 h) for MC-LR, Phe and their mixtures were 13.46, 0.57 and 8.84 mg/L, respectively. Mixture toxicity prediction results indicated that the independent action model was more applicable than the concentration addition model. Moreover, combination index method suggested that the mixture toxicity was concentration dependent. Synergism was elicited at low concentrations of MC-LR and Phe exposure (≤4.04 + 0.17 mg/L), whereas antagonistic or additive effects were induced at higher concentrations. The involved mechanism of antagonism was presumably attributable to the protective effects of detoxification genes activated by high concentrations of MC-LR in mixtures. Additionally, chronic results also showed that exposure to a MC-LR and Phe mixture at low concentrations (≤50 +2 μg/L) resulted in greater toxic effects on D. magna life history than either chemical acting alone. The significant inhibition on detoxification genes and increased accumulation of MC-LR could be accounted for their synergistic toxic effects on D. magna. Our findings revealed the exacerbated ecological hazard of MC-LR and Phe at environmental concentrations (≤50 +2 μg/L), and provided new insights to the potential toxic mechanisms of MC-LR and Phe in aquatic animals.

Resistance in the Genus Spodoptera: Key Insect Detoxification Genes.

Simple SummaryThe moth larvae are among the most damaging pest species on crops worldwide. In this review, we focus on the genus Spodoptera, which can feed on many crops such as rice, cotton or corn. The massive use of insecticides to control these insects has led to the development of resistance. Here, we aim to compare the resistance mechanisms of four species (Spodoptera exigua, Spodoptera frugiperda, Spodoptera littoralis and Spodoptera litura) and highlight the role of enzymes and transporters in resistance to help us understand the molecular basis of their origin.The genus Spodoptera (Lepidoptera: Noctuidae) includes species that are among the most important crop pests in the world. These polyphagous species are able to feed on many plants, including corn, rice and cotton. In addition to their ability to adapt to toxic compounds produced by plants, they have developed resistance to the chemical insecticides used for their control. One of the main mechanisms developed by insects to become resistant involves detoxification enzymes. In this review, we illustrate some examples of the role of major families of detoxification enzymes such as cytochromes P450, carboxyl/cholinesterases, glutathione S-transferases (GST) and transporters such as ATP-binding cassette (ABC) transporters in insecticide resistance. We compare available data for four species, Spodoptera exigua, S. frugiperda, S. littoralis and S. litura. Molecular mechanisms underlying the involvement of these genes in resistance will be described, including the duplication of the CYP9A cluster, over-expression of GST epsilon or point mutations in acetylcholinesterase and ABCC2. This review is not intended to be exhaustive but to highlight the key roles of certain genes.

Analyses of Insecticide Resistance Genes in Aedes aegypti and Aedes albopictus Mosquito Populations from Cameroon.

The emergence of insecticide resistance in Aedes mosquitoes could pose major challenges for arboviral-borne disease control. In this paper, insecticide susceptibility level and resistance mechanisms were assessed in Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) from urban settings of Cameroon. The F1 progeny of Aedes aegypti and Aedes albopictus collected in Douala, Yaoundé and Dschang from August to December 2020 was tested using WHO tube assays with four insecticides: deltamethrin 0.05%, permethrin 0.75%, DDT 4% and bendiocarb 0.1%. TaqMan, qPCR and RT-qPCR assays were used to detect kdr mutations and the expression profiles of eight detoxification genes. Aedes aegypti mosquitoes from Douala were found to be resistant to DDT, permethrin and deltamethrin. Three kdr mutations, F1534C, V1016G and V1016I were detected in Aedes aegypti populations from Douala and Dschang. The kdr allele F1534C was predominant (90%) in Aedes aegypti and was detected for the first time in Aedes albopictus (2.08%). P450s genes, Cyp9J28 (2.23–7.03 folds), Cyp9M6 (1.49–2.59 folds), Cyp9J32 (1.29–3.75 folds) and GSTD4 (1.34–55.3 folds) were found overexpressed in the Douala and Yaoundé Aedes aegypti populations. The emergence of insecticide resistance in Aedes aegypti and Aedes albopictus calls for alternative strategies towards the control and prevention of arboviral vector-borne diseases in Cameroon.

P017 Small bowel transcriptomics define similarities and divergent pathways between Crohn, environmental enteric dysfunction (EED), and celiac diseases, implicating role for the microbiome in the pathogenesis

Abstract Background Crohn disease (CD), environmental enteric dysfunction (EED) and celiac disease are prevalent enteropathies linked to chronic gut inflammation. However, unlike celiac and Crohn that are prevalent in westernized countries, EED is seen in only in low- and middle-income countries of the developing world. Recent work has defined specific EED duodenal microbiota associated with stunting, and transmission of EED histologic changes and weight loss by microbial transfer to germ free mice. Methods We performed high throughput transcriptomics of 94 duodenal samples from the SEEM cohort:52 undernourished EED participants, 17 celiac and 25 healthy North American controls. We compared those to our previously reported transcriptomics of 248 newly diagnosed ileal CD from RISK. Comparison were performed between cases and controls within each cohort. Results Above 90% of the expressed protein coding genes are shared between duodenum samples within SEEM, and Crohn ileal within RISK enabling the anticipated comparison. A substantial number of the down-regulated genes in undernourished EED participants overlapped with celiac (212/481, 44%) and with Crohn Disease (249/481, 52%). Shared reduced signatures and functions included decrease in epithelial lipid metabolism, vitamins, and brush border transport signatures. Relative to celiac disease, suppression of antioxidant and detoxification genes were EED- and Crohn-specific, which include the reduction of metallothioneins (MT family) that buffer against toxic metals, and aldo-keto NADPH- genes (AKR1C family) involved in detoxification of environmental compounds. A smaller proportion of the EED up-regulated signal overlapped with celiac (85/781), and we noted a more significant overlap with Crohn disease (248/781, Chi squares p&amp;lt;0.05). Relative to celiac disease, up-regulation of an innate anti-microbial DUOX2 and LCN2 gene, and of myeloid response signals, several CCL chemokines, and extracellular matrix signature were EED- and Crohn-specific. Consistent with this, greater level of DUOX2 protein was detected in duodenal biopsies from EED subjects vs. celiac and controls and in ileal CD vs. ileal controls. As opposed to the robust dysbiosis previously characterized in Crohn disease, we were unable to identify significant microbial signal in celiac patients in comparison to controls, while recent studies identified microbial patterns linked with EED. Conclusion We highlight important biologic signals widely overlapping between Crohn Disease (CD) and EED transcriptome in the small intestine, suggesting mechanisms involving altered gut microbiota. Inhibiting innate immune activation or reverting Crohn dysbiosis may be beneficial future therapy for Crohn Disease and EED.

The symbiotic relationship between Caenorhabditis elegans and members of its microbiome contributes to worm fitness and lifespan extension

BackgroundA healthy microbiome influences host physiology through a mutualistic relationship, which can be important for the host to cope with cellular stress by promoting fitness and survival. The mammalian microbiome is highly complex and attributing host phenotypes to a specific member of the microbiome can be difficult. The model organism Caenorhabditis elegans and its native microbiome, discovered recently, can serve as a more tractable, experimental model system to study host-microbiome interactions. In this study, we investigated whether certain members of C. elegans native microbiome would offer a benefit to their host and putative molecular mechanisms using a combination of phenotype screening, omics profiling and functional validation.ResultsA total of 16 members of C. elegans microbiome were screened under chemically-induced toxicity. Worms grown with Chryseobacterium sp. CHNTR56 MYb120 or Comamonas sp. 12022 MYb131, were most resistant to oxidative chemical stress (SiO2 nanoparticles and juglone), as measured by progeny output. Further investigation showed that Chryseobacterium sp. CHNTR56 positively influenced the worm’s lifespan, whereas the combination of both isolates had a synergistic effect. RNAseq analysis of young adult worms, grown with either isolate, revealed the enrichment of cellular detoxification mechanisms (glutathione metabolism, drug metabolism and metabolism of xenobiotics) and signaling pathways (TGF-beta and Wnt signaling pathways). Upregulation of cysteine synthases (cysl genes) in the worms, associated with glutathione metabolism, was also observed. Nanopore sequencing uncovered that the genomes of the two isolates have evolved to favor the specific route of the de novo synthesis pathway of vitamin B6 (cofactor of cysl enzymes) through serC or pdxA2 homologs. Finally, co-culture with vitamin B6 extended worm lifespan.ConclusionsIn summary, our study indicates that certain colonizing members of C. elegans have genomic diversity in vitamin B6 synthesis and promote host fitness and lifespan extension. The regulation of host cellular detoxification genes (i.e. gst) along with cysl genes at the transcriptome level and the bacterium-specific vitamin B6 synthesis mechanism at the genome level are in an agreement with enhanced host glutathione-based cellular detoxification due to this interspecies relationship. C. elegans is therefore a promising alternative model to study host-microbiome interactions in host fitness and lifespan.

Rice recruits Sphingomonas strain HJY-rfp via root exudate regulation to increase chlorpyrifos tolerance and boost residual catabolism.

Inoculation with pollution-degrading endophytes boosts the catabolism of residual contaminants and promotes the pollution adaptation of host plants. We investigated the interaction pattern between Sphingomonas strain HJY-rfp, a chlorpyrifos-degrading endophytic bacterium, and rice (Oryza sativa) under pesticide stress using hydroponic cultivation. We observed a notable trend of endophytic root colonization in rice plants treated with 10 mg l-1 chlorpyrifos solution, and after 24 h the migration of HJY-rfp enhanced the chlorpyrifos degradation rate in leaves and stems by 53.36% and 40.81%, respectively. Critically, the rice root exudate profile (organic acids and amino acids) changed under chlorpyrifos stress, and variations in the contents of several components affected the chemotactic behaviour of HJY-rfp. HJY-rfp colonization dramatically activated defensive enzymes, which enabled efficient scavenging of reactive oxygen species, and led to 9.8%, 22.5%, and 41.9% increases in shoot length, fresh weight, and accumulation of total chlorophyll, respectively, in rice suffering from oxidative damage by chlorpyrifos. Endophytic colonization caused up-regulation of detoxification genes that have shown a significant positive correlation with chlorpyrifos degradation in vivo. Collectively, our results demonstrate that agrochemical stress causes plants to actively recruit specific symbiotic microbes to detoxify contaminants and survive better under pollution conditions.

Insecticide resistance status and mechanisms in Aedes aegypti populations from Senegal.

Aedes aegypti is the main epidemic vector of arboviruses in Africa. In Senegal, control activities are mainly limited to mitigation of epidemics, with limited information available for Ae. aegypti populations. A better understanding of the current Ae. aegypti susceptibility status to various insecticides and relevant resistance mechanisms involved is needed for the implementation of effective vector control strategies. The present study focuses on the detection of insecticide resistance and reveals the related mechanisms in Ae. aegypti populations from Senegal.Bioassays were performed on Ae. aegypti adults from nine Senegalese localities (Matam, Louga, Barkedji, Ziguinchor, Mbour, Fatick, Dakar, Kédougou and Touba). Mosquitoes were exposed to four classes of insecticides using the standard WHO protocols. Resistance mechanisms were investigated by genotyping for pyrethroid target site resistance mutations (V1016G, V1016I, F1534C and S989P) and measuring gene expression levels of key detoxification genes (CYP6BB2, CYP9J26, CYP9J28, CYP9J32, CYP9M6, CCEae3a and GSTD4).All collected populations were resistant to DDT and carbamates except for the ones in Matam (Northern region). Resistance to permethrin was uniformly detected in mosquitoes from all areas. Except for Barkédji and Touba, all populations were characterized by a susceptibility to 0.75% Permethrin. Susceptibility to type II pyrethroids was detected only in the Southern regions (Kédougou and Ziguinchor). All mosquito populations were susceptible to 5% Malathion, but only Kédougou and Matam mosquitoes were susceptible to 0.8% Malathion. All populations were resistant to 0.05% Pirimiphos-methyl, whereas those from Louga, Mbour and Barkédji, also exhibited resistance to 1% Fenitrothion. None of the known target site pyrethroid resistance mutations was present in the mosquito samples included in the genotyping analysis (performed in > 1500 samples). In contrast, a remarkably high (20-70-fold) overexpression of major detoxification genes was observed, suggesting that insecticide resistance is mostly mediated through metabolic mechanisms. These data provide important evidence to support dengue vector control in Senegal.

The Role of NRF2/KEAP1 Signaling Pathway in Cancer Metabolism.

The nuclear factor-erythroid 2 p45-related factor 2 (NRF2, also called Nfe2l2) and its cytoplasmic repressor, Kelch-like ECH-associated protein 1 (KEAP1), are major regulators of redox homeostasis controlling a multiple of genes for detoxification and cytoprotective enzymes. The NRF2/KEAP1 pathway is a fundamental signaling cascade responsible for the resistance of metabolic, oxidative stress, inflammation, and anticancer effects. Interestingly, a recent accumulation of evidence has indicated that NRF2 exhibits an aberrant activation in cancer. Evidence has shown that the NRF2/KEAP1 signaling pathway is associated with the proliferation of cancer cells and tumerigenesis through metabolic reprogramming. In this review, we provide an overview of the regulatory molecular mechanism of the NRF2/KEAP1 pathway against metabolic reprogramming in cancer, suggesting that the regulation of NRF2/KEAP1 axis might approach as a novel therapeutic strategy for cancers.