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1.
Mol Plant Microbe Interact ; 32(8): 972-985, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31204904

RESUMO

The rhizobium-legume symbiotic system is crucial for nitrogen cycle balance in agriculture. Hydrogen sulfide (H2S), a gaseous signaling molecule, may regulate various physiological processes in plants. However, whether H2S has regulatory effect in this symbiotic system remains unknown. Herein, we investigated the possible role of H2S in the symbiosis between soybean (Glycine max) and rhizobium (Sinorhizobium fredii). Our results demonstrated that an exogenous H2S donor (sodium hydrosulfide [NaHS]) treatment promoted soybean growth, nodulation, and nitrogenase (Nase) activity. Western blotting analysis revealed that the abundance of Nase component nifH was increased by NaHS treatment in nodules. Quantitative real-time polymerase chain reaction data showed that NaHS treatment upregulated the expressions of symbiosis-related genes nodA, nodC, and nodD of S. fredii. In addition, expression of soybean nodulation marker genes, including early nodulin 40 (GmENOD40), ERF required for nodulation (GmERN), nodulation signaling pathway 2b (GmNSP2b), and nodulation inception genes (GmNIN1a, GmNIN2a, and GmNIN2b), were upregulated. Moreover, the expressions of glutamate synthase (GmGOGAT), asparagine synthase (GmAS), nitrite reductase (GmNiR), ammonia transporter (GmSAT1), leghemoglobin (GmLb), and nifH involved in nitrogen metabolism were upregulated in NaHS-treated soybean roots and nodules. Together, our results suggested that H2S may act as a positive signaling molecule in the soybean-rhizobia symbiotic system and enhance the system's nitrogen fixation ability.


Assuntos
Sulfeto de Hidrogênio , Fixação de Nitrogênio , Nodulação , Rhizobium , Soja , Gasotransmissores/farmacologia , Sulfeto de Hidrogênio/farmacologia , Fixação de Nitrogênio/efeitos dos fármacos , Nodulação/efeitos dos fármacos , Rhizobium/fisiologia , Soja/microbiologia , Simbiose/efeitos dos fármacos
2.
PLoS Negl Trop Dis ; 13(2): e0007159, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30818326

RESUMO

There is a significant need for improved treatments for onchocerciasis and lymphatic filariasis, diseases caused by filarial worm infection. In particular, an agent able to selectively kill adult worms (macrofilaricide) would be expected to substantially augment the benefits of mass drug administration (MDA) with current microfilaricides, and to provide a solution to treatment of onchocerciasis / loiasis co-infection, where MDA is restricted. We have identified a novel macrofilaricidal agent, Tylosin A (TylA), which acts by targeting the worm-symbiont Wolbachia bacterium. Chemical modification of TylA leads to improvements in anti-Wolbachia activity and oral pharmacokinetic properties; an optimized analog (ABBV-4083) has been selected for clinical evaluation.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas , Filaricidas/farmacologia , Tilosina/análogos & derivados , Tilosina/farmacologia , Wolbachia/efeitos dos fármacos , Animais , Antibacterianos/farmacocinética , Filariose Linfática/tratamento farmacológico , Feminino , Filaricidas/farmacocinética , Filarioidea/efeitos dos fármacos , Filarioidea/microbiologia , Gerbillinae , Camundongos , Camundongos Endogâmicos BALB C , Oncocercose/tratamento farmacológico , Simbiose/efeitos dos fármacos
3.
Fish Shellfish Immunol ; 88: 540-545, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30885744

RESUMO

Intestinal bacteria play an important role in the health and provide a variety of beneficial effects to host. Immunosuppressant can reduce the immunity of host and increase the susceptibility to pathogens. But it is not clear whether the increased susceptibility caused by immunosuppressant is related to changes of gut microbiota. In this study, we used crucian carp administrated with dexamethasone to explore the effects of immunosuppressants on gut microbial communities and further evaluate the potential association between changes in gut microbiota and susceptibility to pathogens. The results of MANOVA based on the top 10 PCoA axis scores from unweighed/weighted UniFrac distances showed that administration of dexamethasone (P = 0.021) and the administration time (P = 0.027) had a significant impact on the gut microbial composition, regardless of pathogens infection status (P = 0.35). After administration with dexamethasone, the fish had higher abundance of Cetobacterium and lower abundance of Bacillus and Lactococcus, and the abundance of genus Bacillus, Pseudomonas and Lactococcus decreased along with prolong administration time of dexamethasone. The results may help us understand the correlation between the host susceptibility to pathogenic bacteria and gut microbial community shift, and extend our knowledge regarding the role of gut microbiota in keeping the balance between pathogenic and symbiotic bacteria.


Assuntos
Bactérias/efeitos dos fármacos , Carpas/imunologia , Suscetibilidade a Doenças/microbiologia , Microbioma Gastrointestinal , Imunossupressão/efeitos adversos , Animais , Anti-Inflamatórios/efeitos adversos , Bactérias/isolamento & purificação , Carpas/microbiologia , Dexametasona/efeitos adversos , Imunossupressores/efeitos adversos , Intestinos/imunologia , Intestinos/microbiologia , Simbiose/efeitos dos fármacos
4.
Sci Total Environ ; 656: 1346-1357, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30625663

RESUMO

Legume-rhizobial symbiosis plays an important role in agriculture and ecological restoration. However, knowledge of the molecular mechanisms, especially the microstructure and global transcriptional profiling, of the symbiosis process under heavy metal contamination is limited. In this study, a heavy metal-tolerant legume, Medicago lupulina, was treated with different concentrations of copper (Cu). The results showed that the early infection process was inhibited and the nodule ultrastructure was changed under 200 mg kg-1 Cu stress. Most infection threads (ITs) were prevented from entering the nodule cells, and few rhizobia were released into the host cells, in which thickening of the plant cell wall and IT wall was observed, demonstrating that rhizobial invasion was inhibited under Cu stress. RNA-seq analysis indicated that a strong shift in gene expression occurred (3257 differentially expressed genes, DEGs). The most pronounced effect was the upregulation of a set of 71 of 73 DEGs for nodule-specific cysteine-rich peptides, which have been shown to control the terminal differentiation of rhizobia in the nodules and to have antimicrobial activity. Various genes for metal transport, chelation binding and antioxidant defence were regulated. In particular, the DEGs for Cu trafficking and detoxification were induced during nodule formation. The DEGs for ethylene (ET) biosynthesis and signalling were also differentially expressed during nodulation, suggesting that the inhibition of nodulation by Cu occurred partially through ET signalling. Furthermore, the genes related to the cell wall were mostly upregulated and most likely involved in cell wall thickening. These findings provide an integrated understanding of the effects of Cu on legume nodule symbiosis at the molecular and phenotypic levels.


Assuntos
Cobre/efeitos adversos , Medicago/efeitos dos fármacos , Bactérias Fixadoras de Nitrogênio/fisiologia , Fenótipo , Poluentes do Solo/efeitos adversos , Simbiose/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Medicago/genética , Medicago/fisiologia , Medicago/ultraestrutura , Microscopia Eletrônica de Transmissão , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nódulos Radiculares de Plantas/efeitos dos fármacos , Nódulos Radiculares de Plantas/microbiologia , Nódulos Radiculares de Plantas/fisiologia , Nódulos Radiculares de Plantas/ultraestrutura
5.
Proc Natl Acad Sci U S A ; 116(1): 233-238, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30559205

RESUMO

The composition of the gut microbiota is largely determined by environmental factors including the host diet. Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron Silencing by fructose and glucose requires the 5' leader region of the mRNA specifying the protein, designated Roc for regulator of colonization. Incorporation of the roc leader mRNA in front of a heterologous gene was sufficient for fructose and glucose to turn off expression of the corresponding protein. An engineered strain refractory to Roc silencing by these sugars outcompeted wild-type B. thetaiotaomicron in mice fed a diet rich in glucose and sucrose (a disaccharide composed of glucose and fructose), but not in mice fed a complex polysaccharide-rich diet. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Bacteroides thetaiotaomicron/efeitos dos fármacos , Carboidratos da Dieta/farmacologia , Açúcares da Dieta/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Proteínas de Bactérias/metabolismo , Frutose/administração & dosagem , Frutose/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Glucose/administração & dosagem , Glucose/farmacologia , Camundongos , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Simbiose/efeitos dos fármacos
6.
PLoS Comput Biol ; 14(6): e1006179, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29927925

RESUMO

Polymicrobial interactions play an important role in shaping the outcome of antibiotic treatment, yet how multispecies communities respond to antibiotic assault is still little understood. Here we use an individual-based simulation model of microbial biofilms to investigate how competitive and mutualistic interactions between an antibiotic-resistant and a susceptible strain (or species) influence the two-lineage community response to antibiotic exposure. Our model predicts that while increasing competition and antibiotics leads to increasing competitive release of the antibiotic-resistant strain, hitting a mutualistic community of cross-feeding species with antibiotics leads to a mutualistic suppression effect where both susceptible and resistant species are harmed. We next show that the impact of antibiotics is further governed by emergent spatial feedbacks within communities. Mutualistic cross-feeding communities can rescue susceptible members by subsidizing their growth inside the biofilm despite lack of access to the nutrient-rich and high-antibiotic growing front. Moreover, we show that antibiotic detoxification by resistant cells can protect nearby susceptible cells, but such cross-protection is more effective in mutualistic communities because mutualism drives mixing of resistant and susceptible cells. In contrast, competition leads to segregation, which ultimately prevents susceptible cells to profit from detoxification. Understanding how the interplay between microbial metabolic interactions and community spatial structuring shapes the outcome of antibiotic treatment can be key to effectively leverage the power of antibiotics and promote microbiome health.


Assuntos
Antibacterianos/farmacologia , Bactérias , Infecções Bacterianas/microbiologia , Interações Microbianas , Modelos Biológicos , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Infecções Bacterianas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Biologia Computacional , Farmacorresistência Bacteriana , Humanos , Interações Microbianas/efeitos dos fármacos , Interações Microbianas/fisiologia , Simbiose/efeitos dos fármacos , Simbiose/fisiologia
7.
Environ Pollut ; 241: 607-615, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29886381

RESUMO

Multiple contaminants can affect plant-microbial remediation processes because of their interactive effects on environmental behaviour, bioavailability and plant growth. Recent studies have suggested that arbuscular mycorrhizal fungi (AMF) can facilitate the revegetation of soils co-contaminated with rare earth elements (REEs) and heavy metals. However, little is known regarding the role of AMF in the interaction of REEs and heavy metals. A pot experiment was conducted to evaluate the effects of Claroideoglomus etunicatum on the biomass, nutrient uptake, metal uptake and translocation of maize grown in soils spiked with Lanthanum (La) and Cadmium (Cd). The results indicated that individual and combined applications of La (100 mg kg-1) and Cd (5 mg kg-1) significantly decreased root colonization rates by 22.0%-35.0%. With AMF inoculation, dual-metal treatment significantly increased maize biomass by 26.2% compared to single-metal treatment. Dual-metal treatment significantly increased N, P and K uptake by 20.1%-76.8% compared to single-metal treatment. Dual-metal treatment significantly decreased shoot La concentration by 52.9% compared to single La treatment, whereas AM symbiosis caused a greater decrease of 87.8%. Dual-metal treatment significantly increased shoot and root Cd concentrations by 65.5% and 58.7% compared to single Cd treatment and the La translocation rate by 142.0% compared to single La treatment, whereas no difference was observed between their corresponding treatments with AMF inoculation. Furthermore, AMF had differential effects on the interaction of La and Cd on metal uptake and translocation under the background concentrations of soil metals. Taken together, these results indicated that AMF significantly affected the interaction between La and Cd, depending on metal types and concentrations in soils. These findings promote a further understanding of the contributions of AMF to the phytoremediation of co-contaminated soil.


Assuntos
Cádmio/análise , Lantânio/análise , Micorrizas/efeitos dos fármacos , Poluentes do Solo/toxicidade , Zea mays/microbiologia , Biodegradação Ambiental , Biomassa , Cádmio/toxicidade , Glomeromycota , Lantânio/toxicidade , Metais Pesados/análise , Micorrizas/química , Micorrizas/fisiologia , Desenvolvimento Vegetal , Raízes de Plantas/efeitos dos fármacos , Plântula/química , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise , Simbiose/efeitos dos fármacos , Zea mays/crescimento & desenvolvimento
8.
Nat Commun ; 9(1): 1383, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29643375

RESUMO

Understanding the mechanisms that promote cooperative behaviors of bacteria in their hosts is of great significance to clinical therapies. Environmental stress is generally believed to increase competition and reduce cooperation in bacteria. Here, we show that bacterial cooperation can in fact be maintained because of environmental stress. We show that Pseudomonas aeruginosa regulates the secretion of iron-scavenging siderophores in the presence of different environmental stresses, reserving this public good for private use in protection against reactive oxygen species when under stress. We term this strategy "conditional privatization". Using a combination of experimental evolution and theoretical modeling, we demonstrate that in the presence of environmental stress the conditional privatization strategy is resistant to invasion by non-producing cheaters. These findings show how the regulation of public goods secretion under stress affects the evolutionary stability of cooperation in a pathogenic population, which may assist in the rational development of novel therapies.


Assuntos
Antibiose/fisiologia , Ferro/metabolismo , Oligopeptídeos/biossíntese , Pseudomonas aeruginosa/fisiologia , Sideróforos/biossíntese , Simbiose/fisiologia , Antibacterianos/farmacologia , Antibiose/efeitos dos fármacos , Antibiose/efeitos da radiação , Evolução Biológica , Contagem de Colônia Microbiana , Fluoresceínas/química , Corantes Fluorescentes/química , Oligopeptídeos/metabolismo , Fótons/efeitos adversos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Sideróforos/metabolismo , Estresse Fisiológico , Simbiose/efeitos dos fármacos , Simbiose/efeitos da radiação , Tobramicina/farmacologia
9.
Can J Microbiol ; 64(8): 511-526, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29620430

RESUMO

Aluminum (Al) toxicity is a major problem affecting soil fertility, microbial diversity, and nutrient uptake of plants. Rhizobia response and legume interaction under Al conditions are still unknown; it is important to understand how to develop and improve legume cultivation under Al stress. In this study, rhizobia response was recorded under different Al concentrations. Al effect on rhizobial cells was characterized by combination with different two pH conditions. Symbiosis process was compared between α- and ß-rhizobia inoculated onto soybean varieties. Rhizobial cell numbers was decreased as Al concentration increased. However, induced Al tolerance considerably depended on rhizobia types and their origins. Accordingly, organic acid results were in correlation with growth rate and cell density which suggested that citric acid might be a positive selective force for Al tolerance and plant interaction on rhizobia. Al toxicity delayed and interrupted the plant-rhizobia interaction and the effect was more pronounced under acidic conditions. Burkholderia fungorum VTr35 significantly improved plant growth under acid-Al stress in combination with all soybean varieties. Moreover, plant genotype was an important factor to establish an effective nodulation and nitrogen fixation under Al stress. Additionally, tolerant rhizobia could be applied as an inoculant on stressful agroecosystems. Furthermore, metabolic pathways have still been unknown under Al stress.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Alumínio/toxicidade , Rhizobium/fisiologia , Soja/microbiologia , Simbiose/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Fixação de Nitrogênio/efeitos dos fármacos , Nodulação/efeitos dos fármacos , Rhizobium/efeitos dos fármacos , Rhizobium/genética , Solo/química , Microbiologia do Solo , Soja/genética , Soja/fisiologia
10.
Proc Natl Acad Sci U S A ; 115(17): 4447-4452, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29632193

RESUMO

Animal-microbe mutualisms are typically maintained by vertical symbiont transmission or partner choice. A third mechanism, screening of high-quality symbionts, has been predicted in theory, but empirical examples are rare. Here we demonstrate that ambrosia beetles rely on ethanol within host trees for promoting gardens of their fungal symbiont and producing offspring. Ethanol has long been known as the main attractant for many of these fungus-farming beetles as they select host trees in which they excavate tunnels and cultivate fungal gardens. More than 300 attacks by Xylosandrus germanus and other species were triggered by baiting trees with ethanol lures, but none of the foundresses established fungal gardens or produced broods unless tree tissues contained in vivo ethanol resulting from irrigation with ethanol solutions. More X. germanus brood were also produced in a rearing substrate containing ethanol. These benefits are a result of increased food supply via the positive effects of ethanol on food-fungus biomass. Selected Ambrosiella and Raffaelea fungal isolates from ethanol-responsive ambrosia beetles profited directly and indirectly by (i) a higher biomass on medium containing ethanol, (ii) strong alcohol dehydrogenase enzymatic activity, and (iii) a competitive advantage over weedy fungal garden competitors (Aspergillus, Penicillium) that are inhibited by ethanol. As ambrosia fungi both detoxify and produce ethanol, they may maintain the selectivity of their alcohol-rich habitat for their own purpose and that of other ethanol-resistant/producing microbes. This resembles biological screening of beneficial symbionts and a potentially widespread, unstudied benefit of alcohol-producing symbionts (e.g., yeasts) in other microbial symbioses.


Assuntos
Aspergillus/fisiologia , Besouros/microbiologia , Etanol/farmacologia , Penicillium/fisiologia , Simbiose/efeitos dos fármacos , Animais , Etanol/metabolismo , Simbiose/fisiologia
11.
Biomed Res Int ; 2018: 8031213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29662899

RESUMO

Most legume species have the ability to establish a symbiotic relationship with soil nitrogen-fixing rhizobacteria that promote plant growth and productivity. There is an increasing evidence of reactive oxygen species (ROS) important role in formation of legume-rhizobium symbiosis and nodule functioning. Environmental pollutants such as chromium compounds can cause damage to rhizobia, legumes, and their symbiosis. In plants, toxic effects of chromium(VI) compounds are associated with the increased production of ROS and oxidative stress development as well as with inhibition of pigment synthesis and modification of virtually all cellular components. These metabolic changes result in inhibition of seed germination and seedling development as well as reduction of plant biomass and crop yield. However, if plants establish symbiosis with rhizobia, heavy metals are accumulated preferentially in nodules decreasing the toxicity of metals to the host plant. This review summarizes data on toxic effects of chromium on legume plants and legume-rhizobium symbiosis. In addition, we discussed the role of oxidative stress in both chromium toxicity and formation of rhizobial symbiosis and use of nodule bacteria for minimizing toxic effects of chromium on plants.


Assuntos
Cromo/toxicidade , Fabaceae/metabolismo , Rhizobium/fisiologia , Simbiose , Fabaceae/efeitos dos fármacos , Radicais Livres/metabolismo , Rhizobium/efeitos dos fármacos , Simbiose/efeitos dos fármacos
12.
Nature ; 555(7698): 623-628, 2018 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-29555994

RESUMO

A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.


Assuntos
Bactérias/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Antibacterianos/farmacologia , Antipsicóticos/farmacologia , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Estudos de Coortes , Ensaios de Triagem em Larga Escala , Humanos , Técnicas In Vitro , Viabilidade Microbiana/efeitos dos fármacos , Reprodutibilidade dos Testes , Simbiose/efeitos dos fármacos
13.
Microb Pathog ; 114: 420-430, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29191709

RESUMO

Strigolactones (SLs) play an important role in controlling root growth, shoot branching, and plant-symbionts interaction. Despite the importance, the components of SL biosynthesis and signaling have not been unequivocally explored in soybean. Here we identified the putative components of SL synthesis enzymes GmMAX1a and GmMAX4a with tissue expression patterns and were apparently regulated by rhizobia infection and changed during nodule development. GmMAX1a and GmMAX4a were further characterized in soybean nodulation with knockdown transgenic hairy roots. GmMAX1a and GmMAX4a knockdown lines exhibit decreased nodule number and expression levels of several nodulation genes required for nodule development. Hormone analysis showed that GmMAX1a and GmMAX4a knockdown hairy roots had increased physiological level of ABA and JA but significantly decreased auxin content. This study not only revealed the conservation of SL biosynthesis but also showed close interactions between SL and other hormone signaling in controlling plant development and legume-rhizobia interaction.


Assuntos
Reguladores de Crescimento de Planta/farmacologia , Nodulação/efeitos dos fármacos , Rhizobium/efeitos dos fármacos , Soja/metabolismo , Simbiose/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Genes de Plantas , Vetores Genéticos , Oxigenases/genética , Oxigenases/farmacologia , Reguladores de Crescimento de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Transdução de Sinais , Soja/genética , Soja/crescimento & desenvolvimento , Soja/microbiologia
14.
Yonsei Med J ; 59(1): 4-12, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29214770

RESUMO

The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.


Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Disbiose/microbiologia , Humanos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Simbiose/efeitos dos fármacos
15.
Aquat Toxicol ; 194: 132-139, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29179148

RESUMO

Heavy metals have become one of the main pollutants in the marine environment and a major threat to the growth and reproduction of stony corals. In the present study, the density of symbiotic zooxanthellae, levels of crucial physiological activities and the transcriptome were investigated in the stony coral Pocillopora damicornis after the acute exposure to elevated cadmium concentration. The density of symbiotic zooxanthellae decreased significantly during 12-24h period, and reached lowest at 24h after acute cadmium stress. No significant changes were observed in the activity of glutathione S-transferase during the entire stress exposure. The activities of superoxide dismutase and catalase, and the concentration of glutathione decreased significantly, but the activation level of caspase3 increased significantly after cadmium exposure. Furthermore, transcriptome sequencing and bioinformatics analysis revealed 3538 significantly upregulated genes and 8048 significantly downregulated genes at 12h after the treatment. There were 12 overrepresented GO terms for significantly upregulated genes, mostly related to unfolded protein response, endoplasmic reticulum stress and apoptosis. In addition, a total of 32 GO terms were overrepresented for significantly downregulated genes, and mainly correlated with macromolecular metabolic processes. These results collectively suggest that acute cadmium stress could induce apoptosis by repressing the production of the antioxidants, elevating oxidative stress and activating the unfolded protein response. This cascade of reactions would result to the collapse of the coral-zooxanthella symbiosis and the expulsion of symbiotic zooxanthellae in the stony coral P. damicornis, ultimately leading to coral bleaching.


Assuntos
Antozoários/efeitos dos fármacos , Cádmio/toxicidade , Dinoflagelados/efeitos dos fármacos , Simbiose/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Antozoários/genética , Antozoários/fisiologia , China , Dinoflagelados/fisiologia , Transcriptoma/efeitos dos fármacos
16.
J Neurosci ; 37(48): 11758-11768, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29089436

RESUMO

Peripheral pain signaling reflects a balance of pronociceptive and antinociceptive influences; the contribution by the gastrointestinal microbiota to this balance has received little attention. Disorders, such as inflammatory bowel disease and irritable bowel syndrome, are associated with exaggerated visceral nociceptive actions that may involve altered microbial signaling, particularly given the evidence for bacterial dysbiosis. Thus, we tested whether a community of commensal gastrointestinal bacteria derived from a healthy human donor (microbial ecosystem therapeutics; MET-1) can affect the excitability of male mouse DRG neurons. MET-1 reduced the excitability of DRG neurons by significantly increasing rheobase, decreasing responses to capsaicin (2 µm) and reducing action potential discharge from colonic afferent nerves. The increase in rheobase was accompanied by an increase in the amplitude of voltage-gated K+ currents. A mixture of bacterial protease inhibitors abrogated the effect of MET-1 effects on DRG neuron rheobase. A serine protease inhibitor but not inhibitors of cysteine proteases, acid proteases, metalloproteases, or aminopeptidases abolished the effects of MET-1. The serine protease cathepsin G recapitulated the effects of MET-1 on DRG neurons. Inhibition of protease-activated receptor-4 (PAR-4), but not PAR-2, blocked the effects of MET-1. Furthermore, Faecalibacterium prausnitzii recapitulated the effects of MET-1 on excitability of DRG neurons. We conclude that serine proteases derived from commensal bacteria can directly impact the excitability of DRG neurons, through PAR-4 activation. The ability of microbiota-neuronal interactions to modulate afferent signaling suggests that therapies that induce or correct microbial dysbiosis may impact visceral pain.SIGNIFICANCE STATEMENT Commercially available probiotics have the potential to modify visceral pain. Here we show that secretory products from gastrointestinal microbiota derived from a human donor signal to DRG neurons. Their secretory products contain serine proteases that suppress excitability via activation of protease-activated receptor-4. Moreover, from this community of commensal microbes, Faecalibacterium prausnitzii strain 16-6-I 40 fastidious anaerobe agar had the greatest effect. Our study suggests that therapies that induce or correct microbial dysbiosis may affect the excitability of primary afferent neurons, many of which are nociceptive. Furthermore, identification of the bacterial strains capable of suppressing sensory neuron excitability, and their mechanisms of action, may allow therapeutic relief for patients with gastrointestinal diseases associated with pain.


Assuntos
Gânglios Espinais/enzimologia , Microbioma Gastrointestinal/fisiologia , Granzimas/administração & dosagem , Neurônios/enzimologia , Simbiose/fisiologia , Animais , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/microbiologia , Peptídeo Hidrolases/administração & dosagem , Simbiose/efeitos dos fármacos
17.
Mar Pollut Bull ; 124(2): 687-693, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-28865792

RESUMO

We examined the effect of two herbicides (Irgarol 1051 and Diuron) on symbiotic dinoflagellates in the hard coral Acropora digitifera using delayed fluorescence (DF), specifically assessing changes in molecular membrane transport, i.e. inflow and outflow rates, and the binding of the herbicides to target proteins in photosystem II. The DF approach is rapid (e.g. measurement time, 60 s) and non-invasive, and can provide data on the extent of a photosynthetic system and the activity of its electron carriers. The DF of A. digitifera is inhibited 2 h after exposure to 1 µg/L of either Irgarol or Diuron. Analysis of DF inhibition over time by a compartment model suggests that Irgarol exposure results in a relatively higher inflow rate and lower outflow rate than does Diuron exposure. This suggests that Irgarol exposure more strongly inhibits photosynthesis and that the coral symbiotic dinoflagellates recover less from inhibition.


Assuntos
Antozoários/efeitos dos fármacos , Dinoflagelados/efeitos dos fármacos , Exposição Ambiental , Monitoramento Ambiental/métodos , Fluorescência , Poluentes Químicos da Água/toxicidade , Animais , Antozoários/fisiologia , Dinoflagelados/fisiologia , Diurona/toxicidade , Herbicidas/toxicidade , Simbiose/efeitos dos fármacos , Triazinas/toxicidade
18.
Nature ; 548(7665): 43-51, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28770836

RESUMO

The human body carries vast communities of microbes that provide many benefits. Our microbiome is complex and challenging to understand, but evolutionary theory provides a universal framework with which to analyse its biology and health impacts. Here we argue that to understand a given microbiome feature, such as colonization resistance, host nutrition or immune development, we must consider how hosts and symbionts evolve. Symbionts commonly evolve to compete within the host ecosystem, while hosts evolve to keep the ecosystem on a leash. We suggest that the health benefits of the microbiome should be understood, and studied, as an interplay between microbial competition and host control.


Assuntos
Evolução Biológica , Ecossistema , Interações Microbianas/fisiologia , Microbiota/fisiologia , Modelos Biológicos , Simbiose/fisiologia , Animais , Biodiversidade , Saúde , Humanos , Interações Microbianas/efeitos dos fármacos , Interações Microbianas/imunologia , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Especificidade da Espécie , Simbiose/efeitos dos fármacos , Simbiose/imunologia
19.
Plant Physiol ; 175(1): 529-542, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28751316

RESUMO

Strigolactones (SLs) influence the ability of legumes to associate with nitrogen-fixing bacteria. In this study, we determine the precise stage at which SLs influence nodulation. We show that SLs promote infection thread formation, as a null SL-deficient pea (Pisum sativum) mutant forms significantly fewer infection threads than wild-type plants, and this reduction can be overcome by the application of the synthetic SL GR24. We found no evidence that SLs influence physical events in the plant before or after infection thread formation, since SL-deficient plants displayed a similar ability to induce root hair curling in response to rhizobia or Nod lipochitooligosaccharides (LCOs) and SL-deficient nodules appear to fix nitrogen at a similar rate to those of wild-type plants. In contrast, an SL receptor mutant displayed no decrease in infection thread formation or nodule number, suggesting that SL deficiency may influence the bacterial partner. We found that this influence of SL deficiency was not due to altered flavonoid exudation or the ability of root exudates to stimulate bacterial growth. The influence of SL deficiency on infection thread formation was accompanied by reduced expression of some early nodulation genes. Importantly, SL synthesis is down-regulated by mutations in genes of the Nod LCO signaling pathway, and this requires the downstream transcription factor NSP2 but not NIN This, together with the fact that the expression of certain SL biosynthesis genes can be elevated in response to rhizobia/Nod LCOs, suggests that Nod LCOs may induce SL biosynthesis. SLs appear to influence nodulation independently of ethylene action, as SL-deficient and ethylene-insensitive double mutant plants display essentially additive phenotypes, and we found no evidence that SLs influence ethylene synthesis or vice versa.


Assuntos
Lactonas/farmacologia , Ervilhas/fisiologia , Rhizobium/fisiologia , Transdução de Sinais , Fatores de Transcrição/metabolismo , Regulação para Baixo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Lactonas/metabolismo , Lipopolissacarídeos/farmacologia , Mutação , Ervilhas/efeitos dos fármacos , Ervilhas/genética , Ervilhas/microbiologia , Fenótipo , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nodulação/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/microbiologia , Raízes de Plantas/fisiologia , Simbiose/efeitos dos fármacos , Fatores de Transcrição/genética
20.
Appl Environ Microbiol ; 83(17)2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28667114

RESUMO

Antibiotics are important for treating bacterial infection; however, efficacies and side effects of antibiotics vary in medicine and experimental models. A few studies have correlated microbiota composition variations with health outcomes in response to antibiotics; however, no study has demonstrated causality. We had noted variation in colonic expression of C-type lectins, regenerating islet-derived protein 3ß (Reg3ß) and Reg3γ, after metronidazole treatment in a mouse model. To investigate the effects of specific variations in the preexisting microbiome on host response to antibiotics, mice harboring a normal microbiota were allocated to 4 treatments in a 2-by-2 factorial arrangement with or without commensal Escherichia coli and with or without metronidazole in drinking water. E. coli colonized readily without causing a notable shift in the microbiota or host response. Metronidazole administration reduced microbiota biodiversity, indicated by decreased Chao1 and Shannon index values, and altered microbiota composition. However, the presence of E. coli strongly affected metronidazole-induced microbiota shifts. Remarkably, this single commensal bacterium in the context of a complex population led to variations in host responses to metronidazole treatment, including increased expression of antimicrobial peptides Reg3ß and Reg3γ and intestinal inflammation indicated by tumor necrosis factor alpha levels. Similar results were obtained from 2-week antibiotic exposure and with additional E. coli isolates. The results of this proof-of-concept study indicate that even minor variations in initial commensal microbiota can drive shifts in microbial composition and host response after antibiotic administration. As well as providing an explanation for variability in animal models using antibiotics, the findings encourage the development of personalized medication in antibiotic therapies.IMPORTANCE This work provides an understanding of variability in studies where antibiotics are used to alter the gut microbiota to generate a host response. Furthermore, although providing evidence only for the one antibiotic, the study demonstrated that initial gut microbial composition is a key factor driving host response to antibiotic administration, creating a compelling argument for considering personalized medication based on individual variations in gut microbiota.


Assuntos
Antibacterianos/administração & dosagem , Bactérias/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Metronidazol/administração & dosagem , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Escherichia coli/fisiologia , Feminino , Humanos , Intestinos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Simbiose/efeitos dos fármacos
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