Removal of antibiotics by four microalgae-based systems for swine wastewater treatment under different phytohormone treatment.

This study examined the removal of typical antibiotics from simulated swine wastewater. Microalgae-bacteria/fungi symbioses were constructed using Chlorella ellipsoidea, endophytic bacteria (S395-2), and Clonostachys rosea as biomaterials. The growth, photosynthetic performance, and removal of three types of antibiotics (tetracyclines, sulfonamides, and quinolones) induced by four phytohormones were analyzed in each system. The results showed that all four phytohormones effectively improved the tolerance of symbiotic strains against antibiotic stress; strigolactones (GR24) achieved the best performance. At 10-9 M, GR24 achieved the best removal of antibiotics by C. elliptica + S395-2 + C. rosea symbiosis. The average removals of tetracycline, sulfonamide, and quinolone by this system reached 96.2-99.4 %, 75.2-81.1 %, and 66.8-69.9 %, respectively. The results of this study help to develop appropriate bio enhancement strategies as well as design and operate algal-bacterial-fungal symbiotic processes for the treatment of antibiotics-containing wastewater.

Immune checkpoint inhibitors unleash pathogenic immune responses against the microbiota.

Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects are of unclear etiology and impact virtually all organ systems, with the most common being sites colonized by the microbiota such as the skin and gastrointestinal tract. Here, we establish a mouse model of commensal bacteria-driven skin irAEs and demonstrate that immune checkpoint inhibition unleashes commensal-specific inflammatory T cell responses. These aberrant responses were dependent on production of IL-17 by commensal-specific T cells and induced pathology that recapitulated the cutaneous inflammation seen in patients treated with ICIs. Importantly, aberrant T cell responses unleashed by ICIs were sufficient to perpetuate inflammatory memory responses to the microbiota months following the cessation of treatment. Altogether, we have established a mouse model of skin irAEs and reveal that ICIs unleash aberrant immune responses against skin commensals, with long-lasting inflammatory consequences.

Brassinosteroids Benefit Plants Performance by Augmenting Arbuscular Mycorrhizal Symbiosis.

Arbuscular mycorrhizal (AM) play an important role in improving plant growth and development. The interaction between phytohormones and AM symbiosis is gradually revealed. Here we examined the effect of Brassinosteroids (BR) on AM symbiosis and discussed the synergistic promotion of plant growth by BR and AM symbiosis. The xylophyta Eucalyptus grandis Hill (E. grandis) was inoculated with AM fungi Rhizoglomus irregularis R197198 (R. irregularis) and treated with different concentrations (0, 1, 10, and 100 nM) of 24-epibrassinolide (24-epiBL) for 6 weeks. With the increase of 24-epiBL concentration, E. grandis growth was firstly promoted and then inhibited, but inoculation with AM fungi alleviated this inhibition. 24-epiBL and R. irregularis colonization significantly improved E. grandis growth and antioxidant system response, and the synergistic effect was the best. Compared with the control group, 24-epiBL treatment significantly increased the mycorrhizal colonization and arbuscular abundance of AM fungi R. irregular in E. grandis roots. The expression of AM symbiosis maker genes was significantly increased by 24-epiBL treatment. Both 24-epiBL treatment and AM colonization upregulated gibberellins (GA) synthesis genes, but no inhibition caused by GA levels was found. 24-epiBL is a kind of synthetic highly active BR. Based on the results of 24-epiBL treatment, we hypothesized that BR actively regulates AM symbiosis regulates AM symbiosis without affecting GA-INSENSITIVE DWARF1 (GID1)-DELLA expression. The synergistic treatment of BR and AM symbiosis can significantly promote the growth and development of plants. IMPORTANCE Brassinosteroids (BR) and Arbuscular mycorrhizas (AM) symbiosis play an important role in improving plant growth and development. Previous studies have shown that there is a complex regulatory network between phytohormones and AM symbiosis. However, the interactions of BR-signaling and AM symbiosis are still poorly understood. Our results suggest that BR actively regulates the colonization and development of AM fungi, and AM fungal colonization can alleviate the inhibition of plant growth caused by excessive BR. In addition, BR actively regulates AM symbiosis, but does not primarily mediate gibberellins-DELLA interaction. The synergistic treatment of BR and AM symbiosis can significantly promote the growth and development of plants. The conclusions of this study provide a reference for phytohormones-AM symbiosis interaction.

Protective Effect of Lactiplantibacillus plantarum 1201 Combined with Galactooligosaccharide on Carbon Tetrachloride-Induced Acute Liver Injury in Mice.

Acute liver injury (ALI) has a high mortality rate of approximately 20-40%, and it is imperative to find complementary and alternative drugs for treating ALI. A carbon tetrachloride (CCl4)-induced ALI mouse model was established to explore whether dietary intervention can alleviate ALI in mice. Intestinal flora, intestinal integrity, biomarkers of hepatic function, systemic inflammation, autophagy, and apoptosis signals were detected through a real-time PCR, hematoxylin-eosin staining, 16S rRNA gene sequencing, and so on. The results showed that Lactiplantibacillus plantarum 1201 had a strongly antioxidant ability, and galactooligosaccharide (GOS) could boost its growth. Based on these findings, the combination of L. plantarum 1201 and GOS, the synbiotic, was applied to prevent CCl4-induced ALI in mice. The current research proved that GOS promoted the intestinal colonization of L. plantarum 1201, and the synbiotic improved the antioxidant capacity of the host, regulated the intestinal flora, repaired the intestinal barrier, inhibited the activation of the MAPK/NF-κB pathway, and then inhibited the apoptosis and autophagy pathways, relieving inflammation and liver oxidation; thereby, the ALI of mice was alleviated. These results suggest that synbiotics may become a new research direction for liver-protecting drugs.

Insecticide resistance by a host-symbiont reciprocal detoxification.

Insecticide resistance is one of the most serious problems in contemporary agriculture and public health. Although recent studies revealed that insect gut symbionts contribute to resistance, the symbiont-mediated detoxification process remains unclear. Here we report the in vivo detoxification process of an organophosphorus insecticide, fenitrothion, in the bean bug Riptortus pedestris. Using transcriptomics and reverse genetics, we reveal that gut symbiotic bacteria degrade this insecticide through a horizontally acquired insecticide-degrading enzyme into the non-insecticidal but bactericidal compound 3-methyl-4-nitrophenol, which is subsequently excreted by the host insect. This integrated "host-symbiont reciprocal detoxification relay" enables the simultaneous maintenance of symbiosis and efficient insecticide degradation. We also find that the symbiont-mediated detoxification process is analogous to the insect genome-encoded fenitrothion detoxification system present in other insects. Our findings highlight the capacity of symbiosis, combined with horizontal gene transfer in the environment, as a powerful strategy for an insect to instantly eliminate a toxic chemical compound, which could play a critical role in the human-pest arms race.

Unravelling the collateral damage of antibiotics on gut bacteria.

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species2. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for ß-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal3-5 and human6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.

Commensal-Related Changes in the Epidermal Barrier Function Lead to Alterations in the Benzo[a]Pyrene Metabolite Profile and Its Distribution in 3D Skin.

Polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (B[a]P) are among the most abundant environmental pollutants, resulting in continuous exposure of human skin and its microbiota. However, effects of the latter on B[a]P toxicity, absorption, metabolism, and distribution in humans remain unclear. Here, we demonstrate that the skin microbiota does metabolize B[a]P on and in human skin in situ, using a recently developed commensal skin model. In this model, microbial metabolism leads to high concentrations of known microbial B[a]P metabolites on the surface as well as in the epidermal layers. In contrast to what was observed for uncolonized skin, B[a]P and its metabolites were subject to altered rates of skin penetration and diffusion, resulting in up to 58% reduction of metabolites recovered from basal culture medium. The results indicate the reason for this altered behavior to be a microbially induced strengthening of the epidermal barrier. Concomitantly, colonized models showed decreased formation and penetration of the ultimate carcinogen B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), leading, in consequence, to fewer BPDE-DNA adducts being formed. Befittingly, transcript and expression levels of key proteins for repairing environmentally induced DNA damage such as xeroderma pigmentosum complementation group C (XPC) were also found to be reduced in the commensal models, as was expression of B[a]P-associated cytochrome P450-dependent monooxygenases (CYPs). The results show that the microbiome can have significant effects on the toxicology of external chemical impacts. The respective effects rely on a complex interplay between microbial and host metabolism and microbe-host interactions, all of which cannot be adequately assessed using single-system studies. IMPORTANCE Exposure to xenobiotics has repeatedly been associated with adverse health effects. While the majority of reported cases relate to direct substance effects, there is increasing evidence that microbiome-dependent metabolism of xenobiotic substances likewise has direct adverse effects on the host. This can be due to microbial biotransformation of compounds, interaction between the microbiota and the host's endogenous detoxification enzymes, or altered xenobiotic bioavailability. However, there are hardly any studies addressing the complex interplay of such interactions in situ and less so in human test systems. Using a recently developed microbially competent three-dimensional (3D) skin model, we show here for the first time how commensal influence on skin physiology and gene transcription paradoxically modulates PAH toxicity.

Probiotic and commensal gut microbial therapies in multiple sclerosis and its animal models: a comprehensive review.

The need for alternative treatments for multiple sclerosis (MS) has triggered copious amounts of research into microbial therapies focused on manipulating the microbiota-gut-brain axis. This comprehensive review was intended to present and systematically evaluate the current clinical and preclinical evidence for various probiotic and commensal gut microbial therapies as treatments for MS, using the Bradford Hill criteria (BHC) as a multi-parameter assessment rubric. Literature searches were performed to identify a total of 37 relevant studies (6 human, 31 animal), including 28 probiotic therapy and 9 commensal therapy studies. In addition to presenting qualitative summaries of these findings, therapeutic evidence for each bacterial formulation was assessed using the BHC to generate summative scores. These scores, which encompassed study quality, replication, and other considerations, were used to rank the most promising therapies and highlight deficiencies. Several therapeutic formulations, including VSL#3, Lactobacillus paracasei, Bifidobacterium animalis, E. coli Nissle 1917, and Prevotella histicola, emerged as the most promising. In contrast, a number of other therapies were hindered by limited evidence of replicable findings and other criteria, which need to be addressed by future studies in order to harness gut microbial therapies to ultimately provide cheaper, safer, and more durable treatments for MS.

Inhibition of a nutritional endosymbiont by glyphosate abolishes mutualistic benefit on cuticle synthesis in Oryzaephilus surinamensis.

Glyphosate is widely used as a herbicide, but recent studies begin to reveal its detrimental side effects on animals by targeting the shikimate pathway of associated gut microorganisms. However, its impact on nutritional endosymbionts in insects remains poorly understood. Here, we sequenced the tiny, shikimate pathway encoding symbiont genome of the sawtoothed grain beetle Oryzaephilus surinamensis. Decreased titers of the aromatic amino acid tyrosine in symbiont-depleted beetles underscore the symbionts' ability to synthesize prephenate as the precursor for host tyrosine synthesis and its importance for cuticle sclerotization and melanization. Glyphosate exposure inhibited symbiont establishment during host development and abolished the mutualistic benefit on cuticle synthesis in adults, which could be partially rescued by dietary tyrosine supplementation. Furthermore, phylogenetic analyses indicate that the shikimate pathways of many nutritional endosymbionts likewise contain a glyphosate sensitive 5-enolpyruvylshikimate-3-phosphate synthase. These findings highlight the importance of symbiont-mediated tyrosine supplementation for cuticle biosynthesis in insects, but also paint an alarming scenario regarding the use of glyphosate in light of recent declines in insect populations.

The influence of ethylene, gibberellins and brassinosteroids on energy and nitrogen-fixation metabolites in nodule tissue.

Legume nodules are a unique plant organ that contain nitrogen-fixing rhizobial bacteria. For this interaction to be mutually beneficial, plant and bacterial metabolism must be precisely co-ordinated. Plant hormones are known to play essential roles during the establishment of legume-rhizobial symbioses but their role in subsequent nodule metabolism has not been explored in any depth. The plant hormones brassinosteroids, ethylene and gibberellins influence legume infection, nodule number and in some cases nodule function. In this paper, the influence of these hormones on nodule metabolism was examined in a series of well characterised pea mutants with altered hormone biosynthesis or response. A targeted set of metabolites involved in nutrient exchange and nitrogen fixation was examined in nodule tissue of mutant and wild type plants. Gibberellin-deficiency had a major negative impact on the level of several major dicarboxylates supplied to rhizobia by the plant and also led to a significant deficit in the amino acids involved in glutamine-aspartate transamination, consistent with the limited bacteroid development and low fixation rate of gibberellin-deficient na mutant nodules. In contrast, no major effects of brassinosteroid-deficiency or ethylene-insensitivity on the key metabolites in these pathways were found. Therefore, although all three hormones influence infection and nodule number, only gibberellin is important for the establishment of a functional nodule metabolome.

The Eagle effect in the Wolbachia-worm symbiosis.

BACKGROUND: Onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis) are two human neglected tropical diseases that cause major disabilities. Mass administration of drugs targeting the microfilarial stage has reduced transmission and eliminated these diseases in several countries but a macrofilaricidal drug that kills or sterilizes the adult worms is critically needed to eradicate the diseases. The causative agents of onchocerciasis and lymphatic filariasis are filarial worms that harbor the endosymbiotic bacterium Wolbachia. Because filarial worms depend on Wolbachia for reproduction and survival, drugs targeting Wolbachia hold great promise as a means to eliminate these diseases. METHODS: To better understand the relationship between Wolbachia and its worm host, adult Brugia pahangi were exposed to varying concentrations of doxycycline, minocycline, tetracycline and rifampicin in vitro and assessed for Wolbachia numbers and worm motility. Worm motility was monitored using the Worminator system, and Wolbachia titers were assessed by qPCR of the single copy gene wsp from Wolbachia and gst from Brugia to calculate IC50s and in time course experiments. Confocal microscopy was also used to quantify Wolbachia located at the distal tip region of worm ovaries to assess the effects of antibiotic treatment in this region of the worm where Wolbachia are transmitted vertically to the microfilarial stage. RESULTS: Worms treated with higher concentrations of antibiotics had higher Wolbachia titers, i.e. as antibiotic concentrations increased there was a corresponding increase in Wolbachia titers. As the concentration of antibiotic increased, worms stopped moving and never recovered despite maintaining Wolbachia titers comparable to controls. Thus, worms were rendered moribund by the higher concentrations of antibiotics but Wolbachia persisted suggesting that these antibiotics may act directly on the worms at high concentration. Surprisingly, in contrast to these results, antibiotics given at low concentrations reduced Wolbachia titers. CONCLUSION: Wolbachia in B. pahangi display a counterintuitive dose response known as the "Eagle effect." This effect in Wolbachia suggests a common underlying mechanism that allows diverse bacterial and fungal species to persist despite exposure to high concentrations of antimicrobial compounds. To our knowledge this is the first report of this phenomenon occurring in an intracellular endosymbiont, Wolbachia, in its filarial host.

Antibacterial FANA oligonucleotides as a novel approach for managing the Huanglongbing pathosystem.

Candidatus Liberibacter asiaticus (CLas), a bacterium transmitted by the Asian citrus psyllid, Diaphorina citri, is the causal agent of citrus greening disease, or Huanglongbng (HLB). Currently, vector population suppression with insecticides and tree removal are the most effective strategies for managing the HLB pathosystem. In this study, we assessed the bactericidal capabilities of 2'-deoxy-2'-fluoro-D-arabinonucleic acid antisense oligonucleotides (FANA ASO) both in vitro and in vivo by (1) confirming their capacity to penetrate insect cells, (2) silencing bacterial essential genes, and (3) quantifying reductions in bacterial titer and D. citri transmission. We confirmed that FANA ASO are able to penetrate insect cells without the use of a delivery agent. Expression of an essential gene in the D. citri endosymbiont, Wolbachia (wDi), significantly decreased by 30% following incubation with a wDi-specific FANA ASO. Viability of isolated wDi cells also decreased in response to the FANA ASO treatment. Delivery of a CLas-specific FANA ASO to infected adult D. citri in feeding assays resulted in significant silencing of a CLas essential gene. CLas relative density and transmission were significantly lower among D. citri fed FANA ASO in diet compared to untreated insects. Root infusions of a CLas-specific FANA ASO into infected Citrus trees significantly reduced CLas titer during a 30-day trial. Our results suggest that FANA ASO targeting insect-transmitted plant bacteria or insect endosymbionts may be useful tool for integrated management of agricultural pathogens.

Effect of zinc pyrithione shampoo treatment on skin commensal Malassezia.

Malassezia restricta and Malassezia globosa are lipid dependent commensal yeasts associated with dandruff. Antifungal actives such as zinc pyrithione are commonly used in antidandruff shampoos, although their efficacy is not clearly demonstrated. In this study, we assessed the efficacy of antifungal treatments on scalp Malassezia via a combination of culturomic and genomic detection methods. Zinc pyrithione inhibited Malassezia growth at low minimum inhibitory concentrations (MICs). In a longitudinal pilot study, quantitative polymerase chain reaction (qPCR) analysis showed a decrease in M. restricta on the scalp after zinc pyrithione treatment. These findings validate the antifungal efficacy of zinc pyrithione as a dandruff treatment. LAY ABSTRACT: Malassezia yeasts are associated with dandruff and seborrheic dermatitis. Zinc pyrithione is effective against Malassezia growth in vitro and when tested on human skin as a shampoo. These findings will be useful for investigating the role of Malassezia in skin microbiome intervention studies.

Endogenous gibberellins affect root nodule symbiosis via transcriptional regulation of NODULE INCEPTION in Lotus japonicus.

Legumes and nitrogen-fixing rhizobial bacteria establish root nodule symbiosis, which is orchestrated by several plant hormones. Exogenous addition of biologically active gibberellic acid (GA) is known to inhibit root nodule symbiosis. However, the precise role of GA has not been elucidated because of the trace amounts of these hormones in plants and the multiple functions of GAs. Here, we found that GA signaling acts as a key regulator in a long-distance negative-feedback system of root nodule symbiosis called autoregulation of nodulation (AON). GA biosynthesis is activated during nodule formation in and around the nodule vascular bundles, and bioactive GAs accumulate in the nodule. In addition, GA signaling induces expression of the symbiotic transcription factor NODULE INCEPTION (NIN) via a cis-acting region on the NIN promoter. Mutants with deletions of this cis-acting region have increased susceptibility to rhizobial infection and reduced GA-induced CLE-RS1 and CLE-RS2 expression, suggesting that the inhibitory effect of GAs occurs through AON. This is supported by the GA-insensitive phenotypes of an AON-defective mutant of HYPERNODULATION ABERRANT ROOT FORMATION1 (HAR1) and a reciprocal grafting experiment. Thus, endogenous GAs induce NIN expression via its GA-responsive cis-acting region, and subsequently the GA-induced NIN activates the AON system to regulate nodule formation.

Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections.

Current efforts to eliminate the neglected tropical diseases onchocerciasis and lymphatic filariasis, caused by the filarial nematodes Onchocerca volvulus and Wuchereria bancrofti or Brugia spp., respectively, are hampered by lack of a short-course macrofilaricidal-adult-worm killing-treatment. Anti-wolbachial antibiotics, e.g. doxycycline, target the essential Wolbachia endosymbionts of filariae and are a safe prototype adult-worm-sterilizing and macrofilaricidal regimen, in contrast to standard treatments with ivermectin or diethylcarbamazine, which mainly target the microfilariae. However, treatment regimens of 4-5 weeks necessary for doxycycline and contraindications limit its use. Therefore, we tested the preclinical anti-Wolbachia drug candidate Corallopyronin A (CorA) for in vivo efficacy during initial and chronic filarial infections in the Litomosoides sigmodontis rodent model. CorA treatment for 14 days beginning immediately after infection cleared >90% of Wolbachia endosymbionts from filariae and prevented development into adult worms. CorA treatment of patently infected microfilaremic gerbils for 14 days with 30 mg/kg twice a day (BID) achieved a sustained reduction of >99% of Wolbachia endosymbionts from adult filariae and microfilariae, followed by complete inhibition of filarial embryogenesis resulting in clearance of microfilariae. Combined treatment of CorA and albendazole, a drug currently co-administered during mass drug administrations and previously shown to enhance efficacy of anti-Wolbachia drugs, achieved microfilarial clearance after 7 days of treatment at a lower BID dose of 10 mg/kg CorA, a Human Equivalent Dose of 1.4 mg/kg. Importantly, this combination led to a significant reduction in the adult worm burden, which has not yet been published with other anti-Wolbachia candidates tested in this model. In summary, CorA is a preclinical candidate for filariasis, which significantly reduces treatment times required to achieve sustained Wolbachia depletion, clearance of microfilariae, and inhibition of embryogenesis. In combination with albendazole, CorA is robustly macrofilaricidal after 7 days of treatment and fulfills the Target Product Profile for a macrofilaricidal drug.

Effects of sponge-derived Ageladine A on the photosynthesis of different microalgal species and strains.

Fluorescent natural compounds have been identified in several marine hosts of microalgae. Their prevalence, and the energy the host is expending on their synthesis, suggests an important, yet poorly understood ecological role. It has been suggested that some of these natural products may enhance the photosynthesis of microbial symbionts. In this study, the effect of Ageladine A (Ag A), a pH-dependent fluorophore found in sponges of the genus Agelas, on the photosynthesis of nine microalgal species and strains was examined. The data showed that the variety of effects of Ag A additions differed between species, and even strains within a species. While in one strain of Synechococcus sp., the presence of Ag A increased gross photosynthesis under UV light exposure, it decreased in another. And while in the chlorophyte T. chuii overall metabolic activity was greatly reduced under all forms of lighting, photosynthesis in T. lutea was positively affected by the addition of Ag A. The variety of effects of Ag A on photosynthesis observed in this study indicate a complex interaction of Ag A with microalgal cells and suggests that a host may be able to shape its own symbiotic microbiome with self-produced natural products.

Antifungal activity of Xenorhabdus spp. and Photorhabdus spp. against the soybean pathogenic Sclerotinia sclerotiorum.

The fungus, Sclerotinia sclerotiorum, causes white mold disease and infects a broad spectrum of host plants (> 500), including soybean with yield losses of up to 70%. Biological control is a potential alternative for management of this severe plant pathogen, and relative to chemical fungicides, provides broad benefits to the environment, farmers and consumers. The symbiotic bacteria of entomopathogenic nematodes, Xenorhabdus spp. and Photorhabdus spp., are characterized by the production of antimicrobial compounds, which could serve as potential sources for new bio-fungicides. The objectives of this study were to assess cell-free supernatants (CFS) of 16 strains of these bacteria cultures on S. sclerotiorum mycelium growth; assess the volatiles of X. szentirmaii cultures on the fungus mycelium and sclerotium inhibition; and evaluate the X. szentirmaii cultures as well as their CFS on the protection of soybean seeds against the white mold disease. Among the 16 strains, the CFS of X. szentirmaii showed the highest fungicidal effect on growth of S. sclerotiorum. The CFS of X. szentirmaii inhibited > 98% of fungus growth from mycelium and sclerotia, whereas the volatiles generated by the bacterium culture inhibited to 100% of fungus growth and 100% of sclerotia production. The bacterial culture diluted to 33% in water and coated on soybean seeds inhibited S. sclerotiorum and protected soybean plants, allowing 78.3% of seed germination and 56.6% of plant development. Our findings indicate potential for a safe and novel control method for S. sclerotiorum in soybean. Moreover, this is the first study to indicate that volatile organic compounds from Xenorhabdus spp. can be used in plant disease suppression.

Health-Promoting Compounds in Stevia: The Effect of Mycorrhizal Symbiosis, Phosphorus Supply and Harvest Time.

This work aimed to establish the synergic role of arbuscular mycorrhizal fungi (AMF) symbiosis, phosphorus (P) fertilization and harvest time on the contents of stevia secondary metabolites. Consequently, steviol glycosides (SVglys) concentration and profile, total phenols and flavonoids as well as antioxidant assays, have been assessed in inoculated and no-inoculated plants, grown with or without P supply and collected at different growth stages(69, 89 and 123 days after transplanting).The obtained results suggest that the synthesis of stevia secondary metabolites is induced and/or modulated by all the investigated variability factors. In particular, AMF symbiosis promoted total SVglys content and positively influenced the concentration of some minor compounds (steviolbioside, dulcoside A and rebaudioside B), indicating a clear effect of mycorrhizal inoculation on SVglys biosynthetic pathway. Interestingly, only the mycorrhizal plants were able to synthesize rebaudioside B. In addition, P supply provided the highest levels of total phenols and flavonoids at leaf level, together with the maximum in vitro antioxidant activities (FRAP and ORAC). Finally, the harvest time carried out during the full vegetative phase enhanced the entire composition of the phytocomplex (steviolbioside, dulcoside A, stevioside, rebaudioside A, B, C. total phenols and flavonoids). Moreover, polyphenols and SVglys appeared to be the main contributors to the in vitro antioxidant capacity, while only total phenols mostly contributed to the cellular antioxidant activity (CAA). These findings provide original information about the role played by AMF in association with P supply, in modulating the accumulation of bioactive compounds during stevia growth. At the cultivation level, the control of these preharvest factors, together with the most appropriate harvest time, can be used as tools for improving the nutraceutical value of raw material, with particular attention to its exploitation as functional ingredient for food and dietary supplements and cosmetics.

The Skin Microbiome: A New Actor in Inflammatory Acne.

Our understanding of the role of Cutibacterium acnes in the pathophysiology of acne has recently undergone a paradigm shift: rather than C. acnes hyperproliferation, it is the loss of balance between the different C. acnes phylotypes, together with a dysbiosis of the skin microbiome, which results in acne development. The loss of diversity of C. acnes phylotypes acts as a trigger for innate immune system activation, leading to cutaneous inflammation. A predominance of C. acnes phylotype IA1 has been observed, with a more virulent profile in acne than in normal skin. Other bacteria, mainly Staphylococcus epidermis, are also implicated in acne. S. epidermidis and C. acnes interact and are critical for the regulation of skin homeostasis. Recent studies also showed that the gut microbiome is involved in acne, through interactions with the skin microbiome. As commonly used topical and systemic antibiotics induce cutaneous dysbiosis, our new understanding of acne pathophysiology has prompted a change in direction for acne treatment. In the future, the development of individualized acne therapies will allow targeting of the pathogenic strains, leaving the commensal strains intact. Such alternative treatments, involving modifications of the microbiome, will form the next generation of 'ecobiological' anti-inflammatory treatments.

Antibiotics create a shift from mutualism to competition in human gut communities with a longer-lasting impact on fungi than bacteria.

BACKGROUND: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing. RESULTS: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate. CONCLUSIONS: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.