Trichoderma secondary metabolites active on plants and fungal pathogens

Beneficial microbes typically produce bioactive molecules that can affect the interactions of plants with their pathogens. Many secondary metabolites may also have antibiotic properties, which enable the producing microbe to inhibit and/or kill other microorganisms i.e. competing for a nutritional niche. Indeed, some of these compounds have been found to play an important role in the biocontrol of plant diseases by various beneficial microbes used world-wide for crop protection and bio-fertilization. In addition to direct toxic activity against plant pathogens, biocontrol-related metabolites may also increase disease resistance by triggering systemic plant defence activity, and/or enhance root and shoot growth. Fungi belonging to the Trichoderma genus are well known producers of secondary metabolites with a direct activity against phytopathogens and compounds that substantially affect the metabolism of the plant. The widescale application of selected metabolites to induce host resistance and/or to promote crop yield may become a reality in the near future and represents a powerful tool for the implementation of IPM strategies

Plant Dynamic Metabolic Response to Bacteriophage Treatment After Xanthomonas campestris pv. campestris Infection

Periodic epidemics of black rot disease occur worldwide causing substantial yield losses. Xanthomonas campestris pv. campestris (Xcc) represents one of the most common bacteria able to cause the above disease in cruciferous plants such as broccoli, cabbage, cauliflower, and Arabidopsis thaliana. In agriculture, several strategies are being developed to contain the Xanthomonas infection. The use of bacteriophages could represent a valid and efficient approach to overcome this widespread phenomenon. Several studies have highlighted the potential usefulness of implementing phage therapy to control plant diseases as well as Xcc infection. In the present study, we characterized the effect of a lytic phage on the plant Brassica oleracea var. gongylodes infected with Xcc and, for the first time, the correlated plant metabolic response. The results highlighted the potential benefits of bacteriophages: reduction of bacterium proliferation, alteration of the biofilm structure and/or modulation of the plant metabolism and defense response

An Algebraic Approach for Decoding Spread Codes

In this paper we study spread codes: a family of constant-dimension codes for random linear network coding. In other words, the codewords are full-rank matrices of size (k x n) with entries in a finite field F_q. Spread codes are a family of optimal codes with maximal minimum distance. We give a minimum-distance decoding algorithm which requires O((n-k)k^3) operations over an extension field F_{q^k}. Our algorithm is more efficient than the previous ones in the literature, when the dimension k of the codewords is small with respect to n. The decoding algorithm takes advantage of the algebraic structure of the code, and it uses original results on minors of a matrix and on the factorization of polynomials over finite fields

A multi-model assessment of the impact of currents, waves and wind in modelling surface drifters and oil spill

Validation of oil spill forecasting systems suffers from a lack of data due to the scarcity of oil slick in situ and satellite observations. Drifters (surface drifting buoys) are often considered as proxy for oil spill to overcome this problem. However, they can have different designs and consequently behave in a different way at sea, making it not straightforward to use them for oil spill model validation purposes and to account for surface currents, waves and wind when modelling them. Stemming from the need to validate the MEDESS4MS (Mediterranean Decision Support System for Marine Safety) multi-model oil spill prediction system, which allows access to several ocean, wave and meteorological operational model forecasts, an exercise at sea was carried out to collect a consistent dataset of oil slick satellite observations, in situ data and trajectories of different type of drifters. The exercise, called MEDESS4MS Serious Game 1 (SG1), took place in the Elba Island region (Western Mediterranean Sea) during May 2014. Satellite images covering the MEDESS4MS SG1 exercise area were acquired every day and, in the case an oil spill was observed from satellite, vessels of the Italian Coast Guard (ITCG) were sent in situ to confirm the presence of the pollution. During the exercise one oil slick was found in situ and drifters, with different water-following characteristics, were effectively deployed into the oil slick and then monitored in the following days. Although it was not possible to compare the oil slick and drifter trajectories due to a lack of satellite observations of the same oil slick in the following days, the oil slick observations in situ and drifters trajectories were used to evaluate the quality of MEDESS4MS multi-model currents, waves and winds by using the MEDSLIK-II oil spill model. The response of the drifters to surface ocean currents, different Stokes drift parameterizations and wind drag has been examined. We found that the surface ocean currents mainly drive the transport of completely submerged drifters. The accuracy of the simulations increases with higher resolution currents and with addition of the Stokes drift, which is better estimated when provided by wave models. The wind drag improves the modelling of drifter trajectories only in the case of partially emerged drifters, otherwise it leads to an incorrect reproduction of the drifters׳ direction, which is particularly evident in high speed wind conditions

Modulation of Tomato Response to Rhizoctonia solani by Trichoderma harzianum and Its Secondary Metabolite Harzianic Acid

The present study investigated the transcriptomic and metabolomic changes elicited in tomato plants (Solanum lycopersicum cv. Micro-Tom) following treatments with the biocontrol agent Trichoderma harzianum strain M10 or its purified secondary metabolite harzianic acid (HA), in the presence or the absence of the soil-borne pathogen Rhizoctonia solani. Transcriptomic analysis allowed the identification of differentially expressed genes (DEGs) that play a pivotal role in resistance to biotic stress. Overall, the results support the ability of T. harzianum M10 to activate defense responses in infected tomato plants. An induction of hormone-mediated signaling was observed, as shown by the up-regulation of genes involved in the ethylene and jasmonate (ET/JA) and salicylic acid (SA)-mediated signaling pathways. Further, the protective action of T. harzianum on the host was revealed by the over-expression of genes able to detoxify cells from reactive oxygen species (ROS). On the other hand, HA treatment also stimulated tomato response to the pathogen by inducing the expression of several genes involved in defense response (including protease inhibitors, resistance proteins like CC-NBS-LRR) and hormone interplay. The accumulation of steroidal glycoalkaloids in the plant after treatments with either T. harzianum or HA, as determined by metabolomic analysis, confirmed the complexity of the plant response to beneficial microbes, demonstrating that these microorganisms are also capable of activating the chemical defenses

Phosphodiesterase 3B Is Localized in Caveolae and Smooth ER in Mouse Hepatocytes and Is Important in the Regulation of Glucose and Lipid Metabolism

Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes

Expression and Regulation of Cyclic Nucleotide Phosphodiesterases in Human and Rat Pancreatic Islets

As shown by transgenic mouse models and by using phosphodiesterase 3 (PDE3) inhibitors, PDE3B has an important role in the regulation of insulin secretion in pancreatic β-cells. However, very little is known about the regulation of the enzyme. Here, we show that PDE3B is activated in response to high glucose, insulin and cAMP elevation in rat pancreatic islets and INS-1 (832/13) cells. Activation by glucose was not affected by the presence of diazoxide. PDE3B activation was coupled to an increase as well as a decrease in total phosphorylation of the enzyme. In addition to PDE3B, several other PDEs were detected in human pancreatic islets: PDE1, PDE3, PDE4C, PDE7A, PDE8A and PDE10A. We conclude that PDE3B is activated in response to agents relevant for β-cell function and that activation is linked to increased as well as decreased phosphorylation of the enzyme. Moreover, we conclude that several PDEs are present in human pancreatic islets

Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

Inhaled prostanoids and phosphodiesterase (PDE) inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor), motapizone (PDE3 inhibitor) or 8-Methoxymethyl-IBMX (PDE1 inhibitor) synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within <20 min, without significant changes in blood gases or systemic hemodynamics. Infusion of 8-Methoxymethyl-IBMX, motapizone and sildenafil caused each a dose-dependent decrease in pulmonary artery pressure, with sildenafil possessing the highest efficacy and at the same time selectivity for the pulmonary circulation. When combining a per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone) with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of P(PA )reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor

Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

BACKGROUND: The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. METHODS: CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i) the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii) the anti-remodeling effect of long-term inhalation of tolafentrine (iii) the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. RESULTS: Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks), cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC) was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP) 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers), after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery muscularization. The upregulation of extracellular matrix regulation and adhesion genes was reduced by nearly 80% by inhalation of the tolafentrine. When assessed in vitro, tolafentrine blocked the enhanced PASMC migratory response. CONCLUSION: In conclusion, we demonstrate for the first time that inhalation of combined PDE3/4 inhibitor reverses pulmonary hypertension fully developed in response to monocrotaline in rats. This "reverse-remodeling" effect includes structural changes in the lung vascular wall and key molecular pathways of matrix regulation, concomitant with 60% normalization of hemodynamics