scholarly journals Characterization of the chorismate mutase effector (SsCm1) from Sclerotinia sclerotiorum

2015 ◽  
Author(s):  
Martin B. Dickman ◽  
Oded Yarden
Keyword(s):  
Secondary Metabolites ◽  
Sclerotinia Sclerotiorum ◽  
Plant Cell Wall ◽  
Defense Mechanism ◽  
Critical Role ◽  
Host Tissue ◽  
Chorismate Mutase ◽  
Host Cells ◽  
Fungal Virulence ◽  
Wide Range

Sclerotinia sclerotiorum is a filamentous fungus (mold) that causes plant disease. It has an extremely wide range of hosts (>400 species) and causes considerable damage (annual multimillion dollar losses) in economically important crops. It has proven difficult to control (culturally or chemically) and host resistance to this fungus has generally been inadequate. It is believed that this fungus occurs in almost every country. Virulence of this aggressive pathogen is bolstered by a wide array of plant cell wall degrading enzymes and various compounds (secondary metabolites) produced by the fungus. It is well established that plant pathogenic fungi secrete proteins and small molecules that interact with host cells and play a critical role in disease development. Such secreted proteins have been collectively designated as “effectors”. Plant resistance against some pathogens can be mediated by recognition of such effectors. Alternatively, effectors can interfere with plant defense. Some such effectors are recognized by the host plant and can culminate in a programmed cell death (PCD) resistant response. During the course of this study, we analyzed an effector in Sclerotiniasclerotiorum. This specific effector, SsCM1 is the protein chorismatemutase, which is an enzyme involved in a pathway which is important in the production of important amino acids, such a Tryptophan. We have characterized the Sclerotiniaeffector, SsCM1, and have shown that inactivation of Sscm1 does not affect fungal vegetative growth, development or production of oxalic acid (one of this fungus’ secondary metabolites associated with disease) production. However, yhis does result in reduced fungal virulence. We show that, unexpectedly, the SsCM1 protein translocates to the host chloroplast, and demonstrated that this process is required for full fungal virulence. We have also determined that the fungal SsCM1 protein can interact with similar proteins produced by the host. In addition, we have shown that the fungal SsCM1 is able to suppress at least some of the effects imposed by reactive oxygen species which are produced as a defense mechanism by the host. Last, but not least, the results of our studies have provided evidence contradicting the current dogma on at least some of the mechanist aspects of how this pathogen infects the host. Contrary to previousons, indicating that this pathogen kills its host by use of metabolites and enzymes that degrade the host tissue (a process called necrotrophy), we now know that at least in the early phases of infection, the fungus interacts with live host tissue (a phenomenon known as biotrophy). Taken together, the results of our studies provide novel insights concerning the mechanistic aspects of Sclerotinia-host interactions. We hope this information will be used to interfere with the disease cycle in a manner that will protect plants from this devastating fungus.

scholarly journals PP2Ac Modulates AMPK-Mediated Induction of Autophagy in Mycobacterium bovis—Infected Macrophages

2019 ◽  
Vol 20 (23) ◽  
pp. 6030
Author(s):  
Hussain ◽  
Zhao ◽  
Shah ◽  
Sabir ◽  
Wang ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Defense Mechanism ◽  
Kinase Inhibitor ◽  
Inhibitory Effect ◽  
Immune Defense ◽  
Host Cells ◽  
Human Beings ◽  
Ampk Signaling ◽  
Autophagy Induction ◽  
Wide Range

Mycobacterium bovis (M. bovis) is the causative agent of bovine tuberculosis in cattle population across the world. Human beings are at equal risk of developing tuberculosis beside a wide range of M. bovis infections in animal species. Autophagic sequestration and degradation of intracellular pathogens is a major innate immune defense mechanism adopted by host cells for the control of intracellular infections. It has been reported previously that the catalytic subunit of protein phosphatase 2A (PP2Ac) is crucial for regulating AMP-activated protein kinase (AMPK)-mediated autophagic signaling pathways, yet its role in tuberculosis is still unclear. Here, we demonstrated that M. bovis infection increased PP2Ac expression in murine macrophages, while nilotinib a tyrosine kinase inhibitor (TKI) significantly suppressed PP2Ac expression. In addition, we observed that TKI-induced AMPK activation was dependent on PP2Ac regulation, indicating the contributory role of PP2Ac towards autophagy induction. Furthermore, we found that the activation of AMPK signaling is vital for the regulating autophagy during M. bovis infection. Finally, the transient inhibition of PP2Ac expression enhanced the inhibitory effect of TKI-nilotinib on intracellular survival and multiplication of M. bovis in macrophages by regulating the host’s immune responses. Based on these observations, we suggest that PP2Ac should be exploited as a promising molecular target to intervene in host–pathogen interactions for the development of new therapeutic strategies towards the control of M. bovis infections in humans and animals.

scholarly journals Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins

2021 ◽  
Vol 17 (2) ◽  
pp. e1009102
Author(s):  
Nan Song ◽  
Lihong Chen ◽  
Zhemin Zhou ◽  
Xingmei Ren ◽  
Bo Liu ◽  
...  
Keyword(s):  
Evolutionary Dynamics ◽  
Critical Role ◽  
Host Cells ◽  
Bacterial Genomes ◽  
Biological Pest Control ◽  
Core Domain ◽  
Hypervariable Regions ◽  
Specific Distribution ◽  
Genome Wide ◽  
Wide Range

Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is translocated into host cells by an injectosome nanomachine comprising the other subunits. Currently the pathogenic roles and distribution of Tc toxins among different bacterial genera remain unclear. Here we have performed a comprehensive genome-wide analysis, and established a database that includes 1,608 identified Tc loci containing 2,528 TcC proteins in 1,421 Gram-negative and positive bacterial genomes. Our findings indicate that TcCs conform to the architecture of typical polymorphic toxins, with C-terminal hypervariable regions (HVR) encoding more than 100 different classes of putative toxic domains, most of which have not been previously recognized. Based on further analysis of Tc loci in the genomes of all Salmonella and Yersinia strains in EnteroBase, a “two-level” evolutionary dynamics scenario is proposed for TcC homologues. This scenario implies that the conserved TcC RHS core domain plays a critical role in the taxonomical specific distribution of TcC HVRs. This study provides an extensive resource for the future development of Tc toxins as valuable agrochemical tools. It furthermore implies that Tc proteins, which are encoded by a wide range of pathogens, represent an important versatile toxin superfamily with diverse pathogenic mechanisms.

Associated microflora of medicinal ferns: biotechnological potentials and possible applications

2016 ◽  
Vol 5 (03) ◽  
pp. 4927 ◽  
Author(s):  
Shubhi Srivastava ◽  
Paul A. K.
Keyword(s):  
Secondary Metabolites ◽  
Growth Promotion ◽  
Biological Activities ◽  
Hydrolytic Enzymes ◽  
In Vitro Production ◽  
Wide Range ◽  
Negative Effect ◽  
Bacteria And Fungi

Plant associated microorganisms that colonize the upper and internal tissues of roots, stems, leaves and flowers of healthy plants without causing any visible harmful or negative effect on their host. Diversity of microbes have been extensively studied in a wide variety of vascular plants and shown to promote plant establishment, growth and development and impart resistance against pathogenic infections. Ferns and their associated microbes have also attracted the attention of the scientific communities as sources of novel bioactive secondary metabolites. The ferns and fern alleles, which are well adapted to diverse environmental conditions, produce various secondary metabolites such as flavonoids, steroids, alkaloids, phenols, triterpenoid compounds, variety of amino acids and fatty acids along with some unique metabolites as adaptive features and are traditionally used for human health and medicine. In this review attention has been focused to prepare a comprehensive account of ethnomedicinal properties of some common ferns and fern alleles. Association of bacteria and fungi in the rhizosphere, phyllosphere and endosphere of these medicinally important ferns and their interaction with the host plant has been emphasized keeping in view their possible biotechnological potentials and applications. The processes of host-microbe interaction leading to establishment and colonization of endophytes are less-well characterized in comparison to rhizospheric and phyllospheric microflora. However, the endophytes are possessing same characteristics as rhizospheric and phyllospheric to stimulate the in vivo synthesis as well as in vitro production of secondary metabolites with a wide range of biological activities such as plant growth promotion by production of phytohormones, siderophores, fixation of nitrogen, and phosphate solubilization. Synthesis of pharmaceutically important products such as anticancer compounds, antioxidants, antimicrobials, antiviral substances and hydrolytic enzymes could be some of the promising areas of research and commercial exploitation.

Bioprospecting Cryptogams as Potential Source of Unique Biodynamic Phytochemicals with Diverse Pharmaceutical Applications

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Brahma N. Singh ◽  
Garima Pandey ◽  
Prateeksha ◽  
J. Kumar
Keyword(s):  
Secondary Metabolites ◽  
Higher Plants ◽  
New Drugs ◽  
Terrestrial Plants ◽  
Pharmacological Activities ◽  
Therapeutic Drugs ◽  
Potential Source ◽  
Therapeutic Value ◽  
Wide Range ◽  
Novel Structures

With the advent of green pharmaceuticals, the secondary metabolites derived from plants have provided numerous leads for the development of a wide range of therapeutic drugs; however the discovery of new drugs with novel structures has declined in the past few years. Cryptogams including lichens, bryophytes, and pteridophytes represent a group of small terrestrial plants that remain relatively untouched in the drug discovery process though some have been used as ethnomedicines by various tribes worldwide. Studies of their secondary metabolites are recent but reveal unique secondary metabolites which are not synthesized by higher plants. These compounds can have the potential to develop more potential herbal drugs for prevention and treatment of diseases The present article . deals with the secondary metabolites and pharmacological activities of cryptogams with an objective to bring them forth as potential source of biodynamic compounds of therapeutic value.

Shooting a Tiger

2018 ◽  
Author(s):  
Vijaya Ramadas Mandala
Keyword(s):  
Critical Role ◽  
Late Nineteenth Century ◽  
Way Of Life ◽  
Colonial India ◽  
British Raj ◽  
Early Colonial ◽  
Wide Range ◽  
Forest Legislation ◽  
Imperial Governance ◽  
North And South

The main contention of Shooting a Tiger is that hunting during the colonial period was not merely a recreational activity, but a practice intimately connected with imperial governance. The book positions shikar or hunting at the heart of colonial rule by demonstrating that, for the British in India, it served as a political, practical, and symbolic apparatus in the consolidation of power and rule during the nineteenth and early twentieth centuries. The book analyses early colonial hunting during the Company period, and then surveys different aspects of hunting during the high imperial decades in the later nineteenth and early twentieth centuries. The book draws upon an impressive array of archival material and uses a wide range of evidence to support its contentions. It examines hunting at a variety of social and ethnic levels—military, administrative, elite, princely India, Indian professional hunters, and in terms of Indian auxiliaries and (sometimes) resisters. It also deals with different geographical contexts—the plains, the mountains, north and south India. The exclusive privilege of hunting exercised by the ruling classes, following colonial forest legislation, continued to be extended to the Indian princes who played a critical role in sustaining the lavish hunts that became the hallmark of the late nineteenth-century British Raj. Hunting was also a way of life in colonial India, undertaken by officials and soldiers alike alongside their everyday duties, necessary for their mental sustenance and vital for the smooth operation of the colonial administration. There are also two final chapters on conservation, particularly the last chapter focusing on two British hunter-turned-conservationists, Jim Corbett and Colonel Richard Burton.

scholarly journals Comparative Metabolite Profile, Biological Activity and Overall Quality of Three Lettuce (Lactuca sativa L., Asteraceae) Cultivars in Response to Sulfur Nutrition

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 713
Author(s):  
Muna Ali Abdalla ◽  
Fengjie Li ◽  
Arlette Wenzel-Storjohann ◽  
Saad Sulieman ◽  
Deniz Tasdemir ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Plant Growth ◽  
Sesquiterpene Lactones ◽  
Critical Role ◽  
Soluble Sugars ◽  
Radical Scavenging ◽  
Metabolite Profile ◽  
Water Soluble ◽  
Radical Scavenger ◽  
Higher Plant

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), Hawking RZ (green multi-leaf lettuce, V2), and Barlach RZ (red multi-leaf, V3) were subjected to two S-treatments in the form of magnesium sulfate (+S) or magnesium chloride (−S). Significant differences were observed under −S treatments, especially among V1 and V2 lettuce cultivars. These responses were reflected in the yield, levels of macro- and micro-nutrients, water-soluble sugars, and free inorganic anions. In comparison with the green cultivars (V1 and V2), the red-V3 cultivar revealed a greater acclimation to S starvation, as evidenced by relative higher plant growth. In contrast, the green cultivars showed higher capabilities in production and superior quality attributes under +S condition. As for secondary metabolites, sixteen compounds (e.g., sesquiterpene lactones, caffeoyl derivatives, caffeic acid hexose, 5-caffeoylquinic acid (5-OCQA), quercetin and luteolin glucoside derivatives) were annotated in all three cultivars with the aid of HPLC-DAD-MS-based untargeted metabolomics. Sesquiterpene lactone lactucin and anthocyanin cyanidin 3-O-galactoside were only detected in V1 and V3 cultivars, respectively. Based on the analyses, the V3 cultivar was the most potent radical scavenger, while V1 and V2 cultivars exhibited antibacterial activity against Staphylococcus aureus in response to S provision. Our study emphasizes the critical role of S nutrition in plant growth, acclimation, and nutritional quality. The judicious-S application can be adopted as a promising antimicrobial prototype for medical applications.

scholarly journals Identification of Putative Virulence Genes by DNA Methylation Studies in the Cereal Pathogen Fusarium graminearum

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1192
Author(s):  
Francesco Tini ◽  
Giovanni Beccari ◽  
Gianpiero Marconi ◽  
Andrea Porceddu ◽  
Micheal Sulyok ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Fusarium Graminearum ◽  
Environmental Changes ◽  
Virulent Strain ◽  
Fungal Virulence ◽  
Wheat Seedlings ◽  
Wide Range ◽  
Conidia Production ◽  
Natural Hosts

DNA methylation mediates organisms’ adaptations to environmental changes in a wide range of species. We investigated if a such a strategy is also adopted by Fusarium graminearum in regulating virulence toward its natural hosts. A virulent strain of this fungus was consecutively sub-cultured for 50 times (once a week) on potato dextrose agar. To assess the effect of subculturing on virulence, wheat seedlings and heads (cv. A416) were inoculated with subcultures (SC) 1, 23, and 50. SC50 was also used to re-infect (three times) wheat heads (SC50×3) to restore virulence. In vitro conidia production, colonies growth and secondary metabolites production were also determined for SC1, SC23, SC50, and SC50×3. Seedling stem base and head assays revealed a virulence decline of all subcultures, whereas virulence was restored in SC50×3. The same trend was observed in conidia production. The DNA isolated from SC50 and SC50×3 was subject to a methylation content-sensitive enzyme and double-digest, restriction-site-associated DNA technique (ddRAD-MCSeEd). DNA methylation analysis indicated 1024 genes, whose methylation levels changed in response to the inoculation on a healthy host after subculturing. Several of these genes are already known to be involved in virulence by functional analysis. These results demonstrate that the physiological shifts following sub-culturing have an impact on genomic DNA methylation levels and suggest that the ddRAD-MCSeEd approach can be an important tool for detecting genes potentially related to fungal virulence.

scholarly journals Protective Effect of Osmundacetone against Neurological Cell Death Caused by Oxidative Glutamate Toxicity

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 328
Author(s):  
Tuy An Trinh ◽  
Young Hye Seo ◽  
Sungyoul Choi ◽  
Jun Lee ◽  
Ki Sung Kang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Defense Mechanism ◽  
Neuroprotective Effect ◽  
Glutamate Release ◽  
Chromatin Condensation ◽  
Critical Role ◽  
Glutamate Toxicity ◽  
Heme Oxygenase 1 ◽  
Brain Functions

Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 μM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.

scholarly journals Proteomic Analysis of Zeb1 Interactome in Breast Carcinoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3143
Author(s):  
Sergey E. Parfenyev ◽  
Sergey V. Shabelnikov ◽  
Danila Y. Pozdnyakov ◽  
Olga O. Gnedina ◽  
Leonid S. Adonin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Critical Role ◽  
Malignant Neoplasm ◽  
Malignant Neoplasms ◽  
Breast Cancer Patients ◽  
Survival Prognosis ◽  
Mesenchymal Transition ◽  
Wide Range

Breast cancer is the most frequently diagnosed malignant neoplasm and the second leading cause of cancer death among women. Epithelial-to-mesenchymal Transition (EMT) plays a critical role in the organism development, providing cell migration and tissue formation. However, its erroneous activation in malignancies can serve as the basis for the dissemination of cancer cells and metastasis. The Zeb1 transcription factor, which regulates the EMT activation, has been shown to play an essential role in malignant transformation. This factor is involved in many signaling pathways that influence a wide range of cellular functions via interacting with many proteins that affect its transcriptional functions. Importantly, the interactome of Zeb1 depends on the cellular context. Here, using the inducible expression of Zeb1 in epithelial breast cancer cells, we identified a substantial list of novel potential Zeb1 interaction partners, including proteins involved in the formation of malignant neoplasms, such as ATP-dependent RNA helicase DDX17and a component of the NURD repressor complex, CTBP2. We confirmed the presence of the selected interactors by immunoblotting with specific antibodies. Further, we demonstrated that co-expression of Zeb1 and CTBP2 in breast cancer patients correlated with the poor survival prognosis, thus signifying the functionality of the Zeb1–CTBP2 interaction.

scholarly journals A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amelia E. Sancilio ◽  
Richard T. D’Aquila ◽  
Elizabeth M. McNally ◽  
Matthew P. Velez ◽  
Michael G. Ison ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Venous Blood ◽  
Host Cells ◽  
Dried Blood Spot ◽  
Blood Collection ◽  
Widespread Application ◽  
Live Virus ◽  
Dilution Series ◽  
Wide Range ◽  
Blood Spot

AbstractThe spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample. Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV). Dilution series produced the expected pattern of dose–response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % surrogate neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples. Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying inhibition of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.

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