scholarly journals The critical role of MetR/MetB/MetC/MetX in cysteine and methionine metabolism, fungal development and virulence of Alternaria alternata

2020 ◽  
Author(s):  
Yunpeng Gai ◽  
Lei Li ◽  
Haijie Ma ◽  
Brendan K. Riely ◽  
Bing Liu ◽  
...  
Keyword(s):  
Alternaria Alternata ◽  
Vegetative Growth ◽  
Critical Role ◽  
Phytopathogenic Fungi ◽  
Glutathione Metabolism ◽  
Methionine Metabolism ◽  
Fungal Development ◽  
Cellular Processes ◽  
Oxidative Tolerance ◽  
Ros Tolerance

Methionine is a unique sulfur-containing amino acid, which plays an important role in biological protein synthesis and various cellular processes. Here, we characterized the biological functions of AaMetB, AaMetC, and AaMetX in the tangerine pathotype of Alternaria alternata. Morphological analysis showed that the mutants lacking AaMetB, AaMetC, or AaMetX resulted in less aerial hypha and fewer conidia in artificial media. Pathogenicity analysis showed that AaMetB, AaMetC, and AaMetX are required for full virulence. The defects in vegetative growth, conidiation and virulence of ΔMetB, ΔMetC, and ΔMetX can be restored by exogenous methionine and homocysteine, indicating that AaMetB, AaMetC, and AaMetX are required for methionine biosynthesis. However, exogenous cysteine only restored the growth and virulence defects of ΔMetR but not ΔMetB/C/X, suggesting that AaMetR is essential for cysteine biosynthesis. Oxidant sensitivity assay showed that only ΔMetR is sensitive to H2O2 and many ROS-generating compounds, indicating that AaMetR is essential for oxidative tolerance. Interestingly, fungicides indoor bioassays showed that only the ΔMetR mutants are susceptive to chlorothalonil, a fungicide that could bind to the cysteine of glyceraldehyde-3-phosphate dehydrogenase. Comparative transcriptome analysis showed that the inactivation of MetB, MetC, MetX, or MetR significantly affected the expression of methionine metabolism-related genes. Moreover, the inactivation of AaMetR significantly affected the expression of many genes related to glutathione metabolism, which is essential for ROS tolerance. Taken together, our study provides genetic evidence to define the critical roles of AaMetB, AaMetC, AaMetX, and AaMetR in cysteine and methionine metabolism, fungal development and virulence of Alternaria alternata. IMPORTANCE The transcription factor METR regulating methionine metabolism is essential for reactive oxygen species (ROS) tolerance and virulence in many phytopathogenic fungi. However, the underlying regulatory mechanism of METR involved in this process is still unclear. In the present study, we generated AaMetB, AaMetC and AaMetX deletion mutants and compared these mutants with AaMetR disrupted mutants. Interestingly, we found that AaMetB, AaMetC and AaMetX are required for vegetative growth, conidiation, and pathogenicity in Alternaria alternata, but not for ROS tolerance and cysteine metabolism. Furthermore, we found that METR is involved in the biosynthesis of cysteine, which is an essential substrate for the biosynthesis of methionine and glutathione. This study emphasizes the critical roles of MetR, MetB, MetC, MetX in the regulation of cysteine and methionine metabolism, as well as the cross-link with glutathione-mediated ROS tolerance in phytopathogenic fungi, which provides a foundation for future investigations.

scholarly journals The Dynamin-Like GTPase FgSey1 Plays a Critical Role in Fungal Development and Virulence in Fusarium graminearum

2020 ◽  
Vol 86 (11) ◽  
Author(s):  
Xuefa Chong ◽  
Chenyu Wang ◽  
Yao Wang ◽  
Yixiao Wang ◽  
Liyuan Zhang ◽  
...  
Keyword(s):  
Fusarium Graminearum ◽  
Vegetative Growth ◽  
Animal Feed ◽  
Pathogenic Fungus ◽  
Critical Role ◽  
Effective Control ◽  
Economic Losses ◽  
Head Blight ◽  
Fungal Development ◽  
Content Type

ABSTRACT Fusarium graminearum, the main pathogenic fungus causing Fusarium head blight (FHB), produces deoxynivalenol (DON), a key virulence factor, which is synthesized in the endoplasmic reticulum (ER). Sey1/atlastin, a dynamin-like GTPase protein, is known to be required for homotypic fusion of ER membranes, but the functions of this protein are unknown in pathogenic fungi. Here, we characterized Sey1/atlastin homologue FgSey1 in F. graminearum. Like Sey1/atlastin, FgSey1 is located in the ER. The FgSEY1 deletion mutant exhibited significantly reduced vegetative growth, asexual development, DON biosynthesis, and virulence. Moreover, the ΔFgsey1 mutant was impaired in the formation of normal lipid droplets (LDs) and toxisomes, both of which participate in DON biosynthesis. The GTPase, helix bundle (HB), transmembrane segment (TM), and cytosolic tail (CT) domains of FgSey1 are essential for its function, but only the TM domain is responsible for its localization. Furthermore, the mutants FgSey1K63A and FgSey1T87A lacked GTPase activity and failed to rescue the defects of the ΔFgsey1 mutant. Collectively, our data suggest that the dynamin-like GTPase protein FgSey1 affects the generation of LDs and toxisomes and is required for DON biosynthesis and pathogenesis in F. graminearum. IMPORTANCE Fusarium graminearum is a major plant pathogen that causes Fusarium head blight (FHB) of wheats worldwide. In addition to reducing the plant yield, F. graminearum infection of wheats also results in the production of deoxynivalenol (DON) mycotoxins, which are harmful to humans and animals and therefore cause great economic losses through pollution of food products and animal feed. At present, effective strategies for controlling FHB are not available. Therefore, understanding the regulation mechanisms of fungal development, pathogenesis, and DON biosynthesis is important for the development of effective control strategies of this disease. In this study, we demonstrated that a dynamin-like GTPase protein Sey1/atlastin homologue, FgSey1, is required for vegetative growth, DON production, and pathogenicity in F. graminearum. Our results provide novel information on critical roles of FgSey1 in fungal pathogenicity; therefore, FgSey1 could be a potential target for effective control of the disease caused by F. graminearum.

scholarly journals Arginine Decarboxylase Is Essential for Pneumococcal Stress Responses

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 286
Author(s):  
Mary Frances Nakamya ◽  
Moses B. Ayoola ◽  
Leslie A. Shack ◽  
Mirghani Mohamed ◽  
Edwin Swiatlo ◽  
...  
Keyword(s):  
Stress Responses ◽  
Critical Role ◽  
Acid Stress ◽  
Arginine Decarboxylase ◽  
Arginine Deiminase ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Opportunistic Human Pathogen ◽  
Thiol Peroxidase ◽  
The Impact

Polyamines such as putrescine, cadaverine, and spermidine are small cationic molecules that play significant roles in cellular processes, including bacterial stress responses and host–pathogen interactions. Streptococcus pneumoniae is an opportunistic human pathogen, which causes several diseases that account for significant morbidity and mortality worldwide. As it transits through different host niches, S. pneumoniae is exposed to and must adapt to different types of stress in the host microenvironment. We earlier reported that S. pneumoniae TIGR4, which harbors an isogenic deletion of an arginine decarboxylase (ΔspeA), an enzyme that catalyzes the synthesis of agmatine in the polyamine synthesis pathway, has a reduced capsule. Here, we report the impact of arginine decarboxylase deletion on pneumococcal stress responses. Our results show that ΔspeA is more susceptible to oxidative, nitrosative, and acid stress compared to the wild-type strain. Gene expression analysis by qRT-PCR indicates that thiol peroxidase, a scavenger of reactive oxygen species and aguA from the arginine deiminase system, could be important for peroxide stress responses in a polyamine-dependent manner. Our results also show that speA is essential for endogenous hydrogen peroxide and glutathione production in S. pneumoniae. Taken together, our findings demonstrate the critical role of arginine decarboxylase in pneumococcal stress responses that could impact adaptation and survival in the host.

scholarly journals Effects of Chemical Mixtures on the Ovary

Reproduction ◽  
2021 ◽  
Author(s):  
Vasiliki E. Mourikes ◽  
Jodi A Flaws
Keyword(s):  
Ovarian Development ◽  
Steroid Hormone ◽  
Critical Role ◽  
Corpora Lutea ◽  
Chemical Mixtures ◽  
Hormone Production ◽  
Sex Steroid Hormone ◽  
Cellular Processes ◽  
Female Reproductive Health

The ovaries play a critical role in female reproductive health because they are the site of oocyte maturation and sex steroid hormone production. The unique cellular processes that take place within the ovary make it a susceptible target for chemical mixtures. Herein, we review the available data regarding the effects of chemical mixtures on the ovary, focusing on development, folliculogenesis, and steroidogenesis. The chemical mixtures discussed include those to which women are exposed to environmentally, occupationally, and medically. Following a brief introduction to chemical mixture components, we describe the effects of chemical mixtures on ovarian development, folliculogenesis, and steroidogenesis. Further, we discuss the effects of chemical mixtures on corpora lutea and transgenerational outcomes. Identifying the effects of chemical mixtures on the ovaries is paramount to preventing and treating mixture-inducing toxicity of the ovary that has long-term consequences such as infertility and ovarian disease.

Antifungal Activities of Some Indole Derivatives

2010 ◽  
Vol 65 (7-8) ◽  
pp. 437-439 ◽  
Author(s):  
Hui Xu ◽  
Qin Wang ◽  
Wen-Bin Yang
Keyword(s):  
Fusarium Oxysporum ◽  
Fusarium Graminearum ◽  
Broad Spectrum ◽  
Alternaria Alternata ◽  
Phytopathogenic Fungi ◽  
Pyricularia Oryzae ◽  
Indole Derivatives ◽  
Alternaria Brassicae ◽  
Antifungal Activities

Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide.

scholarly journals Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy

2019 ◽  
Vol 20 (9) ◽  
pp. 2241 ◽  
Author(s):  
Debarati Banik ◽  
Sara Moufarrij ◽  
Alejandro Villagra
Keyword(s):  
Histone Deacetylase Inhibitors ◽  
Critical Role ◽  
Preclinical Studies ◽  
Clinical Use ◽  
Combination Therapies ◽  
Drug Candidates ◽  
Cellular Processes ◽  
Fda Approval

Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. Finally, we have included examples of ongoing trials for each of the above categories of HDACis as standalone agents or in combination with immunotherapeutic approaches.

scholarly journals Crystal structure of yeast Sis1 peptide-binding fragment and Hsp70 Ssa1 C-terminal complex

2006 ◽  
Vol 398 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Jingzhi Li ◽  
Yunkun Wu ◽  
Xinguo Qian ◽  
Bingdong Sha
Keyword(s):  
Crystal Structure ◽  
Close Contact ◽  
Critical Role ◽  
Peptide Binding ◽  
Structural Basis ◽  
Cellular Processes ◽  
Terminal Form ◽  
Charged Residues ◽  
Domain I

Heat shock protein (Hsp) 40 facilitates the critical role of Hsp70 in a number of cellular processes such as protein folding, assembly, degradation and translocation in vivo. Hsp40 and Hsp70 stay in close contact to achieve these diverse functions. The conserved C-terminal EEVD motif in Hsp70 has been shown to regulate Hsp40–Hsp70 interaction by an unknown mechanism. Here, we provide a structural basis for this regulation by determining the crystal structure of yeast Hsp40 Sis1 peptide-binding fragment complexed with the Hsp70 Ssa1 C-terminal. The Ssa1 extreme C-terminal eight residues, G634PTVEEVD641, form a β-strand with the domain I of Sis1 peptide-binding fragment. Surprisingly, the Ssa1 C-terminal binds Sis1 at the site where Sis1 interacts with the non-native polypeptides. The negatively charged residues within the EEVD motif in Ssa1 C-terminal form extensive charge–charge interactions with the positively charged residues in Sis1. The structure-based mutagenesis data support the structural observations.

scholarly journals Tagging the proteasome active site β5 causes tag specific phenotypes in yeast

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenrick A. Waite ◽  
Alicia Burris ◽  
Jeroen Roelofs
Keyword(s):  
Nitrogen Starvation ◽  
Critical Role ◽  
26S Proteasome ◽  
Core Particle ◽  
Poor Growth ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
Storage Granules ◽  
Fluorescent Tags ◽  
Gfp Tag

Abstract The efficient and timely degradation of proteins is crucial for many cellular processes and to maintain general proteostasis. The proteasome, a complex multisubunit protease, plays a critical role in protein degradation. Therefore, it is important to understand the assembly, regulation, and localization of proteasome complexes in the cell under different conditions. Fluorescent tags are often utilized to study proteasomes. A GFP-tag on the β5 subunit, one of the core particle (CP) subunits with catalytic activity, has been shown to be incorporated into proteasomes and commonly used by the field. We report here that a tag on this subunit results in aberrant phenotypes that are not observed when several other CP subunits are tagged. These phenotypes appear in combination with other proteasome mutations and include poor growth, and, more significantly, altered 26S proteasome localization. In strains defective for autophagy, β5-GFP tagged proteasomes, unlike other CP tags, localize to granules upon nitrogen starvation. These granules are reflective of previously described proteasome storage granules but display unique properties. This suggests proteasomes with a β5-GFP tag are specifically recognized and sequestered depending on physiological conditions. In all, our data indicate the intricacy of tagging proteasomes, and possibly, large complexes in general.

scholarly journals Visualizing Nudivirus Assembly and Egress

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Sailakshmi Velamoor ◽  
Allan Mitchell ◽  
Bruno M. Humbel ◽  
WonMo Kim ◽  
Charlotte Pushparajan ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Structural Changes ◽  
Critical Role ◽  
Three Dimensional ◽  
Nuclear Compartment ◽  
Virion Assembly ◽  
Cellular Processes ◽  
Rhinoceros Beetle ◽  
Palm Trees ◽  
Unique Mechanism

ABSTRACT Enveloped viruses hijack cellular membranes in order to provide the necessary material for virion assembly. In particular, viruses that replicate and assemble inside the nucleus have developed special approaches to modify the nuclear landscape for their advantage. We used electron microscopy to investigate cellular changes occurring during nudivirus infection and we characterized a unique mechanism for assembly, packaging, and transport of new virions across the nuclear membrane and through the cytoplasm. Our three-dimensional reconstructions describe the complex remodeling of the nuclear membrane necessary to release vesicle-associated viruses into the cytoplasm. This is the first report of nuclear morphological reconfigurations that occur during nudiviral infection. IMPORTANCE The dynamics of nuclear envelope has a critical role in multiple cellular processes. However, little is known regarding the structural changes occurring inside the nucleus or at the inner and outer nuclear membranes. For viruses assembling inside the nucleus, remodeling of the intranuclear membrane plays an important role in the process of virion assembly. Here, we monitored the changes associated with viral infection in the case of nudiviruses. Our data revealed dramatic membrane remodeling inside the nuclear compartment during infection with Oryctes rhinoceros nudivirus, an important biocontrol agent against coconut rhinoceros beetle, a devastating pest for coconut and oil palm trees. Based on these findings, we propose a model for nudivirus assembly in which nuclear packaging occurs in fully enveloped virions.

Temporal Dynamics of Candidatus Liberibacter asiaticus Titer in Mature Leaves from Citrus sinensis cv Valencia Are Associated with Vegetative Growth

2019 ◽  
Vol 113 (2) ◽  
pp. 589-595 ◽  
Author(s):  
Freddy Ibanez ◽  
Lukasz L Stelinski
Keyword(s):  
Vegetative Growth ◽  
Citrus Sinensis ◽  
Temporal Dynamics ◽  
Critical Role ◽  
Insect Vector ◽  
In Planta ◽  
Mature Leaves ◽  
Candidatus Liberibacter ◽  
Liberibacter Asiaticus ◽  
The Impact

Abstract Huanglongbing, a highly destructive disease of citrus species, is associated with a fastidious, gram-negative, phloem-limited bacteria (Candidatus Liberibacter spp.). In Florida, the causative agent of Huanglongbing (HLB) is C. Liberibacter asiaticus (CLas) and it is transmitted by the insect vector, Asian citrus psyllid (Diaphorina citri Kuwayama). Previous investigations have revealed systemic infection of CLas with an erratic and uneven distribution of pathogen in tree phloem. However, previous investigations did not consider the potential impact of plant vegetative growth on presence/absence of CLas in planta. Our objectives were to determine: 1) the effect of vegetative growth of Citrus sinensis (L.) Osbeck cv Valencia on detection of CLas in mature leaves, and 2) the impact of CLas inoculation frequency on progression of CLas titer in citrus leaves through the first year of infection. Temporal dynamics of CLas detection were associated with vegetative flush growth. Surprisingly, there was no difference in CLas titer detected between plants exposed to infected vectors for a one-time 7 d inoculation access period, as compared with plants exposed to continuously breeding CLas-infected insects over the course of an entire year of plant infection. Our results suggest that the CLas bacterium is transported through phloem during annual movement of carbon compounds needed for vegetative plant growth, including transportation from roots to mature leaves. These results highlight the importance of vegetative growth on temporal dynamics of CLas in citrus, and suggest a critical role of the sink-source interaction on presence/absence of CLas in leaves.

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