scholarly journals Sphingolipid biosynthetic pathway is crucial for growth, biofilm formation and membrane integrity of Scedosporium boydii

2019 ◽  
Vol 11 (22) ◽  
pp. 2905-2917 ◽  
Author(s):  
Rodrigo Rollin-Pinheiro ◽  
Victor Pereira Rochetti ◽  
Mariana Ingrid Dutra da Silva Xisto ◽  
Livia Cristina Liporagi-Lopes ◽  
Beatriz Bastos ◽  
...  
Keyword(s):  
Cell Biology ◽  
Pathogenic Fungus ◽  
Membrane Integrity ◽  
Fungal Growth ◽  
Antifungal Drugs ◽  
Wide Range ◽  
Antifungal Potential ◽  
Sphingolipid Biosynthesis ◽  
Increased Susceptibility

Aim: Glycosphingolipids are conserved lipids displaying a variety of functions in fungal cells, such as determination of cell polarity and virulence. They have been considered as potent targets for new antifungal drugs. The present work aimed to test two inhibitors, myriocin and DL-threo-1-Phenyl-2-palmitoylamino-3-morpholino-1-propanol, in Scedosporium boydii, a pathogenic fungus which causes a wide range of disease. Materials & methods: Mass spectrometry, microscopy and cell biology approaches showed that treatment with both inhibitors led to defects in fungal growth and membrane integrity, and caused an increased susceptibility to the current antifungal agents. Conclusion: These data demonstrate the antifungal potential of drugs inhibiting sphingolipid biosynthesis, as well as the usefulness of sphingolipids as promising targets for the development of new therapeutic options.

scholarly journals Hex1, the Major Component of Woronin Bodies, Is Required for Normal Development, Pathogenicity, and Stress Response in the Plant Pathogenic Fungus Verticillium dahliae

2020 ◽  
Vol 6 (4) ◽  
pp. 344
Author(s):  
Vasileios Vangalis ◽  
Ioannis A. Papaioannou ◽  
Emmanouil A. Markakis ◽  
Michael Knop ◽  
Milton A. Typas
Keyword(s):  
Stress Response ◽  
Verticillium Dahliae ◽  
Pathogenic Fungus ◽  
Membrane Integrity ◽  
Fungal Growth ◽  
Growth Physiology ◽  
Cellular Processes ◽  
Ros Homeostasis ◽  
Membrane Bound ◽  
Septal Pores

Woronin bodies are membrane-bound organelles of filamentous ascomycetes that mediate hyphal compartmentalization by plugging septal pores upon hyphal damage. Their major component is the peroxisomal protein Hex1, which has also been implicated in additional cellular processes in fungi. Here, we analyzed the Hex1 homolog of Verticillium dahliae, an important asexual plant pathogen, and we report its pleiotropic involvement in fungal growth, physiology, stress response, and pathogenicity. Alternative splicing of the Vdhex1 gene can lead to the production of two Hex1 isoforms, which are structurally similar to their Neurospora crassa homolog. We show that VdHex1 is targeted to the septum, consistently with its demonstrated function in sealing hyphal compartments to prevent excessive cytoplasmic bleeding upon injury. Furthermore, our investigation provides direct evidence for significant contributions of Hex1 in growth and morphogenesis, as well as in asexual reproduction capacity. We discovered that Hex1 is required both for normal responses to osmotic stress and factors that affect the cell wall and plasma-membrane integrity, and for normal resistance to oxidative stress and reactive oxygen species (ROS) homeostasis. The Vdhex1 mutant exhibited diminished ability to colonize and cause disease on eggplant. Overall, we show that Hex1 has fundamentally important multifaceted roles in the biology of V. dahliae.

scholarly journals Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Rodrigo Rollin-Pinheiro ◽  
Yuri de Castro Almeida ◽  
Victor Pereira Rochetti ◽  
Mariana Ingrid Dutra da Silva Xisto ◽  
Luana Pereira Borba-Santos ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Membrane Integrity ◽  
Antifungal Drugs ◽  
Mitochondrial Activity ◽  
Clinical Settings ◽  
Fungal Cell ◽  
Wide Range ◽  
Exogenous Addition ◽  
Species Production

Scedosporium and Lomentospora species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the in vitro antifungal activity of miltefosine against Scedosporium and Lomentospora species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different Scedosporium and Lomentospora species at 2–4 µg/ml and reduced biofilm formation. The loss of membrane integrity in Scedosporium aurantiacum caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and Scedosporium and Lomentospora cells, highlighting its potential use as new antifungal drug in the future.

scholarly journals Hex1, the Major Component of Woronin Bodies, is Required for Normal Development, Pathogenicity and Stress Response in the Plant Pathogenic Fungus Verticillium dahliae

2020 ◽  
Author(s):  
Vasileios Vangalis ◽  
Ioannis A. Papaioannou ◽  
Emmanouil A. Markakis ◽  
Michael Knop ◽  
Milton A. Typas
Keyword(s):  
Stress Response ◽  
Verticillium Dahliae ◽  
Pathogenic Fungus ◽  
Membrane Integrity ◽  
Fungal Growth ◽  
Growth Physiology ◽  
Cellular Processes ◽  
Ros Homeostasis ◽  
Membrane Bound ◽  
Septal Pores

AbstractWoronin bodies are membrane-bound organelles of filamentous ascomycetes that mediate hyphal compartmentalization by plugging septal pores upon hyphal damage. Their major component is the peroxisomal protein Hex1, which has also been implicated in additional cellular processes in fungi. Here, we analyzed the Hex1 homolog of Verticillium dahliae, an important asexual plant pathogen, and we report its pleiotropic involvement in fungal growth, physiology, stress response and pathogenicity. Alternative splicing of the Vdhex1 gene can lead to the production of two Hex1 isoforms, which are structurally similar to their Neurospora crassa homolog. We show that VdHex1 is targeted to the septum, consistently with its demonstrated function in sealing hyphal compartments to prevent excessive cytoplasmic bleeding upon injury. Furthermore, our investigation provides direct evidence for significant contributions of Hex1 in growth and morphogenesis, as well as in asexual reproduction capacity. We discovered that Hex1 is required both for normal responses to osmotic stress and factors that affect the cell wall and plasma membrane integrity, and for normal resistance to oxidative stress and ROS homeostasis. The Vdhex1 mutant exhibited diminished ability to colonize and cause disease on eggplant. Overall, we show that Hex1 has fundamentally important multifaceted roles in the biology of V. dahliae.

scholarly journals Imaging invasive fungal growth and inflammation in NADPH oxidase-deficient zebrafish

2019 ◽  
Author(s):  
Taylor J. Schoen ◽  
Emily E. Rosowski ◽  
Benjamin P. Knox ◽  
David Bennin ◽  
Nancy P. Keller ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Aspergillus Nidulans ◽  
Pathogenic Fungus ◽  
Fungal Growth ◽  
Neutrophil Infiltration ◽  
Host Pathogen Interaction ◽  
Phagocyte Nadph Oxidase ◽  
Invasive Infections ◽  
Increased Susceptibility

AbstractNeutrophils are primary cells of the innate immune system that generate reactive oxygen species (ROS) and mediate host defense. Deficient phagocyte NADPH oxidase (PHOX) function leads to chronic granulomatous disease (CGD) that is characterized by invasive infections including those by the generally non-pathogenic fungusAspergillus nidulans. The role of neutrophil ROS in this specific host-pathogen interaction remains unclear. Here, we exploit the optical transparency of zebrafish to image the effects of neutrophil ROS on invasive fungal growth and neutrophil behavior in response toAspergillus nidulans. In a wild-type host,A. nidulansgerminates rapidly and elicits a robust inflammatory response with efficient fungal clearance. PHOX-deficient larvae have increased susceptibility to invasiveA. nidulansinfection despite robust neutrophil infiltration. Expression of p22phoxspecifically in neutrophils does not affect fungal germination but instead limits the area of fungal growth and excessive neutrophil inflammation and is sufficient to restore host survival in p22phox-deficient larvae. These findings suggest that neutrophil ROS limits invasive fungal growth and has immunomodulatory activities that contribute to the specific susceptibility of PHOX-deficient hosts to invasiveA. nidulansinfection.

scholarly journals Exploration of Novel TOSMIC Tethered Imidazo[1,2-a]pyridine Compounds for the Development of Potential Antifungal Drug Candidate.

2021 ◽  
Author(s):  
Pratibha Shukla ◽  
Deepa Deswal ◽  
Mansi Pandit ◽  
N Latha ◽  
Divyank Mahajan ◽  
...  
Keyword(s):  
Fungal Growth ◽  
Drug Candidate ◽  
Fluorescent Properties ◽  
Fungal Cell ◽  
Antifungal Effect ◽  
Antifungal Potential ◽  
Confocal Images ◽  
Fungal Growth Inhibition

Abstract New candidates of imidazo [1, 2-a] pyridine were designed by combining 2-amino pyridine, TOSMIC isocyanide and various assorted aldehydes were synthesized to explore their antioxidant and antifungal potential. The design of these derivatives was based on utilizing the antifungal potential of azoles and TOSMIC moiety. These derivatives were synthesized by adopting multi-component reaction methodology, as it serves as a rapid and efficient tool to target structurally diverse heterocyclic compounds in quantitative yield. The resulting imidazo [1, 2-a] pyridine derivatives were structurally verified by 1HNMR and 13CNMR. The compounds were analyzed for their antioxidant and fluorescent properties and it was observed that compound 15 depicted good fluorescence and antioxidant potential. Additionally, the compounds were evaluated for their antifungal potential against both Aspergillus fumigatus 3007 & Candida albicans 3018 and it was observed that all the compounds had moderate to significant antifungal effect. Confocal images depicted the porous nature of compound treated fungal cell membranes leading to fungal growth inhibition. Molecular docking was performed to establish the interaction with the target enzyme (Lanosterol 14 alpha demethylase) which also corroborated with the in vitro results. In silico tools were employed to determine drug-likeliness of the compounds along with determination of ADME properties.

DINAMIKA POLITIK PERSETUJUAN BERSAMA TENTANG PENETAPAN DESA ADAT DI KABUPATEN ROKAN HULU TAHUN 2014

2017 ◽  
Vol 15 (1) ◽  
pp. 21
Author(s):  
Haryo Suganda ◽  
Raja Muhammad Amin
Keyword(s):  
Regulatory Region ◽  
Field Research ◽  
Analysis Techniques ◽  
Political Dynamics ◽  
Political Interests ◽  
Wide Range ◽  
Information Method ◽  
Qualitative Descriptive ◽  
The Village

This study is motivated the identification of policies issued by the regional Governmentof Rokan Hulu in the form of Regulatory region number 1 by 2015 on the determination of thevillage and Indigenous Village. Political dynamics based on various interests against themanufacture of, and decision-making in the process of formation of the corresponding localregulations determination of Indigenous Villages in the Rokan Hulu is impacted to a verysignificantamount of changes from the initial draft of the number i.e. 21 (twenty one) the villagebecame Customary 89 (eighty-nine) the Indigenous Villages who have passed. Type of thisresearch is a qualitative descriptive data analysis techniques. The research aims to describe theState of the real situation in a systematic and accurate fact analysis unit or related research, aswell as observations of the field based on the data (information). Method of data collectionwas done with interviews, documentation, and observations through fieldwork (field research).The results of the research on the process of discussion of the draft local regulations andmutual agreement about Designation of Indigenous Villages in the Rokan Hulu is, showed thatthe political dynamics that occur due to the presence of various political interests, rejectionorally by Villagers who were judged to have met the requirements of Draft Regulations to beformulated and the area for the set to be Indigenous Villages, and also there is a desire fromsome villages in the yet to Draft local regulations in order to set the Indigenous village , there isa wide range of interests of these aspects influenced the agreement to assign the entire localVillage which is in the Rokan Hulu become Indigenous village, and the village of Transmigrationinto administrative Villages where the initiator of the changes in the number of IndigenousVillages in the Rokan Hulu it is the desire of the local Government of its own.

Control of Winged Waterprimrose (Jussiaea decurrens) and Northern Jointvetch (Aeschynomene virginica) with Fungal Pathogens

Weed Science ◽  
1979 ◽  
Vol 27 (5) ◽  
pp. 497-501 ◽  
Author(s):  
C. D. Boyette ◽  
G. E. Templeton ◽  
R. J. Smith
Keyword(s):  
Oryza Sativa ◽  
Glycine Max ◽  
Fungal Pathogens ◽  
Liquid Culture ◽  
Field Experiments ◽  
Colletotrichum Gloeosporioides ◽  
Pathogenic Fungus ◽  
Field Tests ◽  
Wide Range ◽  
Growing Region

An indigenous, host-specific, pathogenic fungus that parasitizes winged waterprimrose [Jussiaea decurrens(Walt.) DC.] is endemic in the rice growing region of Arkansas. The fungus was isolated and identified asColletotrichum gloeosporioides(Penz.) Sacc. f.sp. jussiaeae(CGJ). It is highly specific for parasitism of winged waterprimrose and not parasitic on creeping waterprimrose (J. repensL. var.glabrescensKtze.), rice (Oryza sativaL.), soybeans [Glycine max(L.) Merr.], cotton (Gossypium hirsutumL.), or 4 other crops and 13 other weeds. The fungus was physiologically distinct from C.gloeosporioides(Penz.) Sacc. f. sp.aeschynomene(CGA), an endemic anthracnose pathogen of northern jointvetch[Aeschynomene virginica(L.) B.S.P.], as indicated by cross inoculations of both weeds. Culture in the laboratory and inoculation of winged waterprimrose in greenhouse, growth chamber and field experiments indicated that the pathogen was stable, specific, and virulent in a wide range of environments. The pathogen yielded large quantities of spores in liquid culture. It is suitable for control of winged waterprimrose. Winged waterprimrose and northern jointvetch were controlled in greenhouse and field tests by application of spore mixtures of CGJ and CGA at concentrations of 1 to 2 million spores/ml of each fungus in 94 L/ha of water; the fungi did not damage rice or nontarget crops.

scholarly journals Recent Developments in the Determination of Biomarkers of Tobacco Smoke Exposure in Biological Specimens: A Review

2021 ◽  
Vol 18 (4) ◽  
pp. 1768
Author(s):  
Hernâni Marques ◽  
Pedro Cruz-Vicente ◽  
Tiago Rosado ◽  
Mário Barroso ◽  
Luís A. Passarinha ◽  
...  
Keyword(s):  
Tobacco Smoke ◽  
Solid Phase ◽  
Smoke Exposure ◽  
Tobacco Smoke Exposure ◽  
World Health ◽  
Second Hand Smoke ◽  
Tobacco Exposure ◽  
Wide Range ◽  
Recent Developments

Environmental tobacco smoke exposure (ETS) and smoking have been described as the most prevalent factors in the development of certain diseases worldwide. According to the World Health Organization, more than 8 million people die every year due to exposure to tobacco, around 7 million due to direct ETS and the remaining due to exposure to second-hand smoke. Both active and second-hand exposure can be measured and controlled using specific biomarkers of tobacco and its derivatives, allowing the development of more efficient public health policies. Exposure to these compounds can be measured using different methods (involving for instance liquid- or gas-chromatographic procedures) in a wide range of biological specimens to estimate the type and degree of tobacco exposure. In recent years, a lot of research has been carried out using different extraction methods and different analytical equipment; this way, liquid–liquid extraction, solid-phase extraction or even miniaturized procedures have been used, followed by chromatographic analysis coupled mainly to mass spectrometric detection. Through this type of methodologies, second-hand smokers can be distinguished from active smokers, and this is also valid for e-cigarettes and vapers, among others, using their specific biomarkers. This review will focus on recent developments in the determination of tobacco smoke biomarkers, including nicotine and other tobacco alkaloids, specific nitrosamines, polycyclic aromatic hydrocarbons, etc. The methods for their detection will be discussed in detail, as well as the potential use of threshold values to distinguish between types of exposure.

scholarly journals The Interaction between the Sheet/Tool Surface Texture and the Friction/Galling Behaviour on Aluminium Deep Drawing Operations

Metals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 979
Author(s):  
Alaitz Zabala ◽  
Lander Galdos ◽  
Chris Childs ◽  
Iñigo Llavori ◽  
Andrea Aginagalde ◽  
...  
Keyword(s):  
Lightweight Design ◽  
Severity Index ◽  
Tribological Behaviour ◽  
Die Surface ◽  
Tool Surface ◽  
Strip Drawing ◽  
Aluminium Sheets ◽  
Increased Susceptibility

The increasing demands for lightweight design in the transport industry have led to an extensive use of lightweight materials such as aluminium alloys. The forming of aluminium sheets however presents significant challenges due to the low formability and the increased susceptibility to galling. The use of tailored workpieces and controlled die roughness surfaces are common strategies to improve the tribological behaviour, whilst galling is still not well understood. This work is aimed at analysing the interplay between the sheet and tool surface roughness on the friction and galling performance. Different degrees of Electro Discharge Texturing (EDT) textures were generated in AA1050 material strips, and tooling presenting different polishing degrees were prepared. Strip drawing tests were carried out to model the tribological condition and results were corroborated through cup drawing tests. A new galling severity index (GSI) is presented for a quick and quantitative determination of both galling occurrence and severity. The present study underlines the key role of die topography and the potential of die surface functionalization for galling prevention.

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