scholarly journals Sphingolipid Inhibitors as an Alternative to Treat Candidiasis Caused by Fluconazole-Resistant Strains

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 856
Author(s):  
Rodrigo Rollin-Pinheiro ◽  
Brayan Bayona-Pacheco ◽  
Levy Tenorio Sousa Domingos ◽  
Jose Alexandre da Rocha Curvelo ◽  
Gabriellen Menezes Migliani de Castro ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Wide Spectrum ◽  
Pathogenic Fungi ◽  
New Therapeutic Approaches ◽  
First Choice ◽  
Invasive Infections ◽  
Choice Of Treatment ◽  
Fluconazole Resistant ◽  
Susceptibility Tests ◽  
Aureobasidin A

Candida species are fungal pathogens known to cause a wide spectrum of diseases, and Candida albicans and Candida glabrata are the most common associated with invasive infections. A concerning aspect of invasive candidiasis is the emergence of resistant isolates, especially those highly resistant to fluconazole, the first choice of treatment for these infections. Fungal sphingolipids have been considered a potential target for new therapeutic approaches and some inhibitors have already been tested against pathogenic fungi. The present study therefore aimed to evaluate the action of two sphingolipid synthesis inhibitors, aureobasidin A and myriocin, against different C. albicans and C. glabrata strains, including clinical isolates resistant to fluconazole. Susceptibility tests of aureobasidin A and myriocin were performed using CLSI protocols, and their interaction with fluconazole was evaluated by a checkerboard protocol. All Candida strains tested were sensitive to both inhibitors. Regarding the evaluation of drug interaction, both aureobasidin A and myriocin were synergic with fluconazole, demonstrating that sphingolipid synthesis inhibition could enhance the effect of fluconazole. Thus, these results suggest that sphingolipid inhibitors in conjunction with fluconazole could be useful for treating candidiasis cases, especially those caused by fluconazole resistant isolates.

scholarly journals A Nanoemulsion as an Effective Treatment Against Human Pathogenic Fungi

2019 ◽  
Author(s):  
Alexis Garcia ◽  
Yong Yi Fan ◽  
Sandeep Vellanki ◽  
Eun Young Huh ◽  
DiFernando Vanegas ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Healing Process ◽  
Pathogenic Fungi ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Development Of Resistance

AbstractThe emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. An increase antifungal drug resistant fungi have posed a serious threat to patients. Combining these circumstances with a limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi. In this study we present the utilization of the nanoemulsion NB-201 to control human pathogenic fungi. We found that the NB-201 exhibited in vitro activity against C. albicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented enhanced healing process after subcutaneous infections by multidrug resistant C. albicans in a murine host system. NB-201 also exhibited in vitro growth inhibition activity against other fungal pathogens, including Cryptococcus spp, Aspergillus fumigatus, and Mucorales. Due to the nature of the activity of this nanoemulsion, there is a minimized chance of drug resistance to develop, thus presents a novel treatment to control fungal wound or skin infections.

Nonsurgical Therapies for Hepatocellular and Cholangiocellular Carcinoma

Swiss Surgery ◽  
1999 ◽  
Vol 5 (3) ◽  
pp. 116-121 ◽  
Author(s):  
Schmassmann
Keyword(s):  
Current Trend ◽  
Percutaneous Ethanol Injection ◽  
Cholangiocellular Carcinoma ◽  
Multidisciplinary Therapy ◽  
Term Survival ◽  
Ethanol Injection ◽  
First Choice ◽  
Tumor Stages ◽  
Choice Of Treatment ◽  
Advanced Stages

Surgical resection is the first choice of treatment for patients with hepatocellular (HCC) and cholangiocellular carcinomas. Prolongation of survival is, however, the only realistic goal for most patients, which can be often achieved by nonsurgical therapies. Inoperable patients with large or multiple HCCs are usually treated with transarterial chemoembolization (TACE) with lipiodol in combination with a chemotherapeutic drug and gelfoam. Three-year survival depends on the stage of the disease and is about 20%. Patients with earlier tumor stages (one or two tumor nodules less than 3cm in size) are suitable for treatment with percutaneous ethanol injection (PEI) alone or in combination with TACE. Several studies have shown that in these early stages, the 3-year survival rate is approximately 55%-70% in the actively treated patients which is significantly higher than in untreated patients. In advanced stages of the disease, TACE and PEI have no effect on survival and should not be performed. Some of these patients have been successfully treated with octreotide. Patients with inoperable cholangiocellular carcinoma are treated by endoscopic or percutaneous stent placement. If stenting does not achieve adequate biliary drainage, multidisciplinary therapy including internal / external radiotherapy or photodynamic therapy should be considered in patients with potential long-term survival. In conclusion, nonresectional therapies play an essential role in the therapy of inoperable hepato- and cholangiocellular carcinomas as they lead to satisfactory survival. Multidisciplinary therapy appears to be the current trend of management.

Surgery of ulcus cruris venosum

Phlebologie ◽  
2010 ◽  
Vol 39 (03) ◽  
pp. 156-162 ◽  
Author(s):  
C. Schwahn-Schreiber
Keyword(s):  
Subcutaneous Tissue ◽  
Ulcus Cruris ◽  
Healing Time ◽  
Ulcus Cruris Venosum ◽  
Venous Stasis ◽  
Morphological Alterations ◽  
First Choice ◽  
Choice Of Treatment ◽  
Chronic Compartment Syndrome ◽  
Shave Therapy

SummaryAdvanced chronic venous stasis syndrome is characterized by irreversible and self-perpetuating morphological alterations in the lower leg. A chronic inflammatory process results in sclerosis, which progresses from the skin to the subcutaneous tissue and ultimately the fascia, sometimes including muscle and ankle joint and leading to chronic compartment syndrome. To cure these severe alterations with non healing ulcers decompression of the compartments like paratibial fasciotomy with SEPS and crural fasciectomy or removal of sclerosis like shave therapy are successful surgical procedures. Indication should be adapted to the extension of ulcer. Indications of the operations and the techniques are described, complications and results are discussed. Due to ulcer extension especially shave therapy (removal of the sclerotic tissue epifascial) and crural fasciectomy (removal of sclerosis including fascia) are very successful with up to 80% healing rate, even in severe cases and even after long term (up to 8 years). Since shave therapy is easy, short and simple with short healing time, few complications and good aesthetical result it is the first choice of treatment for non healing leg ulcers. Fasci ectomy is reserved for special indications such as deep transfascial necrosis or failure of shave therapy.

SOYBEAN AND FLAX SELECTION METHODS

1970 ◽  
pp. 19-23
Author(s):  
V. М. Lukomets ◽  
S. V. Zelentsov
Keyword(s):  
High Resistance ◽  
Fungal Pathogens ◽  
Selection Process ◽  
Pathogenic Fungi ◽  
Cultivated Plants ◽  
Practical Implementation ◽  
Physiological Basis ◽  
Oil Crops ◽  
Soybean Genotypes ◽  
Genetically Determined

To improve the effectiveness of the soybeans and oil flax breeding, research to improve existing and develop new breeding methods are conducting in all-Russia Research institute of Oil Crops (Krasnodar). One of the improved methods for the soybean breeding, based on the use of sources of complexes of compensatory genes, is the CCG technology, which allows to create varieties with an increased yield of a heterotic level transmitted along the progeny for the entire life cycle of the variety. For the purpose of non-transgenic production of new traits, a theory of polyploid recombination of the genome (TPR) was formulated, which models the mechanism of the natural formation of polymorphism in the centers of origin of cultivated plants. On the basis of this theory, a method of breeding (TPR-technology) has been developed, which makes it possible to obtain recombinant reploids of soybeans and oil flax with an extended spectrum of traits. Of these reploids, the soybean lines with increased sucking force of the roots, providing high drought resistance, were distinguished; cold-resistant soybean lines, which stand in the phase of shoots of freezing to minus 5 °С; lines of oil flax with complete resistance to flax sickness of soil and high resistance to Fusarium; winter-hardy flax lines that withstand winter frosts down to minus 20–23 °С and ripen one and a half months earlier than spring sowings. Another original developed method is the ODCS-technology for isolating and selecting soybean genotypes with high resistance to fungal pathogens. The physiological basis of ODCS-technology is the blocking of osmotic nutrition of pathogenic fungi due to genetically determined increased osmotic pressure in the tissues of host plants. The practical implementation of CCG-, TPR- and ODKS-technologies in the selection process, allowed to create a whole series of soybean and oil flax varieties with improved or new traits.

scholarly journals Mitotic Recombination and Adaptive Genomic Changes in Human Pathogenic Fungi

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 901 ◽  
Author(s):  
Asiya Gusa ◽  
Sue Jinks-Robertson
Keyword(s):  
Fungal Pathogens ◽  
Repetitive Sequences ◽  
Pathogenic Fungi ◽  
Genetic Alterations ◽  
Fungal Species ◽  
Chronic Infections ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genomic Changes ◽  
Break Site ◽  
Repair Mechanisms

Genome rearrangements and ploidy alterations are important for adaptive change in the pathogenic fungal species Candida and Cryptococcus, which propagate primarily through clonal, asexual reproduction. These changes can occur during mitotic growth and lead to enhanced virulence, drug resistance, and persistence in chronic infections. Examples of microevolution during the course of infection were described in both human infections and mouse models. Recent discoveries defining the role of sexual, parasexual, and unisexual cycles in the evolution of these pathogenic fungi further expanded our understanding of the diversity found in and between species. During mitotic growth, damage to DNA in the form of double-strand breaks (DSBs) is repaired, and genome integrity is restored by the homologous recombination and non-homologous end-joining pathways. In addition to faithful repair, these pathways can introduce minor sequence alterations at the break site or lead to more extensive genetic alterations that include loss of heterozygosity, inversions, duplications, deletions, and translocations. In particular, the prevalence of repetitive sequences in fungal genomes provides opportunities for structural rearrangements to be generated by non-allelic (ectopic) recombination. In this review, we describe DSB repair mechanisms and the types of resulting genome alterations that were documented in the model yeast Saccharomyces cerevisiae. The relevance of similar recombination events to stress- and drug-related adaptations and in generating species diversity are discussed for the human fungal pathogens Candida albicans and Cryptococcus neoformans.

scholarly journals The Ustilago hordei–Barley Interaction is a Versatile System for Characterization of Fungal Effectors

2021 ◽  
Vol 7 (2) ◽  
pp. 86
Author(s):  
Bilal Ökmen ◽  
Daniela Schwammbach ◽  
Guus Bakkeren ◽  
Ulla Neumann ◽  
Gunther Doehlemann
Keyword(s):  
Fungal Pathogens ◽  
Plant Pathogens ◽  
Expression System ◽  
Pathogenic Fungi ◽  
Effector Proteins ◽  
Mating Partner ◽  
Fungal Virulence ◽  
Functional Studies ◽  
Infection Structures ◽  
Ustilago Hordei

Obligate biotrophic fungal pathogens, such as Blumeria graminis and Puccinia graminis, are amongst the most devastating plant pathogens, causing dramatic yield losses in many economically important crops worldwide. However, a lack of reliable tools for the efficient genetic transformation has hampered studies into the molecular basis of their virulence or pathogenicity. In this study, we present the Ustilago hordei–barley pathosystem as a model to characterize effectors from different plant pathogenic fungi. We generate U. hordei solopathogenic strains, which form infectious filaments without the presence of a compatible mating partner. Solopathogenic strains are suitable for heterologous expression system for fungal virulence factors. A highly efficient Crispr/Cas9 gene editing system is made available for U. hordei. In addition, U. hordei infection structures during barley colonization are analyzed using transmission electron microscopy, showing that U. hordei forms intracellular infection structures sharing high similarity to haustoria formed by obligate rust and powdery mildew fungi. Thus, U. hordei has high potential as a fungal expression platform for functional studies of heterologous effector proteins in barley.

Transgenic expression of gallerimycin, a novel antifungal insect defensin from the greater wax moth Galleria mellonella, confers resistance to pathogenic fungi in tobacco

2006 ◽  
Vol 387 (5) ◽  
pp. 549-557 ◽  
Author(s):  
Gregor Langen ◽  
Jafargholi Imani ◽  
Boran Altincicek ◽  
Gernot Kieseritzky ◽  
Karl-Heinz Kogel ◽  
...  
Keyword(s):  
Transgenic Tobacco ◽  
Fungal Pathogens ◽  
Galleria Mellonella ◽  
Ectopic Expression ◽  
Pathogenic Fungi ◽  
Transgenic Expression ◽  
Greater Wax Moth ◽  
Insect Defensin ◽  
Wax Moth

Abstract A cDNA encoding gallerimycin, a novel antifungal peptide from the greater wax moth Galleria mellonella, was isolated from a cDNA library of genes expressed during innate immune response in the caterpillars. Upon ectopic expression of gallerimycin in tobacco, using Agrobacterium tumefaciens as a vector, gallerimycin conferred resistance to the fungal pathogens Erysiphe cichoracearum and Sclerotinia minor. Quantification of gallerimycin mRNA in transgenic tobacco by real-time PCR confirmed transgenic expression under control of the inducible mannopine synthase promoter. Leaf sap and intercellular washing fluid from transgenic tobacco inhibited in vitro germination and growth of the fungal pathogens, demonstrating that gallerimycin is secreted into intercellular spaces. The feasibility of the use of gallerimycin to counteract fungal diseases in crop plants is discussed.

Sordarins: In Vitro Activities of New Antifungal Derivatives against Pathogenic Yeasts, Pneumocystis carinii, and Filamentous Fungi

1998 ◽  
Vol 42 (11) ◽  
pp. 2863-2869 ◽  
Author(s):  
E. Herreros ◽  
C. M. Martinez ◽  
M. J. Almela ◽  
M. S. Marriott ◽  
F. Gomez De Las Heras ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Filamentous Fungi ◽  
Fungal Pathogens ◽  
Pneumocystis Carinii ◽  
Pathogenic Fungi ◽  
Pseudallescheria Boydii ◽  
Absidia Corymbifera ◽  
Wide Range ◽  
Blastoschizomyces Capitatus

ABSTRACT GM 193663, GM 211676, GM 222712, and GM 237354 are new semisynthetic derivatives of the sordarin class. The in vitro antifungal activities of GM 193663, GM 211676, GM 222712, and GM 237354 against 111 clinical yeast isolates of Candida albicans,Candida kefyr, Candida glabrata, Candida parapsilosis, Candida krusei, and Cryptococcus neoformans were compared. The in vitro activities of some of these compounds against Pneumocystis carinii, 20 isolates each of Aspergillus fumigatus and Aspergillus flavus, and 30 isolates of emerging less-common mold pathogens and dermatophytes were also compared. The MICs of GM 193663, GM 211676, GM 222712, and GM 237354 at which 90% of the isolates were inhibited (MIC90s) were 0.03, 0.03, 0.004, and 0.015 μg/ml, respectively, for C. albicans, including strains with decreased susceptibility to fluconazole; 0.5, 0.5, 0.06, and 0.12 μg/ml, respectively, for C. tropicalis; and 0.004, 0.015, 0.008, and 0.03 μg/ml, respectively, forC. kefyr. GM 222712 and GM 237354 were the most active compounds against C. glabrata, C. parapsilosis, and Cryptococcus neoformans. AgainstC. glabrata and C. parapsilosis, the MIC90s of GM 222712 and GM 237354 were 0.5 and 4 μg/ml and 1 and 16 μg/ml, respectively. The MIC90s of GM 222712 and GM 237354 againstCryptococcus neoformans were 0.5 and 0.25 μg/ml, respectively. GM 193663, GM 211676, GM 222712, and GM 237354 were extremely active against P. carinii. The efficacies of sordarin derivatives against this organism were determined by measuring the inhibition of the uptake and incorporation of radiolabelled methionine into newly synthesized proteins. All compounds tested showed 50% inhibitory concentrations of <0.008 μg/ml. Against A. flavus and A. fumigatus, the MIC90s of GM 222712 and GM 237354 were 1 and 32 μg/ml and 32 and >64 μg/ml, respectively. In addition, GM 237354 was tested against the most important emerging fungal pathogens which affect immunocompromised patients. Cladosporium carrioni, Pseudallescheria boydii, and the yeast-like fungi Blastoschizomyces capitatus and Geotrichum clavatum were the most susceptible of the fungi to GM 237354, with MICs ranging from ≤0.25 to 2 μg/ml. The MICs of GM 237354 against Trichosporon beigelii and the zygomycetesAbsidia corymbifera, Cunninghamella bertholletiae, and Rhizopus arrhizus ranged from ≤0.25 to 8 μg/ml. Against dermatophytes, GM 237354 MICs were ≥2 μg/ml. In summary, we concluded that some sordarin derivatives, such as GM 222712 and GM 237354, showed excellent in vitro activities against a wide range of pathogenic fungi, includingCandida spp., Cryptococcus neoformans, P. carinii, and some filamentous fungi and emerging invasive fungal pathogens.

scholarly journals Recurrent candidaemia in a neonate with Hirschsprung's disease: fluconazole resistance and genetic relatedness of eight Candida tropicalis isolates

2006 ◽  
Vol 55 (4) ◽  
pp. 423-428 ◽  
Author(s):  
Pei Pei Chong ◽  
David Ching-Soo Chieng ◽  
Lee Yean Low ◽  
Asma Hafeez ◽  
Mariana Nor Shamsudin ◽  
...  
Keyword(s):  
Candida Tropicalis ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Genetic Relatedness ◽  
Infectious Agent ◽  
Venous Catheter ◽  
Drug Susceptibility ◽  
Fluconazole Resistant ◽  
Susceptibility Tests

The incidence of candidaemia among immunocompromised patients in Malaysia is increasing at an alarming rate. Isolation of clinical strains that are resistant to fluconazole has also risen markedly. We report here the repeated isolation of Candida tropicalis from the blood of a neonatal patient with Hirschsprung's disease. In vitro fluconazole susceptibility tests of the eight isolates obtained at different time points showed that seven of the isolates were resistant and one isolate was scored as susceptible dose-dependent. Random amplification of polymorphic DNA fingerprinting of the isolates using three primers and subsequent phylogenetic analysis revealed that these isolates were highly similar strains having minor genetic divergence, with a mean pairwise similarity coefficient of 0·893±0·041. The source of the infectious agent was thought to be the central venous catheter, as culture of its tip produced fluconazole-resistant C. tropicalis. This study demonstrates the utility of applying molecular epidemiology techniques to complement traditional mycological culture and drug susceptibility tests for accurate and appropriate management of recurrent candidaemia and highlights the need for newer antifungals that can combat the emergence of fluconazole-resistant C. tropicalis strains.

scholarly journals Morphological and Molecular Diversity of Ginger (Zingiber officinale Roscoe) Pathogenic Fungi in Chilga District, North Gondar, Ethiopia

2022 ◽  
Vol 2 ◽  
Author(s):  
Sefinew Tilahun ◽  
Marye Alemu ◽  
Mesfin Tsegaw ◽  
Nega Berhane
Keyword(s):  
Causative Agent ◽  
Fungal Pathogens ◽  
Pathogenic Fungus ◽  
Management Strategies ◽  
Infected Plant ◽  
Pathogenic Fungi ◽  
Zingiber Officinale ◽  
Morphological Characterization ◽  
Molecular Techniques ◽  
Diseased Plant

Ginger diseases caused by fungal pathogens have become one of the most serious problems causing reduced production around the world. It has also caused a major problem among farmers in different parts of Ethiopia resulting in a huge decline in rhizome yield. However, the exact causative agents of this disease have not been identified in the state. Although there are few studies related to pathogenic fungus identification, molecular level identification of fungal pathogen was not done in the area. Therefore, this study was undertaken to isolate and characterized the fungal causative agent of ginger disease from the diseased plant and the soil samples collected around the diseased plant from Chilga district, Gondar, Ethiopia. Samples from infected ginger plants and the soil around the infected plant were collected. Culturing and purification of isolates were made using Potato Dextrose Agar supplemented with antibacterial agent chloramphenicol. The morphological characterization was done by structural identification of the isolates under the microscope using lactophenol cotton blue stains. Isolated fungi were cultured and molecular identification was done using an internal transcribed spacer (ITS) of ribosomal DNA (rDNA). A total of 15 fungal morphotypes including 11 Aspergillus spp. (73.3%), 2 Penicillium spp. (13.3%), and single uncultured fungus clone S23 were isolated from the samples representing all the plant organs and the soil. Aspergillus spp. (73.3%) was the most common and seems to be the major causative agent. To the best of our knowledge, this is the first report of ginger pathogenic fungi in Ethiopia identified using ITS rDNA molecular techniques. This study will lay foundation for the development of management strategies for fungal diseases infecting ginger.

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