scholarly journals ETIOLOGICAL AGENTS OF FUNGAL INFECTIONS IN PATIENTS AFTER SOLID ORGAN TRANSPLANTATIONS (SOT) - FUNGAL STRAINS AND THEIR SUSCEPTIBILITY TO ANTIFUNGAL DRUGS.

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 396
Author(s):  
A Chmura ◽  
I Netsvyetayeva ◽  
E Swoboda-Kopec ◽  
D Kawecki ◽  
M Sikora ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Fungal Strains ◽  
Etiological Agents

scholarly journals Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

2021 ◽  
Vol 7 (6) ◽  
pp. 451
Author(s):  
Georgios Karavalakis ◽  
Evangelia Yannaki ◽  
Anastasia Papadopoulou
Keyword(s):  
Host Defense ◽  
Hematopoietic Cell Transplantation ◽  
State Of The Art ◽  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Immunocompromised Host ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Cell Immunotherapy ◽  
Life Threatening

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

scholarly journals Duplication and overexpression of the genes encoding a beta 1,3-glucan synthase confer the intrinsic resistance to echinocandin in Mucor circinelloides

2022 ◽  
Author(s):  
Soo Chan Lee ◽  
Alexis Garcia ◽  
Eun Young Huh
Keyword(s):  
Fungal Infections ◽  
Secondary Infection ◽  
Effective Means ◽  
Mucor Circinelloides ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Intrinsic Resistance ◽  
Glucan Synthase ◽  
Drug Classes ◽  
Genes Encoding

Procedures such as solid organ transplants and cancer treatments can leave many patients in an immunocompromised state resulting in an increased susceptibility to opportunistic diseases including fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients. Currently there has been a sharp increase in mucormycosis cases as a secondary infection in patients battling SARS-CoV-2 infections. Mucorales fungi are notorious for presenting resistance to most antifungal drugs. The absence of effective means to treat these infections results in mortality rates approaching 100% in cases of disseminated infection. One of the most effective antifungal drug classes currently available are echinocandins. Echinocandins seem to be efficacious in treatment of many other fungal infections. Unfortunately, susceptibility testing has found that echinocandins have no to little effect on Mucorales. In this study, we found that the model Mucorales Mucor circinelloides genome carries three copies of the genes encoding for the echinocandin target protein β-(1,3)-D-glucan synthase (fksA, fksB, and fksC). Interestingly, we revealed that exposing M. circinelloides to micafungin significantly increased the expression of the fksA and fksB genes when compared to an untreated control. We further uncovered that the serine/threonine phosphatase calcineurin is responsible for the overexpression of fksA and fksB as deletion of calcineurin results in a decrease in expression of all three fks genes and a lower minimal inhibitory concentration (MIC) to micafungin. Taken together, this study demonstrates that the fks gene duplication and overexpression by calcineurin contribute to the intrinsic resistance to echinocandins in Mucor.

Exploration of Medicinal Plants as Sources of Novel Anticandidal Drugs

2019 ◽  
Vol 19 (28) ◽  
pp. 2579-2592
Author(s):  
Ajay Kumar ◽  
Feroz Khan ◽  
Dharmendra Saikia
Keyword(s):  
Drug Resistance ◽  
Medicinal Plants ◽  
Fungal Infections ◽  
Relevant Information ◽  
Antifungal Drugs ◽  
Fungal Strains ◽  
Efficient Management ◽  
Mucosal Surfaces ◽  
Human Infections ◽  
Anti Fungal

Background: : Human infections associated with skin and mucosal surfaces, mainly in tropical and sub-tropical parts of the world. During the last decade, there have been an increasing numbers of cases of fungal infections in immunocompromised patients, coupled with an increase in the number of incidences of drug resistance and toxicity to anti fungal agents. Hence, there is a dire need for safe, potent and affordable new antifungal drugs for the efficient management of candidal infections with minimum or no side effects. Introduction: : Candidiasis represents a critical problem to human health and a serious concern worldwide. Due to the development of drug resistance, there is a need for new antifungal agents. Therefore, we reviewed the different medicinal plants as sources of novel anticandidal drugs. Methods: : The comprehensive and detailed literature on medicinal plants was carried out using different databases, such as Google Scholar, PubMed, and Science Direct and all the relevant information from the articles were analyzed and included. Result: : Relevant Publications up to the end of November 2018, reporting anticandidal activity of medicinal plants has been included in the present review. In the present study, we have reviewed in the light of SAR and mechanisms of action of those plants whose extracts or phytomolecules are active against candida strains. Conclusion:: This article reviewed natural anticandidal drugs of plant origin and also summarized the potent antifungal bioactivity against fungal strains. Besides, mechanism of action of these potent active plant molecules was also explored for a comparative study. We concluded that the studied active plant molecules exhibit potential antifungal activity against resistant fungal strains.

scholarly journals Nanoemulsion as an Effective Treatment against Human-Pathogenic Fungi

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Alexis Garcia ◽  
Yong Yi Fan ◽  
Sandeep Vellanki ◽  
Eun Young Huh ◽  
DiFernando Vanegas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Therapeutic Approaches ◽  
Content Type ◽  
New Therapeutic Approaches ◽  
Development Of Resistance

ABSTRACT Infections triggered by pathogenic fungi cause a serious threat to the public health care system. In particular, an increase of antifungal drug-resistant fungi has resulted in difficulty in treatment. 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 demonstrate the efficacy of the nanoemulsion NB-201, which utilizes the surfactant benzalkonium chloride, against human-pathogenic fungi. We found that NB-201 exhibited in vitro activity against Candida albicans, including both planktonic growth and biofilms. Furthermore, treatments with NB-201 significantly reduced the fungal burden at the infection site and presented an 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 developing, presenting a novel treatment to control fungal wound or skin infections. IMPORTANCE Advances in medicine have resulted in the discovery and implementation of treatments for human disease. While these recent advances have been beneficial, procedures such as solid-organ transplants and cancer treatments have left many patients in an immunocompromised state. Furthermore, the emergence of immunocompromising diseases such as HIV/AIDS or other immunosuppressive medical conditions have opened an opportunity for fungal infections to afflict patients globally. The development of drug resistance in human-pathogenic fungi and the limited array of antifungal drugs has left us in a scenario where we need to develop new therapeutic approaches to treat fungal infections that are less prone to the development of resistance by pathogenic fungi. The significance of our work lies in utilizing a novel nanoemulsion formulation to treat topical fungal infections while minimizing risks of drug resistance development.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  
Keyword(s):  
Schiff Base ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
Total Sterol ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Ergosterol Biosynthesis ◽  
Dependent Manner ◽  
Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

Synthesis and Biological Activity of 3-(substitutedphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine: Part II

2020 ◽  
Vol 18 ◽  
Author(s):  
Niranjan Kaushik ◽  
Nitin Kumar ◽  
Anoop Kumar ◽  
Vikas Sharma
Keyword(s):  
Antifungal Activity ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Mass Spectral Data ◽  
Triazole Derivatives ◽  
Mass Spectral ◽  
Fungal Strains ◽  
Antifungal Properties ◽  
Antifungal Potential ◽  
Spectral Data Analysis

Background: Fungal infections are opportunistic infections that become a serious problem to human health. Objective: Considering the antifungal potential of triazole nucleus, the study was carried out with the objective to synthesize some novel triazole derivatives with antifungal potential. Method: 1,2,4-triazole derivatives were synthesized via a two step reaction (reported earlier). The first step involves reaction of substituted benzoic acid with thiocarbohydrazide to form 4-amino-3-(substituted phenyl)-5-mercapto-1, 2, 4-triazole derivatives (1a-1k) while in second step, synthesized compounds (1a-1k) were then subsequently treated with substituted acetophenone to yield substituted (4-methoxyphenyl-7H-[1, 2, 4] triazolo [3, 4-b][1,3,4] thiadiazine derivatives (2a-2k). All synthesized compounds were characterized by IR, 1H NMR, and Mass spectral data analysis and were screened for their antifungal properties against different fungal strains i.e. Candida tropicalis (ATCC-13803, ATCC-20913), Candida albicans (ATCC-60193), Candida inconspicua (ATCC-16783) and Candida glabrata (ATCC-90030, ATCC-2001). Results: Compound 2d displayed better percentage inhibition (26.29%, 24.81%) than fluconazole (24.44%, 22.96%) against ATCC-16783, ATCC-2001 fungal strains respectively at 100µg/ml. Compound 2f also displayed better percentage inhibition (28.51%) against ATCC-90030 as compared to fluconazone (27.4%) at 200 µg/ml. Similarly, compounds 2e and 2j also exhibited better antifungal properties than fluconazole at 200µg/ml. Compound 2e was found most potent against ATCC13803 (30.37%) and ATCC-90030 (30.37%) fungal strains as compared to fluconazole (28.14%, 27.4%) at 200 µg/ml respectively whereas compound 2j exhibited better antifungal activity (28.51%) against ATCC-60193 than fluconazole (27.7%) at 200 µg/ml. Conclusion: The results were in accordance with our assertions for triazole derivatives, as all compounds displayed moderate to good antifungal activity.

scholarly journals Herbal Products and Their Active Constituents Used Alone and in Combination with Antifungal Drugs against Drug-Resistant Candida sp.

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 655
Author(s):  
Anna Herman ◽  
Andrzej Przemysław Herman
Keyword(s):  
Biofilm Formation ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Membrane Transporters ◽  
Drug Resistant ◽  
Herbal Products ◽  
Active Constituents ◽  
Over Expression ◽  
Candida Sp ◽  
Current State

Clinical isolates of Candida yeast are the most common cause of opportunistic fungal infections resistant to certain antifungal drugs. Therefore, it is necessary to detect more effective antifungal agents that would be successful in overcoming such infections. Among them are some herbal products and their active constituents.The purpose of this review is to summarize the current state of knowledge onherbal products and their active constituents havingantifungal activity against drug-resistant Candida sp. used alone and in combination with antifungal drugs.The possible mechanisms of their action on drug-resistant Candida sp. including (1) inhibition of budding yeast transformation into hyphae; (2) inhibition of biofilm formation; (3) inhibition of cell wall or cytoplasmic membrane biosynthesis; (4) ROS production; and (5) over-expression of membrane transporters will be also described.

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