scholarly journals Candidalysin: From Mechanism of Action to Biomarker Development and Therapeutic Response

2020 ◽  
Author(s):  
Yao-Qi Chen ◽  
Qian Li ◽  
Tian-Yi Zhang ◽  
Ning-Ning Liu
Keyword(s):  
Host Defense ◽  
Fungal Pathogens ◽  
Therapeutic Response ◽  
Fungal Infections ◽  
Specific Gene ◽  
Clinical Settings ◽  
Diagnostic Biomarker ◽  
Systemic Fungal Infection ◽  
The World ◽  
Peptide Toxin

ABSTRACT The incidence of systemic fungal infection is increasing, and millions of people around the world suffer from fungal infections. Candida albicans is one of the most frequently isolated fungal pathogens in clinical settings. As a polymorphic organism, the transition between yeast and hyphae is critical for C. albicans virulence and pathogenesis. However, the mechanism of hyphae-associated virulence remains unclear. Candidalysin is the first human fungal cytolytic peptide toxin originating from the hyphae-specific gene, ECE1. This review will summarize the most recent progress underlying candidalysin-mediated epithelial damage and host defense pathways, which might shed new light on the development of a novel antifungal strategy and early diagnostic biomarker.

scholarly journals Recent advances in understanding inherited deficiencies in immunity to infections

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 243 ◽  
Author(s):  
Gregory M. Constantine ◽  
Michail S. Lionakis
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Fungal Infections ◽  
Microbial Pathogens ◽  
Host Immune Responses ◽  
Vaccination Strategies ◽  
The World ◽  
Human Immunity ◽  
Immune Pathways ◽  
Resistance To Infection

The immune system is central to our interactions with the world in which we live and importantly dictates our response to potential allergens, toxins, and pathogens to which we are constantly exposed. Understanding the mechanisms that underlie protective host immune responses against microbial pathogens is vital for the development of improved treatment and vaccination strategies against infections. To that end, inherited immunodeficiencies that manifest with susceptibility to bacterial, viral, and/or fungal infections have provided fundamental insights into the indispensable contribution of key immune pathways in host defense against various pathogens. In this mini-review, we summarize the findings from a series of recent publications in which inherited immunodeficiencies have helped illuminate the interplay of human immunity and resistance to infection.

scholarly journals Visible Lights Combined with Photosensitizing Compounds Are Effective against Candida albicans Biofilms

2021 ◽  
Vol 9 (3) ◽  
pp. 500 ◽  
Author(s):  
Priyanka Bapat ◽  
Gurbinder Singh ◽  
Clarissa J. Nobile
Keyword(s):  
Candida Albicans ◽  
Photodynamic Therapy ◽  
Biofilm Formation ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Therapeutic Strategies ◽  
Antifungal Drugs ◽  
Clinical Settings ◽  
Drug Resistant ◽  
Candida Albicans Biofilms

Fungal infections are increasing in prevalence worldwide, especially in immunocompromised individuals. Given the emergence of drug-resistant fungi and the fact that there are only three major classes of antifungal drugs available to treat invasive fungal infections, there is a need to develop alternative therapeutic strategies effective against fungal infections. Candida albicans is a commensal of the human microbiota that is also one of the most common fungal pathogens isolated from clinical settings. C. albicans possesses several virulence traits that contribute to its pathogenicity, including the ability to form drug-resistant biofilms, which can make C. albicans infections particularly challenging to treat. Here, we explored red, green, and blue visible lights alone and in combination with common photosensitizing compounds for their efficacies at inhibiting and disrupting C. albicans biofilms. We found that blue light inhibited biofilm formation and disrupted mature biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential. Red and green lights, however, inhibited biofilm formation only in combination with photosensitizing compounds but had no effects on disrupting mature biofilms. Taken together, these results suggest that photodynamic therapy may be an effective non-drug treatment for fungal biofilm infections that is worthy of further exploration.

scholarly journals Host Defence to Pulmonary Mycosis

1999 ◽  
Vol 10 (2) ◽  
pp. 147-155 ◽  
Author(s):  
Christopher H Mody ◽  
Peter W Warren
Keyword(s):  
Host Defense ◽  
Defense Mechanisms ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Data Extraction ◽  
Pathogenic Fungi ◽  
Fungal Disease ◽  
Medline Search ◽  
Pulmonary Mycosis ◽  
Immune Defects

OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.DATA SOURCES: English articles from 1966 to present were identified from a MEDLINE search.STUDY SELECTION: Articles were identified by a MEDLINE search of ‘exp lung/’ or ‘exp lung diseases/’ and ‘exp fungi/’. The titles and abstracts were screened to identify articles that contained salient information pertaining to host defense of respiratory mycoses.DATA EXTRACTION: Information was summarized from the articles pertaining to host defense of pulmonary mycosis that had been identified by the MEDLINE search.DATA SYNTHESIS: Fungi represent a unique and highly diverse group of pathogenic organisms that have become an increasingly prevalent cause of life-threatening illness. A worldwide increase in persons with immunodeficiency has been a major contributing factor to the increase in fungal disease. As a result, clinicians are faced with an expanding array of fungal infections that pose diagnostic and therapeutic challenges. The respiratory tract is the route of acquisition for many important fungal infections; thus, understanding the host defense in the lung is an essential component of understanding host defense to fungal disease. With this understanding, fungi may be divided on the basis of the predilection of certain mycosis for specific immune defects.CONCLUSIONS: By separating fungi based on the host immune defects that predispose to disease, in conjunction with traditional divisions based on the geographic distribution of fungi, clinicians are able to focus their diagnostic efforts and to identify fungal pathogens better. In addition, an understanding of the normal host defense mechanisms that serve to control fungal infections is essential to the development of novel antifungal therapies.

scholarly journals Commercial Essential Oil Combinations against Topical Fungal Pathogens

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400 ◽  
Author(s):  
Ané Orchard ◽  
Sandy F. van Vuuren ◽  
Alvaro M. Viljoen
Keyword(s):  
Essential Oil ◽  
Essential Oils ◽  
Fungal Pathogens ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Trichophyton Mentagrophytes ◽  
Clinical Settings ◽  
Synergistic Interactions ◽  
The Mean ◽  
Reference Strains

Essential oils are amongst the most popular natural products recommended for the treatment of topical fungal infections. This study investigated the antifungal activity of 128 essential oil combinations against fungal pathogen reference strains using the broth microdilution technique to determine the minimum inhibitory concentration (MIC). The essential oils were investigated at a volume of 100 μL and the combinations comprised of 50:50 μL. Each combination was tested in triplicate and the mean recorded. The fractional inhibitory concentration index was calculated for combinations, and synergistic interactions were investigated further at different ratios and plotted on isobolograms. The fungal pathogens were found to be highly susceptible to the essential oil combinations, with Trichophyton mentagrophytes being inhibited by all but one combination. The essential oil combinations containing Cinnamomum verum or Santalum austrocaledonicum were found to display the strongest inhibition with MIC values as low as 0.06 mg/mL. Potential combinations against fungal pathogens have been presented that could be studied in clinical settings with the goal of decreasing the need for systemic or prolonged antifungal treatments that may result in treatment failure or resistance.

scholarly journals The Ubiquitin-Modifying Enzyme A20 Terminates C-Type Lectin Receptor Signals and Is a Suppressor of Host Defense against Systemic Fungal Infection

2020 ◽  
Vol 88 (9) ◽  
Author(s):  
Jie Liang ◽  
Junyi J. Zhang ◽  
Hsin-I Huang ◽  
Masashi Kanayama ◽  
Nourhan Youssef ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Host Defense ◽  
Fungal Pathogens ◽  
Negative Regulator ◽  
Lectin Receptors ◽  
Systemic Fungal Infection ◽  
Content Type ◽  
Lectin Receptor ◽  
Editing Enzyme

ABSTRACT C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-κB is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-κB could profoundly influence host defense against fungal pathogens. However, little is known about the mechanisms that negatively regulate CLR-induced NF-κB, and molecules which act on the CLR family broadly and which directly regulate acute CLR-signaling cascades remain unidentified. Here, we identify the ubiquitin-editing enzyme A20 as a negative regulator of acute NF-κB activation downstream of multiple CLR pathways. Absence of A20 suppression results in exaggerated CLR responses in cells which are A20 deficient and also cells which are A20 haplosufficient, including multiple primary immune cells. Loss of a single allele of A20 results in enhanced defense against systemic Candida albicans infection and prolonged host survival. Thus, A20 restricts CLR-induced innate immune responses in vivo and is a suppressor of host defense against systemic fungal infection.

scholarly journals Host Defense Peptides as Templates for Antifungal Drug Development

2020 ◽  
Vol 6 (4) ◽  
pp. 241
Author(s):  
Virginia Basso ◽  
Dat Q. Tran ◽  
André J. Ouellette ◽  
Michael E. Selsted
Keyword(s):  
Host Defense ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Host Defense Peptides ◽  
Invasive Fungal Diseases ◽  
Defense Peptides

Current treatment for invasive fungal diseases is limited to three classes of antifungal drugs: azoles, polyenes, and echinocandins. The most recently introduced antifungal class, the echinocandins, was first approved nearly 30 years ago. The limited antifungal drug portfolio is rapidly losing its clinical utility due to the inexorable rise in the incidence of invasive fungal infections and the emergence of multidrug resistant (MDR) fungal pathogens. New antifungal therapeutic agents and novel approaches are desperately needed. Here, we detail attempts to exploit the antifungal and immunoregulatory properties of host defense peptides (HDPs) in the design and evaluation of new antifungal therapeutics and discuss historical limitations and recent advances in this quest.

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 Virus Infection of Aspergillus fumigatus Compromises the Fungus in Intermicrobial Competition

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 686
Author(s):  
Hasan Nazik ◽  
Ioly Kotta-Loizou ◽  
Gabriele Sass ◽  
Robert H. A. Coutts ◽  
David A. Stevens
Keyword(s):  
Virus Infection ◽  
Aspergillus Fumigatus ◽  
Stress Responses ◽  
Fungal Pathogens ◽  
Clinical Settings ◽  
Virus Infections ◽  
Fungal Strains ◽  
Common Reference ◽  
Strain Virus ◽  
Free Strain

Aspergillus and Pseudomonas compete in nature, and are the commonest bacterial and fungal pathogens in some clinical settings, such as the cystic fibrosis lung. Virus infections of fungi occur naturally. Effects on fungal physiology need delineation. A common reference Aspergillus fumigatus strain, long studied in two (of many) laboratories, was found infected with the AfuPmV-1 virus. One isolate was cured of virus, producing a virus-free strain. Virus from the infected strain was purified and used to re-infect three subcultures of the virus-free fungus, producing six fungal strains, otherwise isogenic. They were studied in intermicrobial competition with Pseudomonasaeruginosa. Pseudomonas culture filtrates inhibited forming or preformed Aspergillus biofilm from infected strains to a greater extent, also seen when Pseudomonas volatiles were assayed on Aspergillus. Purified iron-chelating Pseudomonas molecules, known inhibitors of Aspergillus biofilm, reproduced these differences. Iron, a stimulus of Aspergillus, enhanced the virus-free fungus, compared to infected. All infected fungal strains behaved similarly in assays. We show an important consequence of virus infection, a weakening in intermicrobial competition. Viral infection may affect the outcome of bacterial–fungal competition in nature and patients. We suggest that this occurs via alteration in fungal stress responses, the mechanism best delineated here is a result of virus-induced altered Aspergillus iron metabolism.

scholarly journals Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

2021 ◽  
Vol 7 (2) ◽  
pp. 124
Author(s):  
Charmaine Retanal ◽  
Brianna Ball ◽  
Jennifer Geddes-McAlister
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Treatment Options ◽  
Global Scale ◽  
Host Cells ◽  
Candida Spp ◽  
Post Translational Modifications ◽  
Fungal Host ◽  
Resistant Species

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.

In vitro evaluation of the anti-mycobacterial properties of the extracts of Momordica Charantia

2021 ◽  
Vol 16 (7) ◽  
pp. 15-22
Author(s):  
Paul Giftson ◽  
Jerrine Joseph ◽  
Revathy Kalyanasundaram ◽  
V. Ramesh Kumar ◽  
Wilson Aruni
Keyword(s):  
Medicinal Plants ◽  
Fungal Pathogens ◽  
Communicable Disease ◽  
Antimycobacterial Activity ◽  
Bitter Gourd ◽  
World Population ◽  
Methanol Extracts ◽  
Crude Extracts ◽  
The World

Tuberculosis (TB) is a communicable disease and remains one of the top 10 causes of death worldwide. One fourth of the world population is infected with TB at a risk of developing disease. The increase in the incidence of drug resistant TB around the world urges the need to develop a new candidate to fight against the disease. Plants were considered as the rich source of bioactive components to be used as potential drugs. Medicinal plants are used in pure as well as crude materials for their medicinal properties. Our research aims in identifying the phyto-molecules which have anti- tuberculosis property. Four medicinal plants namely, Acalyphaciliata (Kuppaimeni), Solanumtrilobatum (Thuthuvalai), Momordicacharantia (Bitter Gourd) and Sennaauriculata (Avaram) were chosen to evaluate their antimicrobial activity focusing on anti-tubercular activity. The methanol extracts of the medicinal plants showed significant inhibitory activity against bacterial and fungal pathogens. Sennaauriculata methanol extracts showed activity against S. aureus, E. coli, P. aeruginosa and C. albicans. In the screening of antimycobacterial activity done by LRP assay, among the plant extracts tested, the hexane crude extracts of Momordicacharantia (Bitter Gourd) showed 82.2% and 81.03% of inhibition against M. tuberculosis H37Rv at 500µg/ml and 250µg/ml concentration respectively. Similarly, the methanol crude extracts of Momordicacharantia showed 87.14% and 63.55% of inhibition at 500µg/ml and 250µg/ml concentration respectively.

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