Neutrophil and Eosinophil DNA Extracellular Trap Formation: Lessons From Pathogenic Fungi

Fungal infections represent a worldwide health problem. Fungal pathogens are responsible for a variety of conditions, including superficial diseases, allergic pathologies and potentially lethal invasive infections. Neutrophils and eosinophils have been implicated as effector cells in several pathologies. Neutrophils are major effector cells involved in the control of fungal infections and exhibit a plethora of antifungal mechanisms, such as phagocytosis, reactive oxygen species production, degranulation, extracellular vesicle formation, and DNA extracellular trap (ET) release. Eosinophils are polymorphonuclear cells classically implicated as effector cells in the pathogenesis of allergic diseases and helminthic infections, although their roles as immunomodulatory players in both innate and adaptive immunity are currently recognized. Eosinophils are also endowed with antifungal activities and are abundantly found in allergic conditions associated with fungal colonization and sensitization. Neutrophils and eosinophils have been demonstrated to release their nuclear and mitochondrial DNA in response to many pathogens and pro-inflammatory stimuli. ETs have been implicated in the killing and control of many pathogens, as well as in promoting inflammation and tissue damage. The formation of ETs by neutrophils and eosinophils has been described in response to pathogenic fungi. Here, we provide an overview of the mechanisms involved in the release of neutrophil and eosinophil ETs in response to fungal pathogens. General implications for understanding the formation of ETs and the roles of ETs in fungal infections are discussed.

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The Mechanisms of Mating in Pathogenic Fungi—A Plastic Trait

Genes ◽

10.3390/genes10100831 ◽

2019 ◽

Vol 10 (10) ◽

pp. 831

Author(s):

Jane Usher

Keyword(s):

Fungal Pathogens ◽

Crop Yields ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Yeast Saccharomyces Cerevisiae ◽

Closely Related Species ◽

Sexual And Asexual Reproduction ◽

Target Dna ◽

High Degree ◽

The Impact

The impact of fungi on human and plant health is an ever-increasing issue. Recent studies have estimated that human fungal infections result in an excess of one million deaths per year and plant fungal infections resulting in the loss of crop yields worth approximately 200 million per annum. Sexual reproduction in these economically important fungi has evolved in response to the environmental stresses encountered by the pathogens as a method to target DNA damage. Meiosis is integral to this process, through increasing diversity through recombination. Mating and meiosis have been extensively studied in the model yeast Saccharomyces cerevisiae, highlighting that these mechanisms have diverged even between apparently closely related species. To further examine this, this review will inspect these mechanisms in emerging important fungal pathogens, such as Candida, Aspergillus, and Cryptococcus. It shows that both sexual and asexual reproduction in these fungi demonstrate a high degree of plasticity.

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A novel glyco-conjugate vaccine against fungal pathogens

Journal of Experimental Medicine ◽

10.1084/jem.20050749 ◽

2005 ◽

Vol 202 (5) ◽

pp. 597-606 ◽

Cited By ~ 311

Author(s):

Antonella Torosantucci ◽

Carla Bromuro ◽

Paola Chiani ◽

Flavia De Bernardis ◽

Francesco Berti ◽

...

Keyword(s):

Conjugate Vaccine ◽

Fungal Pathogens ◽

Pathogenic Fungi ◽

Immune Serum ◽

Vaginal Fluid ◽

Vaginal Infections ◽

Lethal Challenge ◽

Immune Effector ◽

Effector Cells

To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic β-glucan preparation from the brown alga Laminaria digitata, with the diphtheria toxoid CRM197, a carrier protein used in some glyco-conjugate bacterial vaccines. This Lam-CRM conjugate proved to be immunogenic and protective as immunoprophylactic vaccine against both systemic and mucosal (vaginal) infections by Candida albicans. Protection probably was mediated by anti-β-glucan antibodies as demonstrated by passive transfer of protection to naive mice by the whole immune serum, the immune vaginal fluid, and the affinity-purified anti-β-glucan IgG fractions, as well as by administration of a β-glucan–directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or β-glucan particles before transfer. Anti-β-glucan antibodies bound to C. albicans hyphae and inhibited their growth in vitro in the absence of immune-effector cells. Remarkably, Lam-CRM–vaccinated mice also were protected from a lethal challenge with conidia of Aspergillus fumigatus, and their serum also bound to and markedly inhibited the growth of A. fumigatus hyphae. Thus, this novel conjugate vaccine can efficiently immunize and protect against two major fungal pathogens by mechanisms that may include direct antifungal properties of anti-β-glucan antibodies.

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Advances in Fungal Peptide Vaccines

Journal of Fungi ◽

10.3390/jof6030119 ◽

2020 ◽

Vol 6 (3) ◽

pp. 119 ◽

Cited By ~ 2

Author(s):

Leandro B. R. Da Silva ◽

Carlos P. Taborda ◽

Joshua D. Nosanchuk

Keyword(s):

Fungal Pathogens ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Effective Vaccine ◽

Past Century ◽

Mortality And Morbidity ◽

Bioinformatic Tools ◽

The Past ◽

New Methodologies

Vaccination is one of the greatest public health achievements in the past century, protecting and improving the quality of life of the population worldwide. However, a safe and effective vaccine for therapeutic or prophylactic treatment of fungal infections is not yet available. The lack of a vaccine for fungi is a problem of increasing importance as the incidence of diverse species, including Paracoccidioides, Aspergillus, Candida, Sporothrix, and Coccidioides, has increased in recent decades and new drug-resistant pathogenic fungi are emerging. In fact, our antifungal armamentarium too frequently fails to effectively control or cure mycoses, leading to high rates of mortality and morbidity. With this in mind, many groups are working towards identifying effective and safe vaccines for fungal pathogens, with a particular focus of generating vaccines that will work in individuals with compromised immunity who bear the major burden of infections from these microbes. In this review, we detail advances in the development of vaccines for pathogenic fungi, and highlight new methodologies using immunoproteomic techniques and bioinformatic tools that have led to new vaccine formulations, like peptide-based vaccines.

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Host Defence to Pulmonary Mycosis

Canadian Journal of Infectious Diseases ◽

10.1155/1999/139326 ◽

1999 ◽

Vol 10 (2) ◽

pp. 147-155 ◽

Cited By ~ 3

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.

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Biosensors for Fungal Detection

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.4.02 ◽

2021 ◽

Author(s):

Hamdi Nsairat ◽

Areej M. Jaber ◽

Mazen Al-Sulaibi

Keyword(s):

Molecular Diagnosis ◽

Diagnostic Tests ◽

Fungal Pathogens ◽

Pathogen Detection ◽

Drug Sensitivity ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Chain Reactions ◽

Polymerase Chain Reactions ◽

Polymerase Chain

Due to the serious threat of invasive fungal infections, there is an emergent need for improved a sensitive and more accurate diagnostic tests for detection of systemic pathogenic fungi and plant health. Traditional fungal diagnosis can only be achieved at later growing phases. The complex and difficult immunodiagnostic is also widely employed. Enzyme-based immunoassays which lead to cross-interaction with different fungi still also obeyed. A polymerase chain reactions (PCRs)- based molecular diagnosis are does not enable precise identification of fungal pathogens, or the ability to test isolates for drug sensitivity. In the future, biosensing technologies and nanotechnological tools, will improve diagnosis of pathogenic fungi through a specific and sensitive pathogen detection. This report systematically reviews the most prominent biosensor trends for fungi detection.

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Molecular Diagnosis of Invasive Fungal Infections: Species Identification and Quantitative Analysis by Broad-Spectrum PCR Assays.

Blood ◽

10.1182/blood.v106.11.5339.5339 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5339-5339

Author(s):

Lenka Baskova ◽

Sandra Preuner ◽

Thomas Lion

Keyword(s):

Quantitative Analysis ◽

Dna Sequences ◽

Fungal Pathogens ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Fungal Species ◽

Invasive Fungal Infections ◽

Fungal Genome ◽

Quantitative Detection ◽

Correct Identification

Abstract Invasive fungal infections (IFI) play an increasingly important role as life-threatening complications in immunocompromised patients. Early application of antimycotic agents is an essential prerequisite for successful therapy. However, standardized diagnostic techniques permitting rapid, sensitive and, no less importantly, economic screening for the clinically relevant fungi have been lacking. We have developed two different real-time PCR systems for quantitative analysis of pathogenic fungi. The Pan-AC assay* permits in a single reaction the detection of all important Aspergillus and Candida species, which are responsible for the great majority of IFI in immunosuppressed individuals. In view of the increasing incidence of invasive infections caused by hitherto uncommon fungal species, new diagnostic tests with very broad specificity are required. We have therefore developed an additional two-reaction Pan-fungus assay*, which facilitates quantitative detection of a wide spectrum of fungal species (n>50), including also the newly emerging pathogenic fungi. The assays display high sensitivity and show no cross-reactivity with non-fungal pathogens or human DNA sequences. We have established an additional rapid molecular assay based on PCR fragment length analysis of a variable region in the fungal genome permitting rapid identification of the fungal species present, in order to facilitate selection of the most appropriate antifungal treatment. Correct identification of specific fungal pathogens including different Aspergillus, Candida and Fusarium species detected by the above assays in patients with febrile neutropenia has been confirmed by sequence analysis. The new assays are readily applicable to routine clinical diagnosis and provide a rapid and economic approach to the screening and monitoring of invasive fungal infections.

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Carrier-Mediated Drug Uptake in Fungal Pathogens

Genes ◽

10.3390/genes11111324 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1324

Author(s):

Mónica Galocha ◽

Inês Vieira Costa ◽

Miguel Cacho Teixeira

Keyword(s):

Drug Resistance ◽

Fungal Pathogens ◽

Fungal Infections ◽

Current Knowledge ◽

Pathogenic Fungi ◽

Resistance Mechanisms ◽

Antifungal Drugs ◽

Major Facilitator Superfamily ◽

Drug Uptake ◽

Human Pathogens

Candida, Aspergillus, and Cryptococcus species are the most frequent cause of severe human fungal infections. Clinically relevant antifungal drugs are scarce, and their effectiveness are hampered by the ability of fungal cells to develop drug resistance mechanisms. Drug effectiveness and drug resistance in human pathogens is very often affected by their “transportome”. Many studies have covered a panoply of drug resistance mechanisms that depend on drug efflux pumps belonging to the ATP-Binding Cassette and Major Facilitator Superfamily. However, the study of drug uptake mechanisms has been, to some extent, overlooked in pathogenic fungi. This review focuses on discussing current knowledge on drug uptake systems in fungal pathogens, highlighting the need for further studies on this topic of great importance. The following subjects are covered: (i) drugs imported by known transporter(s) in pathogenic fungi; and (ii) drugs imported by known transporter(s) in the model yeast Saccharomyces cerevisiae or in human parasites, aimed at the identification of their homologs in pathogenic fungi. Besides its contribution to increase the understanding of drug-pathogen interactions, the practical implications of identifying drug importers in human pathogens are discussed, particularly focusing on drug development strategies.

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Alteration of Termite Locomotion and Allogrooming in Response to Infection by Pathogenic Fungi

Journal of Economic Entomology ◽

10.1093/jee/toab071 ◽

2021 ◽

Author(s):

Ali Hassan ◽

Qiuying Huang ◽

Nasir Mehmood ◽

Huan Xu ◽

Wei Zhou ◽

...

Keyword(s):

Metarhizium Anisopliae ◽

Fungal Pathogens ◽

Fungal Infections ◽

Pathogenic Fungi ◽

Hygienic Behavior ◽

Termite Species ◽

Low Concentrations ◽

Living Together ◽

High Concentrations ◽

Number Of Individuals

Abstract Termites, being vulnerable to parasitic or pathogenic infections due to large number of individuals living together in colonies, have evolved various behavioral and physiological tactics to resist the infections by those pathogens. Locomotion can help termites collect information on parasites and accordingly exhibit hygienic behaviors. Termites inevitably encounter entomopathogenic fungi during nesting and foraging. However, how these fungal pathogens influence locomotion of termites and how hygienic behavior benefits their survival remains unknown. Here, we examined locomotion alteration of the termite Reticulitermes chinensis (Isoptera: Rhinotermitidae) after infections with different concentrations of the entomopathogenic fungus Metarhizium anisopliae (Hypocreales: Clavicipitaceae). When R. chinensis was isolated, the low concentration (5 × 103 conidia/ml) significantly increased termite locomotion after 6, 12, and 24 h compared with control. However, the high concentrations (5 × 107, 5 × 109 conidia/ml) significantly decreased termite locomotion after 48 h, and termite survival was also significantly lower at 5 × 107 and 5 × 109 conidia/ml compared with the low concentrations and the control. When R. chinensis was in group, however, the locomotion significantly increased 24 h after exposure to 5 × 103 and 5 × 109 conidia/ml but was normalized after 48 h of exposure compared with the control. Allogrooming was significantly higher at 5 × 103 and 5 × 109 conidia/ml compared with the control. The fungal infection did not result in significantly higher mortality of the group termites probably owing to their allogrooming. These findings enhance our understanding on how a termite species copes with biotic stress (i.e., fungal infections) via adaptive behaviors.

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A Nanoemulsion as an Effective Treatment Against Human Pathogenic Fungi

10.1101/737767 ◽

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.

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Optimization of an Infected Shoe Model for the Evaluation of an Ultraviolet Shoe Sanitizer Device

Journal of the American Podiatric Medical Association ◽

10.7547/1020309 ◽

2012 ◽

Vol 102 (4) ◽

pp. 309-313 ◽

Cited By ~ 19

Author(s):

Mahmoud A. Ghannoum ◽

Nancy Isham ◽

Lisa Long

Keyword(s):

Fungal Infections ◽

Effective Means ◽

Pathogenic Fungi ◽

Trichophyton Mentagrophytes ◽

Fungal Colonization ◽

Colony Forming Units ◽

Fungal Organisms ◽

Vitro Model ◽

Ultraviolet Treatment

Background: Onychomycosis and tinea pedis (athlete’s foot) are infections of the nails and skin caused by pathogenic fungi collectively known as dermatophytes. These infections are difficult to treat, and patients often relapse; it is thought that a patient’s footwear becomes infected with these fungal organisms and, thus, is an important reservoir for reinfection. Therefore, it is important to find an effective means for killing the dermatophytes that may have colonized the inner surface of the shoes of patients with superficial fungal infections. In this study, we developed an in vitro model for culturing dermatophytes in footwear and used this model to evaluate the effectiveness of a commercial ultraviolet shoe sanitizer in eradicating the fungal elements residing in shoes. Methods: Leather and athletic shoes (24 pairs) were inoculated with either Trichophyton rubrum or Trichophyton mentagrophytes (107 colony-forming units/mL) strains and were placed at 35°C for 4 to 5 days. Next, we compared the ability of swabbing versus scraping to collect microorganisms from infected shoes. Following the optimized method, shoes were infected and were irradiated with one to three cycles of radiation. The inner surfaces of the shoes were swabbed or scraped, and the specimens were cultured for dermatophyte colony-forming units. Results: Leather and canvas shoes were infected to the same extent. Moreover, scraping with a scalpel was overall more effective than was swabbing with a cotton-tipped applicator in recovering viable fungal elements. Irradiation of shoes with one, two, or three cycles resulted in reduction of fungal colonization to the same extent. Conclusions: The developed infected shoe model is useful for assessing the effectiveness of ultraviolet shoe sanitizers. Also, ultraviolet treatment of shoes with a commercial ultraviolet C sanitizing device was effective in reducing the fungal burden in shoes. These findings have implications regarding breaking foot infection cycles. (J Am Podiatr Med Assoc 102(4): 309–313, 2012)

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