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Fifty Years of Fungi: A Special Issue Honoring the Contributions...
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Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (20 October 2023) | Viewed by 25866

Special Issue Editor

Prof. Dr. Brian L. Wickes

E-Mail Website
Guest Editor
Department of Microbiology, Immunology, and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Interests: molecular diagnostics; fungal pathogenesis; Cryptococcus neoformans morphology and development; Candida glabrata and Candida auris drug resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Compared to other medically important pathogens, medical mycology is a relatively new field. In fact, Chester Emmons, the first US government medical mycologist, and arguably the father of medical mycology, was perhaps prescient in concluding that fungal infections were widespread and the fungi that caused these infections were ubiquitous. Unfortunately, this belief was confirmed shortly after AIDS became a mainstream infection, and later through more aggressive advances in modern medicine, including organ transplants and chemotherapy, which created patient populations highly susceptible to life-threatening fungal infections.

Kyung Joo (June) Kwon-Chung is a direct descendent of the Emmons lineage and if not the mother of medical mycology, she certainly is in the running for first lady. She joined the Medical Mycology Section of the NIAID Laboratory of Microbiology in 1966 as a visiting fellow under Emmons and eventually became a senior investigator in the NIAID Laboratory of Clinical Investigation in 1973. In 1995, she became the chief of the Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology. Prior to working with Emmons, she was a graduate student of Ken Raper at the University of Wisconsin. Raper was involved in early research on Penicillium strain improvement for the purposes of penicillin production, which was crucial to the war effort. Some of his strains are still used today. Her work with Raper centered on characterizing Aspergillus strains, which resulted in the discovery of many new species. Much of this work was included in Raper and Fennell’s monograph, The Genus Aspergillus, which is still an invaluable resource in spite of having been published 50 years ago. In a career that began in the early 1960s (and is still ongoing!) it is doubtful that any medical mycologist, past or present, can claim the breath of Dr. Kwon-Chung’s expertise. Although her early work with Raper put her on the path of classical mycology, she has published original research spanning topics from fungal identification and morphology to molecular mycology, and in diverse research areas ranging from new fungal species discovery and characterization, to genome sequencing. She was one of the founders, and continues to be an organizer of, the International Meeting on Cryptococcus and Cryptococcosis, which first met in Jerusalem, Israel in 1989.

Her career has resulted in her winning virtually every major award in the field of medical mycology, as well as numerous others, including the NIH Director's Award, the Korean Overseas Compatriots Prize for Science, the Medical Mycology's Rhoda Benham Award, a Lifetime Achievement Award from the American Society for Microbiology, the International Society of Human and Animal Mycology (ISHAM) Award, and the Lucille George’s Award given by the International Society of Human and Animal Mycology. She is well-known throughout the world with a reputation built in part, on the number of people she has trained in her laboratory and supported during their careers, both domestic and foreign.

The Journal of Fungi is pleased to announce a Special Issue honoring June Kwon-Chung for her outstanding contributions to medical mycology. Because of her broad publication record in the field, submissions can be on any topic relevant to medical mycology including, but not limited to, taxonomy, fungal identification, molecular biology, genetics, pathogenesis, and morphology.

Prof. Dr. Brian L. Wickes
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (14 papers)

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Research

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15 pages, 1195 KiB  
Article
Combination of Systemic and Lock-Therapies with Micafungin Eradicate Catheter-Based Biofilms and Infections Caused by Candida albicans and Candida parapsilosis in Neutropenic Rabbit Models
by Ruta Petraitiene, Vidmantas Petraitis, Myo H. Zaw, Kaiser Hussain, Rodolfo J. Ricart Arbona, Emanuel Roilides and Thomas J. Walsh
J. Fungi 2024, 10(4), 293; https://doi.org/10.3390/jof10040293 - 17 Apr 2024
Viewed by 409
Abstract
Vascular catheter-related infections, primarily caused by Candida albicans and Candida parapsilosis, pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate [...] Read more.
Vascular catheter-related infections, primarily caused by Candida albicans and Candida parapsilosis, pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 103 CFU/mL of C. albicans or C. parapsilosis, establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 104 to 1.8 × 102 CFU/mL of C. albicans and from 5.9 × 104 to 2.7 × 102 CFU/mL of C. parapsilosis (p ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of C. albicans from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) (p ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in C. parapsilosis in all treated tissues (p ≤ 0.05) except kidney. Serum (1→3)-β-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by C. albicans or C. parapsilosis, particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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16 pages, 4403 KiB  
Article
Ergosterol Is Critical for Sporogenesis in Cryptococcus neoformans
by Amber R. Matha, Xiaofeng Xie and Xiaorong Lin
J. Fungi 2024, 10(2), 106; https://doi.org/10.3390/jof10020106 - 26 Jan 2024
Viewed by 1141
Abstract
Microbes, both bacteria and fungi, produce spores to survive stressful conditions. Spores produced by the environmental fungal pathogen Cryptococcus neoformans serve as both surviving and infectious propagules. Because of their importance in disease transmission and pathogenesis, factors necessary for cryptococcal spore germination are [...] Read more.
Microbes, both bacteria and fungi, produce spores to survive stressful conditions. Spores produced by the environmental fungal pathogen Cryptococcus neoformans serve as both surviving and infectious propagules. Because of their importance in disease transmission and pathogenesis, factors necessary for cryptococcal spore germination are being actively investigated. However, little is known about nutrients critical for sporogenesis in this pathogen. Here, we found that ergosterol, the main sterol in fungal membranes, is enriched in spores relative to yeasts and hyphae. In C. neoformans, the ergosterol biosynthesis pathway (EBP) is upregulated by the transcription factor Sre1 in response to conditions that demand elevated ergosterol biosynthesis. Although the deletion of SRE1 enhances the production of mating hyphae, the sre1Δ strain is deficient at producing spores even when crossed with a wild-type partner. We found that the defect of the sre1Δ strain is specific to sporogenesis, not meiosis or basidium maturation preceding sporulation. Consistent with the idea that sporulation demands heightened ergosterol biosynthesis, EBP mutants are also defective in sporulation. We discovered that the overexpression of some EBP genes can largely rescue the sporulation defect of the sre1Δ strain. Collectively, we demonstrate that ergosterol is a critical component in cryptococcal preparation for sporulation. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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10 pages, 247 KiB  
Article
Antigenic Relatedness between Mannans from Coccidioides immitis and Coccidioides posadasii Spherules and Mycelia
by Amanda R. Burnham-Marusich, Kathleen R. Zayac, John N. Galgiani, Lourdes Lewis and Thomas R. Kozel
J. Fungi 2024, 10(2), 89; https://doi.org/10.3390/jof10020089 - 23 Jan 2024
Viewed by 1047
Abstract
Immunoassays for cell wall mannans that are excreted into serum and urine have been used as an aid in the diagnosis of many disseminated fungal infections, including coccidioidomycosis. Antigen-detection immunoassays are critically dependent on the detection of an analyte, such as mannan, by [...] Read more.
Immunoassays for cell wall mannans that are excreted into serum and urine have been used as an aid in the diagnosis of many disseminated fungal infections, including coccidioidomycosis. Antigen-detection immunoassays are critically dependent on the detection of an analyte, such as mannan, by antibodies that are specific to the analyte. The goal of this study was to evaluate the extent of cross-reactivity of polyclonal antibodies raised against Coccidioides spp. Analysis of antigenic relatedness between mannans from C. posadasii and C. immitis spherules and mycelia showed complete relatedness when evaluated by the method of Archetti and Horsfall, which was originally used to study the antigenic relationships between Influenzae virus isolates. In a further effort to validate the suitability of the antigenic relatedness calculation methodology for polysaccharide antigens, we also applied the method of Archetti and Horsfall to published results that had previously identified the major capsular serotypes of Cryptococcus species. The results of this analysis showed that Archetti and Horsfall’s antigenic relatedness calculation correctly identified the major cryptococcal serotypes. Together, these results suggest that the method is applicable to polysaccharide antigens, and that immunoassays that detect Coccidioides mannans are likely to have good reactivity across Coccidioides species (inclusivity) due to the species’ high level of antigenic relatedness. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
16 pages, 12425 KiB  
Article
SAGA Complex Subunit Hfi1 Is Important in the Stress Response and Pathogenesis of Cryptococcus neoformans
by Chendi K. Yu, Christina J. Stephenson, Tristan C. Villamor, Taylor G. Dyba, Benjamin L. Schulz and James A. Fraser
J. Fungi 2023, 9(12), 1198; https://doi.org/10.3390/jof9121198 - 15 Dec 2023
Viewed by 1119
Abstract
The Spt-Ada-Gcn Acetyltransferase (SAGA) complex is a highly conserved co-activator found across eukaryotes. It is composed of a number of modules which can vary between species, but all contain the core module. Hfi1 (known as TADA1 in Homo sapiens) is one of [...] Read more.
The Spt-Ada-Gcn Acetyltransferase (SAGA) complex is a highly conserved co-activator found across eukaryotes. It is composed of a number of modules which can vary between species, but all contain the core module. Hfi1 (known as TADA1 in Homo sapiens) is one of the proteins that forms the core module, and has been shown to play an important role in maintaining complex structural integrity in both brewer’s yeast and humans. In this study we successfully identified the gene encoding this protein in the important fungal pathogen, Cryptococcus neoformans, and named it HFI1. The hfi1Δ mutant is highly pleiotropic in vitro, influencing phenotypes, ranging from temperature sensitivity and melanin production to caffeine resistance and titan cell morphogenesis. In the absence of Hfi1, the transcription of several other SAGA genes is impacted, as is the acetylation and deubiquination of several histone residues. Importantly, loss of the gene significantly impacts virulence in a murine inhalation model of cryptococcosis. In summary, we have established that Hfi1 modulates multiple pathways that directly affect virulence and survival in C. neoformans, and provided deeper insight into the importance of the non-enzymatic components of the SAGA complex. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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20 pages, 3941 KiB  
Article
Mitogenome Variations in a Global Population of Aspergillus fumigatus
by Veronica Thorn and Jianping Xu
J. Fungi 2023, 9(10), 995; https://doi.org/10.3390/jof9100995 - 08 Oct 2023
Viewed by 1176
Abstract
Aspergillus fumigatus is a ubiquitous, critical priority human fungal pathogen. Despite its clinical importance, there is limited knowledge regarding the variations of the genome within mitochondria, the powerhouse organelle within eukaryotic cells. In this study, we leveraged publicly available, raw, whole genome sequence [...] Read more.
Aspergillus fumigatus is a ubiquitous, critical priority human fungal pathogen. Despite its clinical importance, there is limited knowledge regarding the variations of the genome within mitochondria, the powerhouse organelle within eukaryotic cells. In this study, we leveraged publicly available, raw, whole genome sequence data isolates from 1939 to investigate the variations in the mitochondrial genomes of A. fumigatus. These isolates were isolated from 22 countries on six continents, as well as from outer space and from within the International Space Station. In total, our analysis revealed 39 mitochondrial single nucleotide polymorphisms (mtSNPs) within this global sample, and, together, these 39 mtSNPs grouped the 1939 isolates into 79 mitochondrial multilocus genotypes (MLGs). Among the 79 MLGs, 39 were each distributed in at least two countries and 30 were each shared by at least two continents. The two most frequent MLGs were also broadly distributed: MLG11 represented 420 isolates from 11 countries and four continents and while MLG79 represented 418 isolates from 18 countries and five continents, consistent with long-distance dispersals of mitogenomes. Our population genetic analyses of the mtSNPs revealed limited differentiation among continental populations, but highly variable genetic differences among national populations, largely due to localized clonal expansions of different MLGs. Phylogenetic analysis and Discriminant Analysis of Principal Components of mtSNPs suggested the presence of at least three mitogenome clusters. Linkage disequilibrium, Index of Association, and phylogenetic incompatibility analyses collectively suggested evidence for mitogenome recombination in natural populations of A. fumigatus. In addition, sequence read depth analyses revealed an average ratio of ~20 mitogenomes per nuclear genome in this global population, but the ratios varied among strains within and between certain geographic populations. Together, our results suggest evidence for organelle dynamics, genetic differentiation, recombination, and both widespread and localized clonal expansion of the mitogenomes in the global A. fumigatus population. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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22 pages, 1567 KiB  
Article
Global Analyses of Multi-Locus Sequence Typing Data Reveal Geographic Differentiation, Hybridization, and Recombination in the Cryptococcus gattii Species Complex
by Megan Hitchcock and Jianping Xu
J. Fungi 2023, 9(2), 276; https://doi.org/10.3390/jof9020276 - 20 Feb 2023
Cited by 4 | Viewed by 2165
Abstract
Cryptococcus gattii species complex (CGSC) is a basidiomycete haploid yeast and globally distributed mammalian pathogen. CGSC is comprised of six distinct lineages (VGI, VGII, VGIII, VGIV, VGV, and VGVI); however, the geographical distribution and population structure of these lineages is incompletely described. In [...] Read more.
Cryptococcus gattii species complex (CGSC) is a basidiomycete haploid yeast and globally distributed mammalian pathogen. CGSC is comprised of six distinct lineages (VGI, VGII, VGIII, VGIV, VGV, and VGVI); however, the geographical distribution and population structure of these lineages is incompletely described. In this study, we analyze published multi-locus sequence data at seven loci for 566 previously recorded sequence types (STs) encompassing four distinct lineages (VGI, VGII, VGIII, and VGIV) within the CGSC. We investigate indicators of both clonal dispersal and recombination. Population genetic analyses of the 375 STs representing 1202 isolates with geographic information and 188 STs representing 788 isolates with ecological source data suggested historically differentiated geographic populations with infrequent long-distance gene flow. Phylogenetic analyses of sequences at the individual locus and of the concatenated sequences at all seven loci among all 566 STs revealed distinct clusters largely congruent with four major distinct lineages. However, 23 of the 566 STs (4%) each contained alleles at the seven loci belonging to two or more lineages, consistent with their hybrid origins among lineages. Within each of the four major lineages, phylogenetic incompatibility analyses revealed evidence for recombination. However, linkage disequilibrium analyses rejected the hypothesis of random recombination across all samples. Together, our results suggest evidence for historical geographical differentiation, sexual recombination, hybridization, and both long-distance and localized clonal expansion in the global CGSC population. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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13 pages, 954 KiB  
Article
Cryptococcus neoformans Causing Meningoencephalitis in Adults and a Child from Lima, Peru: Genotypic Diversity and Antifungal Susceptibility
by Carolina Firacative, Natalia Zuluaga-Puerto and José Guevara
J. Fungi 2022, 8(12), 1306; https://doi.org/10.3390/jof8121306 - 16 Dec 2022
Viewed by 1628
Abstract
Cryptococcosis, caused predominantly by Cryptococcus neoformans, is a potentially fatal, opportunistic infection that commonly affects the central nervous system of immunocompromised patients. Globally, this mycosis is responsible for almost 20% of AIDS-related deaths, and in countries like Peru, its incidence remains high, [...] Read more.
Cryptococcosis, caused predominantly by Cryptococcus neoformans, is a potentially fatal, opportunistic infection that commonly affects the central nervous system of immunocompromised patients. Globally, this mycosis is responsible for almost 20% of AIDS-related deaths, and in countries like Peru, its incidence remains high, mostly due to the annual increase in new cases of HIV infection. This study aimed to establish the genotypic diversity and antifungal susceptibility of C. neoformans isolates causing meningoencephalitis in 25 adults and a 9-year-old girl with HIV and other risk factors from Lima, Peru. To identify the genotype of the isolates, multilocus sequence typing was applied, and to establish the susceptibility of the isolates to six antifungals, a YeastOne® broth microdilution was used. From the isolates, 19 were identified as molecular type VNI, and seven as VNII, grouped in eight and three sequence types, respectively, which shows that the studied population was highly diverse. Most isolates were susceptible to all antifungals tested. However, VNI isolates were less susceptible to fluconazole, itraconazole and voriconazole than VNII isolates (p < 0.05). This study contributes data on the molecular epidemiology and the antifungal susceptibility profile of the most common etiological agent of cryptococcosis, highlighting a pediatric case, something which is rare among cryptococcal infection. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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12 pages, 2354 KiB  
Article
Genotypic Diversity of Candida parapsilosis Complex in Invasive Candidiasis at a Pediatric Tertiary Hospital: A 5-Year Retrospective Study
by Luiza S. Rodrigues, Adriele C. Siqueira, Regiane N. Spalanzani, Thaís M. Vasconcelos, Bianca Sestren, Saloe P. Bispo, Renata B. V. Abreu, Letícia Kraft, Marinei C. Ricieri, Fábio A. Motta and Libera M. Dalla-Costa
J. Fungi 2022, 8(12), 1280; https://doi.org/10.3390/jof8121280 - 06 Dec 2022
Cited by 2 | Viewed by 1862
Abstract
Invasive candidiasis (IC) contributes to the morbidity and mortality of hospitalized patients and represents a significant burden to the healthcare system. Previous Brazilian studies have reported the presence of endemic Candida parapsilosis sensu stricto genotypes causing candidemia and clonal transmission involving fluconazole-resistant isolates. [...] Read more.
Invasive candidiasis (IC) contributes to the morbidity and mortality of hospitalized patients and represents a significant burden to the healthcare system. Previous Brazilian studies have reported the presence of endemic Candida parapsilosis sensu stricto genotypes causing candidemia and clonal transmission involving fluconazole-resistant isolates. We performed a 5-year retrospective analysis of IC cases in a Brazilian tertiary pediatric hospital and conducted a molecular investigation of C. parapsilosis sensu stricto. Non-duplicate C. parapsilosis sensu stricto genotyping was performed by microsatellite analysis. Antifungal susceptibility and biofilm formation were also evaluated. A total of 123 IC episodes were identified, with an IC incidence of 1.24 cases per 1000 hospital admissions and an overall mortality of 34%. The main species were the C. parapsilosis complex (35.8%), Candida albicans (29.2%), and Candida tropicalis (21.9%). All C. parapsilosis sensu stricto were recovered from blood cultures, and 97.5% were biofilm producers. Microsatellite typing identified high genotypic diversity among the isolates. We observed that all isolates were sensitive to amphotericin B, and although one isolate was non-sensitive to fluconazole, only a silent mutation on ERG11 gene was identified. No clear evidence of clonal outbreak or emergence of fluconazole-resistant isolates was found, suggesting that multiple sources may be involved in the epidemiology of IC in children. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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31 pages, 8001 KiB  
Article
Melanization of Candida auris Is Associated with Alteration of Extracellular pH
by Daniel F. Q. Smith, Nathan J. Mudrak, Daniel Zamith-Miranda, Leandro Honorato, Leonardo Nimrichter, Christine Chrissian, Barbara Smith, Gary Gerfen, Ruth E. Stark, Joshua D. Nosanchuk and Arturo Casadevall
J. Fungi 2022, 8(10), 1068; https://doi.org/10.3390/jof8101068 - 11 Oct 2022
Cited by 4 | Viewed by 4931
Abstract
Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove biofilms. [...] Read more.
Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove biofilms. Due to the relatively recent, resilient, and resistant nature of C. auris, we investigated whether it produces the common fungal virulence factor melanin. Melanin is a black-brown pigment typically produced following enzymatic oxidation of aromatic precursors, which promotes fungal virulence through oxidative stress resistance, mammalian immune response evasion, and antifungal peptide and pharmaceutical inactivation. We found that certain strains of C. auris oxidized L-DOPA and catecholamines into melanin. Melanization occurred extracellularly in a process mediated by alkalinization of the extracellular environment, resulting in granule-like structures that adhere to the fungus’ external surface. C. auris had relatively high cell surface hydrophobicity, but there was no correlation between hydrophobicity and melanization. Melanin protected the fungus from oxidative damage, but we did not observe a protective role during infection of macrophages or Galleria mellonella larvae. In summary, C. auris alkalinizes the extracellular medium, which promotes the non-enzymatic oxidation of L-DOPA to melanin that attaches to its surface, thus illustrating a novel mechanism for fungal melanization. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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Review

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12 pages, 1492 KiB  
Review
Specifically Targeting Metacaspases of Candida: A New Therapeutic Opportunity
by Anne-Lise Bienvenu, Lionel Ballut and Stephane Picot
J. Fungi 2024, 10(2), 90; https://doi.org/10.3390/jof10020090 - 23 Jan 2024
Viewed by 1069
Abstract
The World Health Organization (WHO) recently published a list of fungal priority pathogens, including Candida albicans and C. auris. The increased level of resistance of Candida is raising concern, considering the availability of only four classes of medicine. The WHO is seeking [...] Read more.
The World Health Organization (WHO) recently published a list of fungal priority pathogens, including Candida albicans and C. auris. The increased level of resistance of Candida is raising concern, considering the availability of only four classes of medicine. The WHO is seeking novel agent classes with different targets and mechanisms of action. Targeting Candida metacaspases to control intrinsic cell death could provide new therapeutic opportunities for invasive candidiasis. In this review, we provide the available evidence for Candida cell death, describe Candida metacaspases, and discuss the potential of Candida metacaspases to offer a new specific target. Targeting Candida cell death has good scientific rationale given that the fungicidal activity of many marketed antifungals is mediated, among others, by cell death triggering. But none of the available antifungals are specifically activating Candida metacaspases, making this target a new therapeutic opportunity for non-susceptible isolates. It is expected that antifungals based on the activation of fungi metacaspases will have a broad spectrum of action, as metacaspases have been described in many fungi, including filamentous fungi. Considering this original mechanism of action, it could be of great interest to combine these new antifungal candidates with existing antifungals. This approach would help to avoid the development of antifungal resistance, which is especially increasing in Candida. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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17 pages, 1675 KiB  
Review
Innate Pulmonary Phagocytes and Their Interactions with Pathogenic Cryptococcus Species
by Brittney N. Conn and Karen L. Wozniak
J. Fungi 2023, 9(6), 617; https://doi.org/10.3390/jof9060617 - 27 May 2023
Cited by 2 | Viewed by 1510
Abstract
Cryptococcus neoformans is an opportunistic fungal pathogen that causes over 180,000 annual deaths in HIV/AIDS patients. Innate phagocytes in the lungs, such as dendritic cells (DCs) and macrophages, are the first cells to interact with the pathogen. Neutrophils, another innate phagocyte, are recruited [...] Read more.
Cryptococcus neoformans is an opportunistic fungal pathogen that causes over 180,000 annual deaths in HIV/AIDS patients. Innate phagocytes in the lungs, such as dendritic cells (DCs) and macrophages, are the first cells to interact with the pathogen. Neutrophils, another innate phagocyte, are recruited to the lungs during cryptococcal infection. These innate cells are involved in early detection of C. neoformans, as well as the removal and clearance of cryptococcal infections. However, C. neoformans has developed ways to interfere with these processes, allowing for the evasion of the host’s innate immune system. Additionally, the innate immune cells have the ability to aid in cryptococcal pathogenesis. This review discusses recent literature on the interactions of innate pulmonary phagocytes with C. neoformans. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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16 pages, 1140 KiB  
Review
Sterylglucosides in Fungi
by Nivea Pereira de Sa and Maurizio Del Poeta
J. Fungi 2022, 8(11), 1130; https://doi.org/10.3390/jof8111130 - 26 Oct 2022
Viewed by 2041
Abstract
Sterylglucosides (SGs) are sterol conjugates widely distributed in nature. Although their universal presence in all living organisms suggests the importance of this kind of glycolipids, they are yet poorly understood. The glycosylation of sterols confers a more hydrophilic character, modifying biophysical properties of [...] Read more.
Sterylglucosides (SGs) are sterol conjugates widely distributed in nature. Although their universal presence in all living organisms suggests the importance of this kind of glycolipids, they are yet poorly understood. The glycosylation of sterols confers a more hydrophilic character, modifying biophysical properties of cell membranes and altering immunogenicity of the cells. In fungi, SGs regulate different cell pathways to help overcome oxygen and pH challenges, as well as help to accomplish cell recycling and other membrane functions. At the same time, the level of these lipids is highly controlled, especially in wild-type fungi. In addition, modulating SGs metabolism is becoming a novel tool for vaccine and antifungal development. In the present review, we bring together multiple observations to emphasize the underestimated importance of SGs for fungal cell functions. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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17 pages, 1746 KiB  
Review
Alternative Transcription Start Site Usage and Functional Implications in Pathogenic Fungi
by Thi Tuong Vi Dang, Jessie Colin and Guilhem Janbon
J. Fungi 2022, 8(10), 1044; https://doi.org/10.3390/jof8101044 - 03 Oct 2022
Cited by 1 | Viewed by 3052
Abstract
Pathogenic fungi require delicate gene regulation mechanisms to adapt to diverse living environments and escape host immune systems. Recent advances in sequencing technology have exposed the complexity of the fungal genome, thus allowing the gradual disentanglement of multiple layers of gene expression control. [...] Read more.
Pathogenic fungi require delicate gene regulation mechanisms to adapt to diverse living environments and escape host immune systems. Recent advances in sequencing technology have exposed the complexity of the fungal genome, thus allowing the gradual disentanglement of multiple layers of gene expression control. Alternative transcription start site (aTSS) usage, previously reported to be prominent in mammals and to play important roles in physiopathology, is also present in fungi to fine-tune gene expression. Depending on the alteration in their sequences, RNA isoforms arising from aTSSs acquire different characteristics that significantly alter their stability and translational capacity as well as the properties and biologic functions of the resulting proteins. Disrupted control of aTSS usage has been reported to severely impair growth, virulence, and the infectious capacity of pathogenic fungi. Here, we discuss principle concepts, mechanisms, and the functional implication of aTSS usage in fungi. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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8 pages, 715 KiB  
Opinion
A Quick reCAP: Discovering Cryptococcus neoformans Capsule Mutants
by Daphne Boodwa-Ko and Tamara L. Doering
J. Fungi 2024, 10(2), 114; https://doi.org/10.3390/jof10020114 - 30 Jan 2024
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Abstract
Cryptococcus neoformans is an opportunistic fungal pathogen that can cause severe meningoencephalitis in immunocompromised hosts and is a leading cause of death in HIV/AIDS patients. This pathogenic yeast is surrounded by a polysaccharide capsule that is critical for virulence and plays important roles [...] Read more.
Cryptococcus neoformans is an opportunistic fungal pathogen that can cause severe meningoencephalitis in immunocompromised hosts and is a leading cause of death in HIV/AIDS patients. This pathogenic yeast is surrounded by a polysaccharide capsule that is critical for virulence and plays important roles in host-pathogen interactions. Understanding capsule biosynthesis is therefore key to defining the biology of C. neoformans and potentially discovering novel therapeutic targets. By exploiting methods to identify mutants deficient in capsule, June Kwon-Chung and other investigators have discovered numerous genes involved in capsule biosynthesis and regulation. Successful approaches have incorporated combinations of techniques including mutagenesis and systematic gene deletion; complementation and genetic screens; morphological examination, physical separation, and antibody binding; and computational modeling based on gene expression analysis. In this review, we discuss these methods and how they have been used to identify capsule mutants. Full article
(This article belongs to the Special Issue Fifty Years of Fungi: A Special Issue Honoring the Contributions of Dr. June Kwon-Chung to the Field of Medical Mycology)
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