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Pathogenesis in Human Fungal Pathogens
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Pathogenesis in Human Fungal Pathogens

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 (31 December 2023) | Viewed by 12760

Special Issue Editors

Prof. Dr. Tongbao Liu

E-Mail Website
Guest Editor
Medical Research Institute, Southwest University, Chongqing, China
Interests: human fungal pathogens; Cryptococcus neoformans; fungal pathogenesis; fungal virulence; pathogen–host interaction; ubiquitin–proteasome system; autophagy
Prof. Dr. Chen Ding

E-Mail Website
Guest Editor
College of Life and Health Sciences, Northeastern University, Shenyang, China
Interests: human fungal pathogens; Cryptococcus neoformans; metal homeostasis; drug resistance; fungal pathogenicity evolution

Special Issue Information

Dear Colleagues,

Fungal pathogens infect about 1.2 billion people worldwide and cause the death of an estimated 1.5 to 2 million people each year, surpassing those killed by either tuberculosis or malaria. However, the current antifungal drug treatments for invasive fungal infections are limited to polyenes, azoles, and echinocandins. Unfortunately, the widespread use of antifungal drugs has accelerated the rapid emergence of resistance to all three classes of antifungal drugs, which also exacerbates the public health burden. However, the current dilemma of fungal treatment is that our general lack of research capabilities for fungal pathogens hinders our understanding of fungal diseases and the development of faster diagnostic methods and new therapies. Therefore, in-depth research leading to a greater understanding of fungal pathogenesis can help towards the proposal of new, targeted strategies to overcome fungal infections to improve our ability to fight fungal pathogens and reduce and possibly even reverse the effects of drug-resistant evolution. To increase our awareness of this topic, we are launching this Special Issue to emphasize the progress made in relation to fungal pathogenesis, which is important for fungal pathogen research.

Prof. Dr. Tongbao Liu
Prof. Dr. Chen Ding 
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Keywords

  • human fungal pathogens
  • fungal pathogenesis
  • pathogen-host interaction
  • drug resistance

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Published Papers (5 papers)

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Research

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19 pages, 4031 KiB  
Article
Multi-Locus Microsatellite Typing of Colonising and Invasive Aspergillus fumigatus Isolates from Patients Post Lung Transplantation and with Chronic Lung Disease
by Joshua D. Birnie, Tanveer Ahmed, Sarah E. Kidd, Glen P. Westall, Gregory I. Snell, Anton Y. Peleg and Catherine Orla Morrissey
J. Fungi 2024, 10(2), 95; https://doi.org/10.3390/jof10020095 - 24 Jan 2024
Cited by 1 | Viewed by 1534
Abstract
Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, [...] Read more.
Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006–31 March 2009 and 1 November 2015–30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson’s diversity index of 0.9819–0.9942) with no dominant strain detected. No specific genotype–phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01–279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains. Full article
(This article belongs to the Special Issue Pathogenesis in Human Fungal Pathogens)
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20 pages, 3624 KiB  
Article
Transcriptional Reprogramming of Candida tropicalis in Response to Isoespintanol Treatment
by Orfa Inés Contreras-Martínez, Alberto Angulo-Ortíz, Gilmar Santafé-Patiño, Katia Aviña-Padilla, María Camila Velasco-Pareja and María Fernanda Yasnot
J. Fungi 2023, 9(12), 1199; https://doi.org/10.3390/jof9121199 - 15 Dec 2023
Cited by 2 | Viewed by 2591
Abstract
Candida tropicalis, an opportunistic pathogen, ranks among the primary culprits of invasive candidiasis, a condition notorious for its resistance to conventional antifungal drugs. The urgency to combat these drug-resistant infections has spurred the quest for novel therapeutic compounds, with a particular focus [...] Read more.
Candida tropicalis, an opportunistic pathogen, ranks among the primary culprits of invasive candidiasis, a condition notorious for its resistance to conventional antifungal drugs. The urgency to combat these drug-resistant infections has spurred the quest for novel therapeutic compounds, with a particular focus on those of natural origin. In this study, we set out to evaluate the impact of isoespintanol (ISO), a monoterpene derived from Oxandra xylopioides, on the transcriptome of C. tropicalis. Leveraging transcriptomics, our research aimed to unravel the intricate transcriptional changes induced by ISO within this pathogen. Our differential gene expression analysis unveiled 186 differentially expressed genes (DEGs) in response to ISO, with a striking 85% of these genes experiencing upregulation. These findings shed light on the multifaceted nature of ISO’s influence on C. tropicalis, spanning a spectrum of physiological, structural, and metabolic adaptations. The upregulated DEGs predominantly pertained to crucial processes, including ergosterol biosynthesis, protein folding, response to DNA damage, cell wall integrity, mitochondrial activity modulation, and cellular responses to organic compounds. Simultaneously, 27 genes were observed to be repressed, affecting functions such as cytoplasmic translation, DNA damage checkpoints, membrane proteins, and metabolic pathways like trans-methylation, trans-sulfuration, and trans-propylamine. These results underscore the complexity of ISO’s antifungal mechanism, suggesting that it targets multiple vital pathways within C. tropicalis. Such complexity potentially reduces the likelihood of the pathogen developing rapid resistance to ISO, making it an attractive candidate for further exploration as a therapeutic agent. In conclusion, our study provides a comprehensive overview of the transcriptional responses of C. tropicalis to ISO exposure. The identified molecular targets and pathways offer promising avenues for future research and the development of innovative antifungal therapies to combat infections caused by this pathogenic yeast. Full article
(This article belongs to the Special Issue Pathogenesis in Human Fungal Pathogens)
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15 pages, 3742 KiB  
Article
Antifungal Effect of Vitamin D3 against Cryptococcus neoformans Coincides with Reduced Biofilm Formation, Compromised Cell Wall Integrity, and Increased Generation of Reactive Oxygen Species
by Jian Huang, Junwen Lei, Anni Ge, Wei Xiao, Caiyan Xin, Zhangyong Song and Jinping Zhang
J. Fungi 2023, 9(7), 772; https://doi.org/10.3390/jof9070772 - 21 Jul 2023
Cited by 4 | Viewed by 2303
Abstract
Cryptococcus neoformans is an invasive fungus that causes both acute and chronic infections, especially in immunocompromised patients. Owing to the increase in the prevalence of drug-resistant pathogenic fungi and the limitations of current treatment strategies, drug repositioning has become a feasible strategy to [...] Read more.
Cryptococcus neoformans is an invasive fungus that causes both acute and chronic infections, especially in immunocompromised patients. Owing to the increase in the prevalence of drug-resistant pathogenic fungi and the limitations of current treatment strategies, drug repositioning has become a feasible strategy to accelerate the development of new drugs. In this study, the minimum inhibitory concentration of vitamin D3 (VD3) against C. neoformans was found to be 0.4 mg/mL by broth microdilution assay. The antifungal activities of VD3 were further verified by solid dilution assays and “time-kill” curves. The results showed that VD3 reduced fungal cell adhesion and hydrophobicity and inhibited biofilm formation at various developmental stages, as confirmed by crystal violet staining and the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Fluorescence staining of cellular components and a stress susceptibility assay indicated that VD3 compromised cell integrity. Reverse transcription quantitative PCR demonstrated that VD3 treatment upregulated the expression of fungal genes related to cell wall synthesis (i.e., CDA3, CHS3, FKS1, and AGS1). Moreover, VD3 enhanced cell membrane permeability and caused the accumulation of intracellular reactive oxygen species. Finally, VD3 significantly reduced the tissue fungal burden and prolonged the survival of Galleria mellonella larvae infected with C. neoformans. These results showed that VD3 could exert significant antifungal activities both in vitro and in vivo, demonstrating its potential application in the treatment of cryptococcal infections. Full article
(This article belongs to the Special Issue Pathogenesis in Human Fungal Pathogens)
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Review

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24 pages, 3172 KiB  
Review
Mechanisms and Virulence Factors of Cryptococcus neoformans Dissemination to the Central Nervous System
by Ammar Mutahar Al-Huthaifi, Bakeel A. Radman, Abdullah Ali Al-Alawi, Fawad Mahmood and Tong-Bao Liu
J. Fungi 2024, 10(8), 586; https://doi.org/10.3390/jof10080586 - 17 Aug 2024
Viewed by 1796
Abstract
Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to [...] Read more.
Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the “Trojan horse” mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans. Full article
(This article belongs to the Special Issue Pathogenesis in Human Fungal Pathogens)
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29 pages, 3967 KiB  
Review
Alternative Non-Mammalian Animal and Cellular Methods for the Study of Host–Fungal Interactions
by Ana Marisa Fusco-Almeida, Samanta de Matos Silva, Kelvin Sousa dos Santos, Marcos William de Lima Gualque, Carolina Orlando Vaso, Angélica Romão Carvalho, Kaila Petrolina Medina-Alarcón, Ana Carolina Moreira da Silva Pires, Jenyffie Araújo Belizario, Lígia de Souza Fernandes, Andrei Moroz, Luis R. Martinez, Orville Hernandez Ruiz, Ángel González and Maria José Soares Mendes-Giannini
J. Fungi 2023, 9(9), 943; https://doi.org/10.3390/jof9090943 - 19 Sep 2023
Cited by 2 | Viewed by 3671
Abstract
In the study of fungal pathogenesis, alternative methods have gained prominence due to recent global legislation restricting the use of mammalian animals in research. The principle of the 3 Rs (replacement, reduction, and refinement) is integrated into regulations and guidelines governing animal experimentation [...] Read more.
In the study of fungal pathogenesis, alternative methods have gained prominence due to recent global legislation restricting the use of mammalian animals in research. The principle of the 3 Rs (replacement, reduction, and refinement) is integrated into regulations and guidelines governing animal experimentation in nearly all countries. This principle advocates substituting vertebrate animals with other invertebrate organisms, embryos, microorganisms, or cell cultures. This review addresses host–fungus interactions by employing three-dimensional (3D) cultures, which offer more faithful replication of the in vivo environment, and by utilizing alternative animal models to replace traditional mammals. Among these alternative models, species like Caenorhabditis elegans and Danio rerio share approximately 75% of their genes with humans. Furthermore, models such as Galleria mellonella and Tenebrio molitor demonstrate similarities in their innate immune systems as well as anatomical and physiological barriers, resembling those found in mammalian organisms. Full article
(This article belongs to the Special Issue Pathogenesis in Human Fungal Pathogens)
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