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Pathogenicity and Molecular Biology of Human Pathogenic Fungi
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Pathogenicity and Molecular Biology of Human Pathogenic Fungi

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Genomics, Genetics and Molecular Biology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 11563

Special Issue Editors

Prof. Dr. Maristela Pereira

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Guest Editor
Laboratory of Molecular Biology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil
Interests: antimicrobials; drug; genomics; transcriptomics; proteomics; bioinformatics; microbiology
Prof. Dr. Celia Maria De Almeida Soares

E-Mail Website
Guest Editor
Laboratory of Molecular Biology, Institute of Biological Sciences, Universidade Federal de Goiás, Goiânia, Brazil
Interests: molecular biology; proteomics; genomics; transcriptomics; biochemistry; microbiology
Prof. Dr. Marilene Henning Vainstein

E-Mail Website
Guest Editor
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
Interests: fungal pathogens; microbiology; biotechnology; environmental microbiology

Special Issue Information

Dear Colleagues,

This Special Issue will be dedicated to human pathogenic fungi. In general, it will cover aspects related to pathogenicity and involving molecular biology. Knowledge of host–pathogen relationships is of emerging interest, and aspects of this interaction will be included. The discovery of compounds and peptides, both natural and synthetic or semi-synthetic, that may interfere in this relationship is receiving increased attention, and some of these compounds/molecules have become potential drugs for the treatment of fungal diseases. Aspects involving the use of methodologies in molecular biology in general, including omics methodologies, are also of interest. Finally, any new developments occurring in this field will also be included.

Prof. Dr. Maristela Pereira
Prof. Dr. Celia Maria De Almeida Soares
Prof. Dr. Marilene Henning Vainstein
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

  • pathogenicity
  • human pathogenic fungi
  • host–pathogen relationship
  • molecular biology
  • drug

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Published Papers (5 papers)

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Research

19 pages, 3850 KiB  
Article
Polypeptides Targeting Paracoccidioides brasiliensis Drk1
by Caroline Maria Marcos, Haroldo Cesar de Oliveira, Patricia Akemi Assato, Lariane Teodoro de Oliveira, Nathália Fregonezi, Kelvin Sousa dos Santos, Caroline Barcelos Costa-Orlandi, Ana Marisa Fusco-Almeida and Maria José Soares Mendes-Giannini
J. Fungi 2023, 9(10), 980; https://doi.org/10.3390/jof9100980 - 29 Sep 2023
Cited by 1 | Viewed by 1224
Abstract
Considering the toxicity of conventional therapeutic approaches and the importance of precise mechanistic targets, it is important to explore signaling pathways implicated in fungal pathobiology. Moreover, treatment of paracoccidioidomycosis, a systemic mycosis caused by a dimorphic fungus, requires prolonged therapeutic regimens. Among the [...] Read more.
Considering the toxicity of conventional therapeutic approaches and the importance of precise mechanistic targets, it is important to explore signaling pathways implicated in fungal pathobiology. Moreover, treatment of paracoccidioidomycosis, a systemic mycosis caused by a dimorphic fungus, requires prolonged therapeutic regimens. Among the numerous factors underpinning the establishment of Paracoccidioides spp. infection, the capacity to transition from the mycelial to the yeast form is of pivotal importance. The Drk1 protein of Paracoccidioides brasiliensis likely plays a decisive role in this morphological shift and subsequent virulence. We identified peptides with affinity for the PbDrk1 protein using the phage-display method and assessed the effects of these peptides on P. brasiliensis. The peptides were found to inhibit the phase transition of P. brasiliensis. Furthermore, a substantial proportion of these peptides prevented adhesion to pneumocytes. Although these peptides may not possess inherent antifungal properties, they can augment the effects of certain antifungal agents. Notably, the cell wall architecture of P. brasiliensis appears to be modulated by peptide intervention, resulting in a reduced abundance of glycosylated proteins and lipids. These peptides were also evaluated for their efficacy in a Galleria mellonella model and shown to contribute to enhanced larval survival rates. The role of PbDrk1, which is notably absent in mammals, should be further investigated to improve the understanding of its functional role in P. brasiliensis, which may be helpful for designing novel therapeutic modalities. Full article
(This article belongs to the Special Issue Pathogenicity and Molecular Biology of Human Pathogenic Fungi)
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10 pages, 270 KiB  
Article
Comprehensive Taxonomical Analysis of Trichophyton mentagrophytes/interdigitale Complex of Human and Animal Origin from India
by Shivaprakash M. Rudramurthy, Dipika Shaw, Shamanth Adekhandi Shankarnarayan, Abhishek and Sunil Dogra
J. Fungi 2023, 9(5), 577; https://doi.org/10.3390/jof9050577 - 16 May 2023
Cited by 5 | Viewed by 2559
Abstract
Taxonomic delineation of etiologic agents responsible for recalcitrant dermatophytosis causing an epidemic in India is still debated. The organism responsible for this epidemic is designated as T. indotineae, a clonal offshoot of T. mentagrophytes. To evaluate the real identity of the [...] Read more.
Taxonomic delineation of etiologic agents responsible for recalcitrant dermatophytosis causing an epidemic in India is still debated. The organism responsible for this epidemic is designated as T. indotineae, a clonal offshoot of T. mentagrophytes. To evaluate the real identity of the agent causing this epidemic, we performed a multigene sequence analysis of Trichophyton species isolated from human and animal origin. We included Trichophyton species isolated from 213 human and six animal hosts. Internal transcribed spacer (ITS) (n = 219), translational elongation factors (TEF 1-α) (n = 40), ß-tubulin (BT) (n = 40), large ribosomal subunit (LSU) (n = 34), calmodulin (CAL) (n = 29), high mobility group (HMG) transcription factor gene (n = 17) and α-box gene (n = 17) were sequenced. Our sequences were compared with Trichophyton mentagrophytes species complex sequences in the NCBI database. Except for one isolate (ITS genotype III) from animal origin, all the tested genes grouped our isolates and belonged to the “Indian ITS genotype”, currently labeled as T. indotineae. ITS and TEF 1-α were more congruent compared to other genes. In this study, for the first time, we isolated the T mentagrophytes ITS Type VIII from animal origin, suggesting the role of zoonotic transmission in the ongoing epidemic. Isolation of T. mentagrophytes type III only from animal indicates its niche among animals. Outdated/inaccurate naming for these dermatophytes in the public database has created confusion in using appropriate species designation. Full article
(This article belongs to the Special Issue Pathogenicity and Molecular Biology of Human Pathogenic Fungi)
19 pages, 4280 KiB  
Article
Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism
by Rafael de Souza Silva, Wilson Dias Segura, Reinaldo Souza Oliveira, Patricia Xander and Wagner Luiz Batista
J. Fungi 2023, 9(3), 375; https://doi.org/10.3390/jof9030375 - 19 Mar 2023
Cited by 1 | Viewed by 2239
Abstract
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. The infection begins after inhalation of the fungal propagules and their thermo-dimorphic shift to yeast form. Proteases play an important role in the [...] Read more.
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. The infection begins after inhalation of the fungal propagules and their thermo-dimorphic shift to yeast form. Proteases play an important role in the host invasion process and immune modulation in many pathogenic microorganisms. Aspartyl proteases are virulence factors in many human fungal pathogens that play an important role in the host invasion process morphogenesis, cellular function, immunity, and nutrition. In the present study, we characterized the modulation of acid proteases from Paracoccidioides brasiliensis. We detected four aspartyl proteases in P. brasiliensis with high homology to aspartic protease from Saccharomyces cerevisiae Pep4. Furthermore, we demonstrated that Pepstatin A can inhibit dimorphic switching (mycelium→yeast) in P. brasiliensis. In addition, these genes were modulated during thermo-dimorphism (M→Y transition) in the presence or absence of carbon and nitrogen sources and during growth at pH 4 during 24 and 48 h. We also observed that P. brasiliensis increase the secretion of aspartic proteases when cultivated at pH 4, and these acid proteases cleave BSA, collagen, and hemoglobin. These data suggest that aspartyl proteases are modulated by environmental conditions and during fungal thermo-dimorphism. Thus, this work brings new possibilities for studying the role of aspartyl proteases in the host–pathogen relationship and P. brasiliensis biology. Full article
(This article belongs to the Special Issue Pathogenicity and Molecular Biology of Human Pathogenic Fungi)
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17 pages, 11070 KiB  
Article
Anti-Biofilm Activity of Phenyllactic Acid against Clinical Isolates of Fluconazole-Resistant Candida albicans
by Angela Maione, Marianna Imparato, Annalisa Buonanno, Federica Carraturo, Antonetta Schettino, Maria Teresa Schettino, Marilena Galdiero, Elisabetta de Alteriis, Marco Guida and Emilia Galdiero
J. Fungi 2023, 9(3), 355; https://doi.org/10.3390/jof9030355 - 15 Mar 2023
Cited by 10 | Viewed by 2521
Abstract
Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region, and is responsible for 85% to 90% of vulvovaginal candidiasis (VVC) cases. The development of drug resistance in C. albicans [...] Read more.
Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region, and is responsible for 85% to 90% of vulvovaginal candidiasis (VVC) cases. The development of drug resistance in C. albicans isolates after long-term therapy with fluconazole is an important complication to solve and new therapeutic strategies are required to target this organism and its pathogenicity. In the present study, phenyllactic acid (PLA) an important broad-spectrum antimicrobial compound was investigated for its antifungal and antivirulence activities against clinical isolates of C. albicans. Previously characterized strains of C. albicans isolates from women with VVC and C. albicans ATCC90028 were used to evaluate the antimicrobial and time dependent killing assay activity of PLA showing a MIC 7.5 mg mL−1 and a complete reduction of viable Candida cells detected by killing kinetics after 4 h of treatment with PLA. Additionally, PLA significantly reduced the biomass and the metabolic activity of C. albicans biofilms and impaired biofilm formation also with changes in ERG11, ALS3, and HWP1 genes expression as detected by qPCR. PLA eradicated pre-formed biofilms as showed also with confocal laser scanning microscopy (CLSM) observations. Furthermore, the compound prolonged the survival rate of Galleria mellonella infected by C. albicans isolates. These results indicate that PLA is a promising candidate as novel and safe antifungal agents for the treatment of vulvovaginal candidiasis. Full article
(This article belongs to the Special Issue Pathogenicity and Molecular Biology of Human Pathogenic Fungi)
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11 pages, 744 KiB  
Article
Short Tandem Repeat Genotyping and Antifungal Susceptibility Testing of Latin American Candida tropicalis Isolates
by Bram Spruijtenburg, Cynthea C. S. Z. Baqueiro, Arnaldo L. Colombo, Eelco F. J. Meijer, João N. de Almeida, Jr., Indira Berrio, Norma B. Fernández, Guilherme M. Chaves, Jacques F. Meis, Theun de Groot and on behalf of the Latin American Group for Investigating Candida Tropicalis Resistance
J. Fungi 2023, 9(2), 207; https://doi.org/10.3390/jof9020207 - 5 Feb 2023
Cited by 8 | Viewed by 2432
Abstract
Candida tropicalis is emerging as one of the most common Candida species causing opportunistic infections in Latin America. Outbreak events caused by C. tropicalis were reported, and antifungal resistant isolates are on the rise. In order to investigate population genomics and look into [...] Read more.
Candida tropicalis is emerging as one of the most common Candida species causing opportunistic infections in Latin America. Outbreak events caused by C. tropicalis were reported, and antifungal resistant isolates are on the rise. In order to investigate population genomics and look into antifungal resistance, we applied a short tandem repeat (STR) genotyping scheme and antifungal susceptibility testing (AFST) to 230 clinical and environmental C. tropicalis isolates from Latin American countries. STR genotyping identified 164 genotypes, including 11 clusters comprised of three to seven isolates, indicating outbreak events. AFST identified one isolate as anidulafungin-resistant and harboring a FKS1 S659P substitution. Moreover, we identified 24 clinical and environmental isolates with intermediate susceptibility or resistance to one or more azoles. ERG11 sequencing revealed each of these isolates harboring a Y132F and/or Y257H/N substitution. All of these isolates, except one, were clustered together in two groups of closely related STR genotypes, with each group harboring distinct ERG11 substitutions. The ancestral C. tropicalis strain of these isolates likely acquired the azole resistance-associated substitutions and subsequently spread across vast distances within Brazil. Altogether, this STR genotyping scheme for C. tropicalis proved to be useful for identifying unrecognized outbreak events and better understanding population genomics, including the spread of antifungal-resistant isolates. Full article
(This article belongs to the Special Issue Pathogenicity and Molecular Biology of Human Pathogenic Fungi)
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