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Microorganisms
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Paracoccidioidomycosis
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Paracoccidioidomycosis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 6975

Special Issue Editor

Dr. Rinaldo Pôncio Mendes

E-Mail Website
Guest Editor
Faculdade de Medicina de Botucatu, São Paulo State University (Unesp), Botucatu, SP, Brazil
Interests: medical mycology; fungal infection; clinical mycology; endemic mycosis; diagnostic microbiology

Special Issue Information

Dear Colleagues,

Paracoccidioidomycosis (PCM) is a systemic mycosis that is caused by thermally dimorphic fungi of the Paracoccidioides genus, which lives in the soil and infects rural workers in Latin America. PCM patients present antigen-specific immunosuppression that they are unable to recover after receiving appropriate treatment. The involvement of different organs has been reported, but the lungs, lymph nodes, skin, and mucous membranes of the air–digestive tract are predominantly affected. It is easy relatively easy to confirm a diagnosis of this condition because typical Paracoccidioides yeast forms can be identified by direct mycological examination in most clinical materials. However, it is difficult to isolate in culture because of its slow growth, causing delays and hindering its genotyping, the evaluation of its virulence and immunogenicity and, when indicated, the determination of its antifungal susceptibility. Few antifungal compounds are available for PCM treatment, with treatments requiring long amounts of time and high patient compliance in order to be effective. Nevertheless, in spite of an appropriate treatment, sequelae and relapse have been observed. Sequelae can be intense enough to endanger professional activity and, in this case, PCM is an occupational disease. Relapse has been observed in about 5% of cases because treatment does not eradicate all of the fungal cells, and part of them remain alive in the latent foci. These relapses are usually late, after the patient has been discharged from outpatient services. Thus, the criteria used to develop cures should be chosen carefully, and currently, a practical biomarker permitting the discontinuation of the antifungal compound discontinuation as well to predict cell-mediated immunity is under investigation. Unfortunately, the medical and social impact of PCM has seldom been evaluated.

PCM researchers are invited to contribute to this Special Issue, which aims different aspects of this type of mycosis. In addition, the Special Issue will focus on several issues that have not received much attention, such as central nervous system involvement and the medical and social impacts of PCM. Experimental studies answering questions that have emerged from clinical findings and that constitute translational research are eligible for inclusion. There are several aspects of PCM that should be evaluated in more depth, including the antifungal compounds that are routinely used in PCM therapy. Reaching a balance between the different aspects of the disease is of interest. The final design of this issue can be presented after researchers have been contacted.

Dr. Rinaldo Pôncio Mendes
Guest Editor

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. Microorganisms 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 2700 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 (5 papers)

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Research

16 pages, 2310 KiB  
Article
Standardization of Semi-Quantitative Dot Blotting Assay—Application in the Diagnosis, Follow-Up, and Relapse of Paracoccidioidomycosis
by Beatriz Aparecida Soares Pereira, Ricardo de Souza Cavalcante, Vera Lucia Pereira-Chioccola, Marcia de Souza Carvalho Melhem, Lídia Raquel de Carvalho and Rinaldo Poncio Mendes
Microorganisms 2024, 12(2), 351; https://doi.org/10.3390/microorganisms12020351 - 8 Feb 2024
Viewed by 609
Abstract
Introduction: This study standardized a semi-quantitative dot blotting assay (DB) and a quantitative real-time polymerase chain reaction (qPCR) to detect specific antibodies for Paracoccidioides brasiliensis and its DNA in PCM patients. Methodology: We evaluated 42 confirmed PCM patients upon admission using a serological [...] Read more.
Introduction: This study standardized a semi-quantitative dot blotting assay (DB) and a quantitative real-time polymerase chain reaction (qPCR) to detect specific antibodies for Paracoccidioides brasiliensis and its DNA in PCM patients. Methodology: We evaluated 42 confirmed PCM patients upon admission using a serological double agar gel immunodiffusion test (DID), DB, and molecular tests (qPCR in total blood). The control groups included 42 healthy individuals and 37 patients with other infectious diseases. The serological progress during treatment was evaluated in eight patients, and there was a relapse diagnosis in ten patients using the Pb B.339 strain antigen. The cut-off points for the serological tests were determined by a receiver operator characteristic curve. Results: The DB and DID tests showed similar accuracy, but the DB identified lower antibody concentrations. Cross-reactions were absent in the DB assay. In the relapse diagnoses, DB exhibited much higher sensitivity (90%) than DID (30%). Conclusions: A DB assay is easier and faster than a DID test to be performed; DB and DID tests show the same accuracy, while blood qPCR is not recommended in the diagnosis at the time of admission; cross-reactions were not observed with other systemic diseases; DB and DID tests are useful for treatment monitoring PCM patients; and a DB assay is the choice for diagnosing relapse. These findings support the introduction of semi-quantitative DB assays in clinical laboratories. Full article
(This article belongs to the Special Issue Paracoccidioidomycosis)
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9 pages, 1878 KiB  
Communication
Re-Evaluation of the Cross-Reactions of the Antibody against the Causative Agent for Paracoccidioidomycosis Ceti; Paracoccidioides ceti and the Related Fungal Species
by Hikaru Kanegae, Igor Massahiro de Souza Suguiura, Rentaro Tashiro, Toshihiro Konno, De-Xing Hou, Ayako Sano, Takeshi Eto, Keiichi Ueda and Md. Amzad Hossain
Microorganisms 2023, 11(10), 2428; https://doi.org/10.3390/microorganisms11102428 - 28 Sep 2023
Viewed by 773
Abstract
Paracoccidioidomycosis ceti (PCM-C) is a chronic granulomatous keloidal dermatitis in cetaceans that has been reported worldwide and is caused by Paracoccidioides ceti. Serological cross-reactions among highly pathogenic fungal infections and related diseases have been reported. However, the true cross-reaction of antibodies against [...] Read more.
Paracoccidioidomycosis ceti (PCM-C) is a chronic granulomatous keloidal dermatitis in cetaceans that has been reported worldwide and is caused by Paracoccidioides ceti. Serological cross-reactions among highly pathogenic fungal infections and related diseases have been reported. However, the true cross-reaction of antibodies against P. ceti has remained unknown due to the use of positive control sera from infected dolphins. This study aimed to re-evaluate antibodies from mechanically dislodged fungal cells in the infected tissue of a PCM-C case and demonstrate the actual cross-reaction. The results revealed a limited cross-reaction between PCM-C and paracoccidioidomycosis, while the antibodies did not react with other pathogens such as Coccidioides posadasii, Histoplasama capsulatum, and Arthrographis kalrae. Thus, the method for evaluation of the antibody against PCM-C is reliable, and there is potential for epidemiological study. Full article
(This article belongs to the Special Issue Paracoccidioidomycosis)
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13 pages, 1536 KiB  
Article
Molecular Phylogenetic Analysis of Paracoccidioides Species Complex Present in Paracoccidioidomycosis Patient Tissue Samples
by Luciana Bonome Zeminian de Oliveira, Amanda Manoel Della Coletta, Taiane Priscila Gardizani, Hans Garcia Garces, Eduardo Bagagli, Luciana Trilles, Ligia Vizeu Barrozo, Sílvio de Alencar Marques, Julio De Faveri and Luciane Alarcão Dias-Melicio
Microorganisms 2023, 11(3), 562; https://doi.org/10.3390/microorganisms11030562 - 23 Feb 2023
Cited by 1 | Viewed by 1156
Abstract
Paracoccidioidomycosis (PCM) is the main and most prevalent systemic mycosis in Latin America, that until recently, it was believed to be caused only by Paracoccidioides brasiliensis (P. brasiliensis). In 2006, researchers described three cryptic species: S1, PS2, PS3, and later, another [...] Read more.
Paracoccidioidomycosis (PCM) is the main and most prevalent systemic mycosis in Latin America, that until recently, it was believed to be caused only by Paracoccidioides brasiliensis (P. brasiliensis). In 2006, researchers described three cryptic species: S1, PS2, PS3, and later, another one, PS4. In 2009, Paracoccidioides lutzii (Pb01-like) was described, and in 2017, a new nomenclature was proposed for the different agents: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), and P. venezuelensis (PS4). These species are not uniformly distributed throughout Latin America and, knowing that more than one cryptic species could coexist in some regions, we aimed to identify those species in patients’ biopsy samples for a better understanding of the distribution and occurrence of these recently described species in Botucatu region. The Hospital of Medical School of Botucatu—UNESP, which is a PCM study pole, is located in São Paulo State mid-west region and is classified as a PCM endemic area. Genotyping analyses of clinical specimens from these patients that have been diagnosed and treated in our Hospital could favor a possible correlation between genetic groups and mycological and clinical characteristics. For this, molecular techniques to differentiate Paracoccidioides species in these biopsies, such as DNA extraction, PCR, and sequencing of three target genes (ITS, CHS2, and ARF) were conducted. All the sequences were analyzed at BLAST to testify the presence of P. brasiliensis. The phylogenetic trees were constructed using Mega 7.0 software and showed that 100% of our positive samples were from S1 cryptic species, therefore P. brasiliensis. This is important data, demonstrating the predominance of this species in the São Paulo State region. Full article
(This article belongs to the Special Issue Paracoccidioidomycosis)
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13 pages, 1840 KiB  
Article
Molecular Interactions of the Copper Chaperone Atx1 of Paracoccidioides brasiliensis with Fungal Proteins Suggest a Crosstalk between Iron and Copper Homeostasis
by Marcos Antonio Batista de Carvalho Júnior, Lana O’Hara Souza Silva, Laurine Lacerda Pigosso, Aparecido Ferreira de Souza, Danize Eukales Menezes Lugo, Dayane Moraes, Kleber Santiago Freitas e Silva, Maristela Pereira and Célia Maria de Almeida Soares
Microorganisms 2023, 11(2), 248; https://doi.org/10.3390/microorganisms11020248 - 18 Jan 2023
Viewed by 1565
Abstract
Paracoccidioides spp. are endemic fungi from Latin America that cause Paracoccidioidomycosis, a systemic disease. These fungi present systems for high-affinity metal uptake, storage, and mobilization, which counteract host nutritional immunity and mitigate the toxic effects of metals. Regarding Cu mobilization, the metallochaperone Atx1 [...] Read more.
Paracoccidioides spp. are endemic fungi from Latin America that cause Paracoccidioidomycosis, a systemic disease. These fungi present systems for high-affinity metal uptake, storage, and mobilization, which counteract host nutritional immunity and mitigate the toxic effects of metals. Regarding Cu mobilization, the metallochaperone Atx1 is regulated according to Cu bioavailability in Paracoccidioides spp., contributing to metal homeostasis. However, additional information in the literature on PbAtx1 is scarce. Therefore, in the present work, we aimed to study the PbAtx1 protein–protein interaction networks. Heterologous expressed PbAtx1 was used in a pull-down assay with Paracoccidioides brasiliensis cytoplasmic extract. Nineteen proteins that interacted with PbAtx1 were identified by HPLC-MSE. Among them, a relevant finding was a Cytochrome b5 (PbCyb5), regulated by Fe bioavailability in Aspergillus fumigatus and highly secreted by P. brasiliensis in Fe deprivation. We validated the interaction between PbAtx1-PbCyb5 through molecular modeling and far-Western analyses. It is known that there is a relationship between Fe homeostasis and Cu homeostasis in organisms. In this sense, would PbAtx1-PbCyb5 interaction be a new metal-sensor system? Would it be supported by the presence/absence of metals? We intend to answer those questions in future works to contribute to the understanding of the strategies employed by Paracoccidioides spp. to overcome host defenses. Full article
(This article belongs to the Special Issue Paracoccidioidomycosis)
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16 pages, 1965 KiB  
Article
Paracoccidioides lutzii Formamidase Contributes to Fungal Survival in Macrophages
by Lana O’Hara Souza Silva, Thalison Rodrigues Moreira, Relber Aguiar Gonçales, Mariana Vieira Tomazett, Juliana Alves Parente-Rocha, Karine Mattos, Juliano Domiraci Paccez, Orville Hernandez Ruiz, Maristela Pereira, Célia Maria de Almeida Soares, Simone Schneider Weber, Vanessa Rafaela Milhomem Cruz-Leite and Clayton Luiz Borges
Microorganisms 2022, 10(10), 2011; https://doi.org/10.3390/microorganisms10102011 - 12 Oct 2022
Cited by 2 | Viewed by 1607
Abstract
Nitrogen is a crucial nutrient for microorganisms that compose essential biomolecules. However, hosts limit this nutrient as a strategy to counter infections, therefore, pathogens use adaptive mechanisms to uptake nitrogen from alternative sources. In fungi, nitrogen catabolite repression (NCR) activates transcription factors to [...] Read more.
Nitrogen is a crucial nutrient for microorganisms that compose essential biomolecules. However, hosts limit this nutrient as a strategy to counter infections, therefore, pathogens use adaptive mechanisms to uptake nitrogen from alternative sources. In fungi, nitrogen catabolite repression (NCR) activates transcription factors to acquire nitrogen from alternative sources when preferential sources are absent. Formamidase has been related to nitrogen depletion in Aspergillus nidulans through formamide degradation to use the released ammonia as a nitrogen source. In Paracoccidioides spp., formamidase is highly expressed in transcriptomic and proteomic analyses. Here, we aim to investigate the importance of formamidase to Paracoccidioides lutzii. Thereby, we developed a P. lutzii silenced strain of fmd gene (AsFmd) by antisense RNA technology using Agrobacterium tumefaciens-mediated transformation (ATMT). The AsFmd strain led to increased urease expression, an enzyme related to nitrogen assimilation in other fungi, suggesting that P. lutzii might explore urease as an alternative route for ammonia metabolism as a nitrogen source. Moreover, formamidase was important for fungal survival inside macrophages, as fungal recovery after macrophage infection was lower in AsFmd compared to wild-type (WT) strain. Our findings suggest potential alternatives of nitrogen acquisition regulation in P. lutzii, evidencing formamidase influence in fungal virulence. Full article
(This article belongs to the Special Issue Paracoccidioidomycosis)
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