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Journal of Fungi (Basel, Switzerland) Sep 2023Paracoccidioidomycosis (PCM) is a neglected endemic mycosis in Latin America. Most cases occur in Brazil. It is classified as PCM infection and PCM disease and is...
Paracoccidioidomycosis (PCM) is a neglected endemic mycosis in Latin America. Most cases occur in Brazil. It is classified as PCM infection and PCM disease and is subdivided into chronic (adult type) or acute (juvenile type) disease, with the latter being less frequent and more severe. In 2016, we reported an increase in the numbers of patients diagnosed with acute PCM after a highway's construction. We conducted a study at INI-Fiocruz, a reference center for infectious diseases, including endemic mycoses, in Rio de Janeiro, Brazil, aiming to deepen the analysis of this new clinical and epidemiological profile of PCM. The authors developed a retrospective study including 170 patients diagnosed with PCM between 2010 and 2019. There was an increase in the number of atypical and severe forms, starting in 2014. In subsequent years, we detected a higher incidence of adverse outcomes with patients requiring more hospitalizations and an increased mortality rate. We estimate that PCM has become more severe throughout the Rio de Janeiro state, affecting a greater number of young individuals and leading to a greater number of and longer hospitalizations. Surveillance measures and close monitoring of future notification data in the state, with emphasis on children, adolescents, and young adults are necessary for a better understanding of the perpetuation of this public health challenge.
PubMed: 37755054
DOI: 10.3390/jof9090946 -
Frontiers in Fungal Biology 2023In fungal pathogens the cell wall plays an important role in host-pathogen interactions because its molecular components (e.g., polysaccharides and proteins) may trigger...
In fungal pathogens the cell wall plays an important role in host-pathogen interactions because its molecular components (e.g., polysaccharides and proteins) may trigger immune responses during infection. GPI-anchored proteins represent the main protein class in the fungal cell wall where they can perform several functions, such as cell wall remodeling and adhesion to host tissues. Genomic analysis has identified the complement of GPI-anchored proteins in many fungal pathogens, but the function has remained unknown for most of them. Here, we conducted an RNA expression analysis of GPI-anchored proteins of which causes paracoccidioidomycosis (PCM), an important human systemic mycosis endemic in Latin America. The expression of the GPI-anchored proteins was analyzed by quantitative PCR in both the mycelium and yeast forms. qPCR analysis revealed that the transcript levels of 22 of them were increased in hyphae and 10 in yeasts, respectively, while 14 did not show any significant difference in either form. Furthermore, we cloned 46 open reading frames and purified their corresponding GPI-anchored proteins in the budding yeast. Immunoblot and ELISA analysis of four purified GPI-anchored proteins revealed immune reactivity of these proteins against sera obtained from PCM patients. The information obtained in this study provides valuable information about the expression of many GPI-anchored proteins of unknown function. In addition, based on our immune analysis, some GPI-anchored proteins are expressed during infection and therefore, they might serve as good candidates for the development of new diagnostic methods.
PubMed: 37746134
DOI: 10.3389/ffunb.2023.1243475 -
Future Medicinal Chemistry Sep 2023The development of safe and effective therapies for treating paracoccidioidomycosis using computational strategies were employed to discover anti- compounds. We 1)...
The development of safe and effective therapies for treating paracoccidioidomycosis using computational strategies were employed to discover anti- compounds. We 1) collected, curated and integrated the largest library of compounds tested against spp.; 2) employed a similarity search to virtually screen the ChemBridge database and select nine compounds for experimental evaluation; 3) performed an experimental evaluation to determine the minimum inhibitory concentration and minimum fungicidal concentration as well as cytotoxicity; and 4) employed computational tools to identify potential targets for the most active compounds. Seven compounds presented activity against spp. These compounds are new hits with a predicted mechanisms of action, making them potentially attractive to develop new compounds.
Topics: Antifungal Agents; Paracoccidioides; Cheminformatics; Paracoccidioidomycosis; Microbial Sensitivity Tests
PubMed: 37727967
DOI: 10.4155/fmc-2022-0288 -
Biomedica : Revista Del Instituto... Aug 2023The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.
INTRODUCTION
The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.
OBJECTIVE
To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis.
MATERIALS AND METHODS
The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 °C ± 1 °C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after , 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors.
RESULTS
Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time.
CONCLUSION
The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.
Topics: Humans; Paracoccidioides; Cost-Benefit Analysis; Paracoccidioidomycosis; Reproducibility of Results; Blood Group Antigens; Antibodies
PubMed: 37721912
DOI: 10.7705/biomedica.6874 -
Biomedica : Revista Del Instituto... Aug 2023Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis.
INTRODUCTION
Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. Climate change and host migration emphasize the need to optimize this infection diagnosis.
OBJECTIVE
To evaluate the implementation of Paracoccidioides spp. DNA detection in the mycological diagnosis of patients with suspected paracoccidioidomycosis.
MATERIALS AND METHODS
It is a retrospective study with laboratory data from patients with clinical suspicion of paracoccidioidomycosis, who consulted a university hospital from a non-endemic area.
RESULTS
We analyzed the laboratory results of samples from 19 patients with suspected paracoccidioidomycosis. Seventeen out of 19 patients were born in or had visited an endemic area in Latin America. Fourteen adult male patients were confirmed to have paracoccidioidomycosis by conventional diagnosis: the direct examination was positive in 12 samples while fungal growth was found only in 4. Anti-Paracoccidioides spp. antibodies were detected in 10 patients, 8 of them with proven paracoccidioidomycosis. Nested PCR for Paracoccidioides spp. detection was performed on clinical samples from 14 patients, and positive results were obtained for 9 out of 10 patients with the conventional diagnosis of paracoccidioidomycosis.
CONCLUSIONS
The incorporation of molecular techniques to detect Paracoccidioides spp. DNA complements the conventional diagnosis of paracoccidioidomycosis. This tool allows the prescription of antifungal treatment in those cases where the fungus is not observed in the clinical samples.
Topics: Hospitals; Polymerase Chain Reaction; Tolnaftate
PubMed: 37721907
DOI: 10.7705/biomedica.6888 -
Biomedica : Revista Del Instituto... Aug 2023Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. The most frequent form involves a chronic compromise of the lungs, skin, and mucosa. The patient...
Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. The most frequent form involves a chronic compromise of the lungs, skin, and mucosa. The patient started with a single oral lesion that lasted for several years. The absence of other symptoms pointed out a possible malignant neoplasm, specifically a squamous cell carcinoma. Differentiation between both diagnoses –fungal infection and carcinoma– depends on the results of the direct examination, the histopathological study, and the initial and subsequent cultures. However, in this case, those findings were not conclusive. The coexistence of both diagnoses is frequent and increases the diagnostic challenge. After several consultations and tests, direct examination, immunodiffusion and real-time PCR findings the multifocal chronic paracoccidioidomycosis diagnosis was confirmed. This case warns about a systematical absence of clinical suspicion of endemic mycoses before the appereance of mucocutaneous lesions, which can be produced by fungi like Paracoccidioides spp, and the importance of considering those mycoses among the differential diagnoses.
Topics: Humans; Paracoccidioidomycosis; Hyperplasia; Carcinoma, Squamous Cell; Skin; Cell Differentiation
PubMed: 37721905
DOI: 10.7705/biomedica.6899 -
Biomedica : Revista Del Instituto... Aug 2023
PubMed: 37721901
DOI: 10.7705/biomedica.6977 -
Biomedica : Revista Del Instituto... Aug 2023
PubMed: 37721895
DOI: 10.7705/biomedica.7219 -
Biochimie Mar 2024The pathogen Paracoccidioides lutzii (Pb01) is found in South America countries Colombia, Ecuador, Venezuela and Brazil, especially in the central, west, and north...
The pathogen Paracoccidioides lutzii (Pb01) is found in South America countries Colombia, Ecuador, Venezuela and Brazil, especially in the central, west, and north regions of the latter. It belongs to the Ajellomycetaceae family, Onygenales order, and is typically thermodimorphic, presenting yeast cells when it grows in animal tissues, but mycelia when in the environment, where it produces the infectious propagule. This fungus is one of the etiologic agents of Paracoccidioidomycosis (PCM), the most important endemic fungal infection in Latin America. Investigations on its genome have contributed to a better understanding about its metabolism and revealed the complexity of several metabolic glycolytic pathways. Glyceraldehyde-3-Phosphate Dehydrogenase from Paracoccidioides lutzii (PlGAPDH) is considered a moonlighting protein and participates in several biological processes of this pathogen. The enzyme was expressed and purified, as seen in SDS-PAGE gel, crystallized and had its three dimensional structure (3D) determined in complex with NAD, a sulphate ion and d-galactonic acid, therefore, a type of 'GAA site'. It is the first GAPDH structure to show this chemical type in this site and how this protein can bind an acid derived from oxidation of a linear hexose.
Topics: Animals; Paracoccidioides; Paracoccidioidomycosis; Brazil; Sugars
PubMed: 37709188
DOI: 10.1016/j.biochi.2023.09.013 -
PLoS Neglected Tropical Diseases Sep 2023The occurrence of acute paracoccidioidomycosis (PCM) in urban areas of the Rio de Janeiro state, Brazil, has emerged in recent years. Therefore, young populations,...
The occurrence of acute paracoccidioidomycosis (PCM) in urban areas of the Rio de Janeiro state, Brazil, has emerged in recent years. Therefore, young populations, including pregnant women, are at a higher risk of infection. Furthermore, young women undergoing itraconazole treatment for PCM have increased chances to get pregnant because this medication may reduce the effectiveness of contraceptives. Acute PCM is invasive, reaching abdominal organs, posing a maternal-fetal risk. PCM treatment in pregnant women is also challenging due to the teratogenicity associated with the currently available oral drugs. There are scarce studies on PCM and pregnancy, mainly consisting of case reports and experimental murine models that highlight the severity of this association. We conducted a database research at a PCM reference center in Rio de Janeiro state from 1980 to 2020. We included patients diagnosed with PCM who were pregnant shortly before, at admission, or at any moment of their PCM follow-up care. Data related to pregnancy, childbirth, and the newborn were obtained from the Brazilian official public databases. We also reviewed the epidemiological and clinical features of these patients. During the study period, we identified 18 pregnant patients, with a median age of 26 years (range: 16-38). Among these cases, six (33.3%) were detected in the last 5 years, and 14 (77.8%) presented acute PCM, supporting the recent shift in the epidemiological profile towards acute PCM. Most pregnancies occurred during PCM treatment (n = 11, 61.1%), which led to challenges in the therapeutic management. Maternal-fetal complications occurred in some of these cases, including vaginal bleeding (n = 1), preeclampsia (n = 1), prematurity (n = 2), low birth weight (n = 4), and fetal deaths (n = 2). PCM during pregnancy presents a significant public health concern in the context of the emergence of acute PCM in urban areas.
Topics: Humans; Female; Animals; Mice; Pregnancy; Adolescent; Young Adult; Adult; Paracoccidioidomycosis; Brazil; Cohort Studies; Itraconazole; Databases, Factual
PubMed: 37708219
DOI: 10.1371/journal.pntd.0011645