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Future Microbiology Nov 2023To access the metabolic changes caused by a chalcone derivative () through a proteomic approach. Proteomic analysis was performed after 9 h of yeast () cell...
To access the metabolic changes caused by a chalcone derivative () through a proteomic approach. Proteomic analysis was performed after 9 h of yeast () cell incubation with the at MIC. The proteomic findings were validated through and assays. Exposure to the compound led to the downregulation of proteins associated with glycolysis and gluconeogenesis, β-oxidation, the citrate cycle and the electron transport chain. caused an energetic imbalance in the fungus metabolism and deep oxidative stress. Additionally, the molecular docking approach pointed to this molecule as a putative competitive inhibitor of DHPS.
Topics: Paracoccidioides; Proteomics; Molecular Docking Simulation; Oxidative Stress; Oxidation-Reduction; Paracoccidioidomycosis
PubMed: 37424510
DOI: 10.2217/fmb-2022-0150 -
Mycoses Jan 2024Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, with a high incidence in Brazil, Colombia and Venezuela, and constitutes a serious public...
BACKGROUND
Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, with a high incidence in Brazil, Colombia and Venezuela, and constitutes a serious public health problem, a frequent cause of morbidity and disability for work. Some mechanisms of cell death are described as important tools in infectious processes. When apoptosis is blocked, RIPK (Receptor-interacting protein kinase) 3 dependent, a caspase-independent form of cell death, can limit the replication and spread of pathogens. Some molecules that mediate necroptosis include RIPK3 and have been extensively studied due to their signalling mechanism and pathological function. RIPK3 activates NLRP1 and NLRP3-mediated inflammasome formation. Caspase-1 has an important role in processing the cytokines ILβ and IL18 to their active form. Such molecules are part of the inflammasome characterization, whose caspase-1-dependent activation promotes the death of pyroptotic cells and the secretion of proinflammatory cytokines. Knowledge about the mechanisms of pathogen-mediated cell death can be useful for understanding of the pathogenesis of infections and inflammatory conditions.
OBJECTIVE
The objective of this work was to identify the mechanisms of programmed cell death and inflammasome components in human oral mucosal lesions of paracoccidioidomycosis through immunohistochemical methods and identification of RIPK-3, IL1β, IL18, NLRP-1 and caspase-1. Thirty specimens were included, and a histopathological analysis of the lesions was performed using haematoxylin-eosin staining.
RESULTS
Our results on in situ expression of inflammasome elements and programmed cell death showed increased expression of IL-1β, NLRP-1, caspase-1 and RIPK-3. We suggest that inflammasome complex participate in the immunopathogenesis in paracoccidioidomycosis oral lesions in an interplay with RIPK3.
Topics: Humans; Inflammasomes; Interleukin-18; Paracoccidioidomycosis; Apoptosis; Caspase 1; Cytokines
PubMed: 37837228
DOI: 10.1111/myc.13662 -
Current Opinion in Pediatrics Apr 2024Invasive fungal infection (IFI) in children is a growing problem with crescent morbidity and mortality, well recognized in developed countries, affecting mainly... (Review)
Review
Overview of invasive fungal infections in children in South America - the threat of resistant Candida species and the role of climate change in the new geographic distribution of endemic systemic mycosis.
PURPOSE OF REVIEW
Invasive fungal infection (IFI) in children is a growing problem with crescent morbidity and mortality, well recognized in developed countries, affecting mainly immunocompromised children, including neonates and children in intensive care units. The burden of IFI in South American children is less well comprehended. In addition, the current epidemiology of endemic systemic mycoses in children may have changed over time.
RECENT FINDINGS
Candida spp. infections are very prevalent in South America hospitalized children, especially in neonates, in a rate far superior compared to developed countries. C. auris, has already been responsible for outbreaks in neonates and children in Venezuela and Colombia. Sporotrichosis is well established as an urban zoonosis in impoverish families. Paracoccidioidomycosis and histoplasmosis are affecting new areas of Brazil, probably due to climate change, deforestation, and human migration.
SUMMARY
This review aims to unveil the real dimension of these infections in South American children. Hopefully, the awareness brought by this review will help healthcare professionals to recognize IFI more easily and it will provide support for getting more resources for IFI treatment and prevention.
Topics: Child; Infant, Newborn; Humans; Candida; Climate Change; Mycoses; Invasive Fungal Infections; South America
PubMed: 38299979
DOI: 10.1097/MOP.0000000000001327 -
Mycoses Jul 2024The impact of COVID-19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the...
The impact of COVID-19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the pandemic declaration, 285 proven PCM patients were registered. No association between both diseases was documented. PCM frequency decreased to extremely low levels in 2020. Mandatory social isolation and the emotional and psychological effects generated under pandemic circumstances led to delays in diagnosis, severe disseminated cases, and other challenges for diagnosis in subsequent years. Probable underdiagnosis should be considered due to the overlap of clinical manifestations, the low index of suspicion and the lack of sensitive diagnostic tools.
Topics: Paracoccidioidomycosis; Humans; COVID-19; Argentina; Male; Adult; Middle Aged; Female; SARS-CoV-2; Aged; Young Adult; Pandemics; Adolescent; Delayed Diagnosis
PubMed: 38946016
DOI: 10.1111/myc.13761 -
Future Microbiology Nov 2023Dermatophytosis, paracoccidioidomycosis and sporotrichosis are mycoses caused by different fungal species with significant prevalence in Brazil and other countries. In...
Dermatophytosis, paracoccidioidomycosis and sporotrichosis are mycoses caused by different fungal species with significant prevalence in Brazil and other countries. In some situations, they affect quality of life, especially in the most vulnerable populations. Antifungal drug therapy is the conventional treatment for these diseases, although some difficulties may occur. Adjunctive use of antimicrobial photodynamic therapy (aPDT) may reduce these challenges. Three patients were treated with aPDT and conventional antifungals. In all cases, the patients did not report pain, discomfort or side effects during or after the aPDT intervention. The adjunctive use of aPDT in the cases presented proved to be a safe, low-cost tool that may be promising for the treatment of different mycoses.
Topics: Humans; Methylene Blue; Photosensitizing Agents; Quality of Life; Photochemotherapy; Mycoses; Anti-Infective Agents
PubMed: 37702055
DOI: 10.2217/fmb-2023-0074 -
Tropical Medicine & International... Sep 2023To analyse the records of male hospitalisation for fungal infections, including their spatial distribution and the main invasive epidemiological and sociodemographic...
OBJECTIVE
To analyse the records of male hospitalisation for fungal infections, including their spatial distribution and the main invasive epidemiological and sociodemographic characteristics in the State of Paraná, Brazil.
METHODS
Spatial analysis based on data from male admission records for invasive fungal infections (IFIs) in the State of Paraná, from 2015 to 2019. Data were taken from the hospital records obtained in the Hospital Information System of the Unified Health System, being collected, georeferenced and analysed to infer the existence of autocorrelation with the hospitalisation rates in the state.
RESULTS
From 2015 to 2019, there were 385 cases of IFIs in men, being more prevalent in white individuals aged 61-70 years. We observed that the metropolitan, southeast, central-eastern, north-central, northwestern and western regions formed high-high clusters, with regions with a high number of registered cases. In the regression, there was an association with socioeconomic and demographic factors that showed a correlation with the rates of hospitalisation for IFIs.
CONCLUSION
The study draws attention to Paraná as an endemic region for paracoccidioidomycosis, in addition to presenting high rates of nosocomial fungal infections. We also emphasise the importance of compulsory notification in the state and in the country to gain greater control over the incidence and prevalence of cases and to incentivise the creation of public policies for the prevention of IFIs.
Topics: Humans; Male; Brazil; Mycoses; Invasive Fungal Infections; Paracoccidioidomycosis; Spatial Analysis
PubMed: 37559424
DOI: 10.1111/tmi.13925 -
Frontiers in Cellular and Infection... 2023Granulomas are important immunological structures in the host defense against the fungus , the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous...
Granulomas are important immunological structures in the host defense against the fungus , the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeasts present in the pulmonary granulomas of PCM aiming to identify relevant genes and proteins that act under stressing conditions. C57BL/6 mice were infected with 1x10 yeasts and after 8- and 12-weeks of infection, granulomatous lesions were obtained for extraction of fungal and murine RNAs and fungal proteins. Dual transcriptional profiling was done comparing lung cells and yeasts from granulomas with uninfected lung cells and the original yeast suspension used in the infection, respectively. Mouse transcripts indicated a lung malfunction, with low expression of genes related to muscle contraction and organization. In addition, an increased expression of transcripts related to the activity of neutrophils, eosinophils, macrophages, lymphocytes as well as an elevated expression of IL-1β, TNF-α, IFN-γ, IL-17 transcripts were observed. The increased expression of transcripts for CTLA-4, PD-1 and arginase-1, provided evidence of immune regulatory mechanisms within the granulomatous lesions. Also, our results indicate iron as a key element for the granuloma to function, where a high number of transcripts related to fungal siderophores for iron uptake was observed, a mechanism of fungal virulence not previously described in granulomas. Furthermore, transcriptomics and proteomics analyzes indicated a low fungal activity within the granuloma, as demonstrated by the decreased expression of genes and proteins related to energy metabolism and cell cycle.
Topics: Animals; Mice; Paracoccidioides; Proteomics; Mice, Inbred C57BL; Paracoccidioidomycosis; Iron; Immunity; Granuloma
PubMed: 37868350
DOI: 10.3389/fcimb.2023.1268959 -
Dectin-2 is critical for phagocyte function and resistance to Paracoccidioides brasiliensis in mice.Medical Mycology Nov 2023Germline-encoded pattern recognition receptors, particularly C-type lectin receptors (CLRs), are essential for phagocytes to sense invading fungal cells. Among CLRs,...
Germline-encoded pattern recognition receptors, particularly C-type lectin receptors (CLRs), are essential for phagocytes to sense invading fungal cells. Among CLRs, Dectin-2 (encoded by Clec4n) plays a critical role in the antifungal immune response as it recognizes high-mannose polysaccharides on the fungal cell wall, triggering phagocyte functional activities and ultimately determining adaptive responses. Here, we assessed the role of Dectin-2 on the course of primary Paracoccidioides brasiliensis systemic infection in mice with Dectin-2-targeted deletion. Paracoccidioides brasiliensis constitutes the principal etiologic agent of paracoccidioidomycosis, the most prominent invasive mycosis in Latin American countries. The deficiency of Dectin-2 resulted in shortened survival rates, high lung fungal burden, and increased lung pathology in mice infected with P. brasiliensis. Consistently, dendritic cells (DCs) from mice lacking Dectin-2 infected ex vivo with P. brasiliensis showed impaired secretion of several proinflammatory and regulatory cytokines, including TNF-α, IL-1β, IL-6, and IL-10. Additionally, when cocultured with splenic lymphocytes, DCs were less efficient in promoting a type 1 cytokine pattern secretion (i.e., IFN-γ). In macrophages, Dectin-2-mediated signaling was required to ensure phagocytosis and fungicidal activity associated with nitric oxide production. Overall, Dectin-2-mediated signaling is critical to promote host protection against P. brasiliensis infection, and its exploitation might lead to the development of new vaccines and immunotherapeutic approaches.
Topics: Mice; Animals; Paracoccidioides; Phagocytes; Lectins, C-Type; Macrophages; Paracoccidioidomycosis
PubMed: 37960963
DOI: 10.1093/mmy/myad117 -
Journal of Fungi (Basel, Switzerland) Feb 2024The incidence of paracoccidioidomycosis (PCM) varies in Latin America, and it is influenced by environmental factors. This study evaluated the distribution of PCM...
The incidence of paracoccidioidomycosis (PCM) varies in Latin America, and it is influenced by environmental factors. This study evaluated the distribution of PCM acute/subacute form (AF) cases and their correlation with geoclimatic factors in the Mato Grosso do Sul (MS) state. The study included 81 patients diagnosed with the PCM/AF at the University Hospital of the Federal University of Mato Grosso do Sul between January 1980 and February 2022. Geographic coordinates, health microregion of patient's residence, compensated average temperature, relative air humidity (RH), El Niño Southern Oscillation (ENSO), and average global temperature were analyzed. The highest incidence was observed in the Aquidauana (7/100,000 inhabitants), while Campo Grande, the state's capital, had the highest number (n = 34; 42.4%) and density (4.4 cases/km) of cases. The number of cases increased during extended periods of the El Niño phenomenon. A positive correlation was found between higher RH and PCM/AF cases. Most PCM/AF cases were found in areas with loamy soils and RH ranging from 60.8 to 73.6%. In MS, the health microregions of PCM/AF patients are characterized by deforestation for agricultural and pasture use, coupled with loamy soils and specific climatic phenomena leading to higher soil humidity.
PubMed: 38535174
DOI: 10.3390/jof10030165 -
Journal of Fungi (Basel, Switzerland) Aug 2023The treatment of paracoccidioidomycosis (PCM) is a challenge, and the discovery of new antifungal compounds is crucial. The phenacylideneoxindoles exhibited promising...
BACKGROUND
The treatment of paracoccidioidomycosis (PCM) is a challenge, and the discovery of new antifungal compounds is crucial. The phenacylideneoxindoles exhibited promising antifungal activity against spp., but their mode of action remains unknown.
METHODS
Through proteomic analysis, we investigated the effects of (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one on . In addition, we investigated the metabolic alterations of in response to the compound. Furthermore, the effects of the compound on the membrane, ethanol production, and reactive oxygen species (ROS) production were verified.
RESULTS
We identified differentially regulated proteins that revealed significant metabolic reorganization, including an increase in ethanol production, suggesting the activation of alcoholic fermentation and alterations in the rigidity of fungal cell membrane with an increase of the ergosterol content and formation of ROS.
CONCLUSIONS
These findings enhance our understanding of the mode of action and response of to the investigated promising antifungal compound, emphasizing its potential as a candidate for the treatment of PCM.
PubMed: 37623625
DOI: 10.3390/jof9080854