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Frontiers in Cellular and Infection... 2022Fungi of the genus are the etiological agents of the systemic mycosis paracoccidioidomycosis and, when in the host, they find a challenging environment that is scarce...
Fungi of the genus are the etiological agents of the systemic mycosis paracoccidioidomycosis and, when in the host, they find a challenging environment that is scarce in nutrients and micronutrients, such as Fe, which is indispensable for the survival of the pathogen. Previous studies have shown that fungi of this genus, in response to Fe deprivation, are able to synthesize and capture siderophores (Fe chelators), use Fe-containing host proteins as a source of the metal, and use a non-canonical reductive pathway for Fe assimilation. Despite all of these findings, there are still gaps that need to be filled in the pathogen response to metal deprivation. To contribute to the knowledge related to this subject, we obtained the exoproteome of (18) undergoing Fe deprivation and by nanoUPLC-MS. One hundred forty-one proteins were identified, and out of these, 64 proteins were predicted to be secreted. We also identified the regulation of several virulence factors. Among the results, we highlight Cyb5 as a secreted molecule of in the exoproteome obtained during Fe deprivation. Cyb5 is described as necessary for the Fe deprivation response of and Experimental data and molecular modeling indicated that Cyb5 can bind to Fe ions , suggesting that it can be relevant in the arsenal of molecules related to iron homeostasis in .
Topics: Aspergillus fumigatus; Iron; Paracoccidioides; Paracoccidioidomycosis; Saccharomyces cerevisiae; Siderophores
PubMed: 35719340
DOI: 10.3389/fcimb.2022.903070 -
Frontiers in Cellular and Infection... 2020The immune response against fungal infections is complex and exhibits several factors involving innate elements that participate in the interaction with the fungus. The... (Review)
Review
The immune response against fungal infections is complex and exhibits several factors involving innate elements that participate in the interaction with the fungus. The innate immune system developed pattern recognition receptors that recognize different pathogen-associated molecular patterns present both on the surface of the fungi cell wall and on their genetic material. These receptors have the function of activating the innate immune response and regulating a subsequent adaptive immune response. Among pattern recognition receptors, the family of Toll-like receptors and C-type lectin receptors are the best described and characterized, they act directly in the recognition of pathogen-associated molecular patterns expressed on the wall of the fungus and consequently in directing the immune response. In recent years, the role of intracellular pattern recognition receptors (TLR3, TLR7, TLR8, and TLR9) has become increasingly important in the pathophysiology of some mycoses, as paracoccidioidomycosis, cryptococcosis, aspergillosis, and candidiasis. The recognition of nucleic acids performed by these receptors can be essential for the control of some fungal infections, as they can be harmful to others. Therefore, this review focuses on highlighting the role played by intracellular pattern recognition receptors both in controlling the infection and in the host's susceptibility against the main fungi of medical relevance.
Topics: Fungi; Humans; Immunity, Innate; Mycoses; Receptors, Pattern Recognition; Toll-Like Receptors
PubMed: 33194839
DOI: 10.3389/fcimb.2020.591970 -
Revista Do Instituto de Medicina... Sep 2015Paracoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P.... (Review)
Review
Paracoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.
Topics: Animals; Antigens, Fungal; Antigens, Neoplasm; Fungal Vaccines; Glycoproteins; Humans; Mice; Paracoccidioides; Paracoccidioidomycosis; Peptide Fragments; Vaccines, DNA
PubMed: 26465365
DOI: 10.1590/S0036-46652015000700005 -
Respiration; International Review of... 2018Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood.... (Review)
Review
Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood. Diagnosis and management remain challenging, especially in low-prevalence settings, where disease awareness is lacking. The main challenges include the variability of clinical presentation, the fastidious and slow-growing nature of the fungal pathogens, the paucity of diagnostic tests, and the lack of options and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis are restricted to the Americas only, and while histoplasmosis and blastomycosis also occur predominantly in the Americas, these mycoses have also been reported on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic in tropical and subtropical regions in South-East Asia and southern China. Systemic endemic mycoses causing pulmonary disease are usually acquired via the airborne route by inhalation of fungal spores. Infections can range from asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated diseases. Skin involvement is frequent in patients with paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis and manifests as localized lesions or diffuse nodules in disseminated disease, but can also occur with other endemic mycoses. Culture and/or characteristic histopathology from clinical samples is the diagnostic standard for endemic mycoses. Immunological assays are often not available for the diagnosis of most endemic mycoses and molecular amplification methods for the detection of fungal nucleic acids are not standardized at present. The first-line treatment for mild to moderate histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis is itraconazole. Severe illness is treated with amphotericin B. Patients with severe coccidioidomycosis should receive fluconazole. Treatment duration depends on the specific endemic mycosis, the severity of disease, and the immune status of the patient, ranging between 6 weeks and lifelong treatment.
Topics: Adult; Antifungal Agents; Endemic Diseases; Female; Humans; Itraconazole; Lung Diseases, Fungal; Male; Middle Aged; Radiography, Thoracic
PubMed: 29953992
DOI: 10.1159/000489501 -
Revista Do Instituto de Medicina... Sep 2015Research on Paracoccidioides brasiliensis has centered in the yeast cell probably because of the lack of distinctive features in the mycelium. In 1942 and for the first... (Review)
Review
Research on Paracoccidioides brasiliensis has centered in the yeast cell probably because of the lack of distinctive features in the mycelium. In 1942 and for the first time, lateral conidia were noticed in the fungus' hyphae. Later on, Brazilian, Venezuelan and Argentinean researchers described "aleurias" when the fungus was grown in natural substrates. In 1970 authors became interested in the conidia and were able to obtain them in large numbers and treat them as individual units. Their shape and size were defined and the presence of all the elements of a competent eukaryotic cell were demonstrated. Conidia exhibited thermal dimorphism and, additionally, when given intranasally to BALB/c male mice, they converted into yeasts in the lungs and produce progressive pulmonary lesions with further dissemination to other organs. Studies on the phagocyte-conidia interaction were revealing and showed that these versatile structures allow a better understanding of the host- P. brasiliensis interactions.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Lung Diseases, Fungal; Male; Mice; Mice, Inbred BALB C; Paracoccidioides; Paracoccidioidomycosis; Spores, Fungal
PubMed: 26465363
DOI: 10.1590/S0036-46652015000700003 -
Journal of Fungi (Basel, Switzerland) Feb 2021The dimorphic fungi of the genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in... (Review)
Review
The dimorphic fungi of the genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of spp. This review describes the most relevant biological features of spp., including aspects of the phylogeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.
PubMed: 33557381
DOI: 10.3390/jof7020116 -
Virulence 2015Fungi are among the most common microbes encountered by humans. More than 100, 000 fungal species have been described in the environment to date, however only a few... (Review)
Review
Fungi are among the most common microbes encountered by humans. More than 100, 000 fungal species have been described in the environment to date, however only a few species cause disease in humans. Fungal infections are of particular importance to immunocompromised hosts in whom disease is often more severe, especially in those with impaired cell-mediated immunity such as individuals with HIV infection, hematologic malignancies, or those receiving TNF-α inhibitors. Nevertheless, environmental disturbances through natural processes or as a consequence of deforestation or construction can expose immunologically competent people to a large number of fungal spores resulting in asymptomatic acquisition to life-threatening disease. In recent decades, the significance of the innate immune system and more importantly the role of dendritic cells (DC) have been found to play a fundamental role in the resolution of fungal infections, such as in dimorphic fungi like Histoplasma and Paracoccidioides. In this review article the general role of DCs will be illustrated as the bridge between the innate and adaptive immune systems, as well as their specific interactions with these 2 dimorphic fungi.
Topics: Animals; Dendritic Cells; Histoplasma; Histoplasmosis; Host-Pathogen Interactions; Humans; Immunity, Cellular; Immunity, Innate; Paracoccidioides; Paracoccidioidomycosis
PubMed: 25933034
DOI: 10.4161/21505594.2014.965586 -
Radiologia Brasileira 2018Pulmonary fungal infections, which can be opportunistic or endemic, lead to considerable morbidity and mortality. Such infections have multiple clinical presentations... (Review)
Review
Pulmonary fungal infections, which can be opportunistic or endemic, lead to considerable morbidity and mortality. Such infections have multiple clinical presentations and imaging patterns, overlapping with those of various other diseases, complicating the diagnostic approach. Given the immensity of Brazil, knowledge of the epidemiological context of pulmonary fungal infections in the various regions of the country is paramount when considering their differential diagnoses. In addition, defining the patient immunological status will facilitate the identification of opportunistic infections, such as those occurring in patients with AIDS or febrile neutropenia. Histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis usually affect immunocompetent patients, whereas aspergillosis, candidiasis, cryptococcosis, and pneumocystosis tend to affect those who are immunocompromised. Ground-glass opacities, nodules, consolidations, a miliary pattern, cavitary lesions, the halo sign/reversed halo sign, and bronchiectasis are typical imaging patterns in the lungs and will be described individually, as will less common lesions such as pleural effusion, mediastinal lesions, pleural effusion, and chest wall involvement. Interpreting such tomographic patterns/signs on computed tomography scans together with the patient immunological status and epidemiological context can facilitate the differential diagnosis by narrowing the options.
PubMed: 30369659
DOI: 10.1590/0100-3984.2017.0223 -
Journal of Fungi (Basel, Switzerland) Apr 2022This review discusses the inclusion of sex and gender variables in studies of fungal infections in humans at the pathogen, host, and antifungal trial levels. The mating... (Review)
Review
This review discusses the inclusion of sex and gender variables in studies of fungal infections in humans at the pathogen, host, and antifungal trial levels. The mating type of some fungi, or perhaps more likely the absence of the other, appears to be associated with some infections. Sexual and parasexual reproduction of some fungi is an important mechanism for the development of antifungal drug resistance. Host sex or gender influences the incidence of some infections such as aspergillosis, cryptococcosis, paracoccidioidomycosis, dermatophytosis, and candidiasis due to differences in immune response, behavior, and awareness for early detection and treatment. Participant sex (and age) is relevant not only in clinical antifungal trials but also in preclinical studies. The dimensions of sex and gender are important determinants throughout the fungal infection process and in approaches to prevent or treat these infections, as well as in development of antifungal drugs. Failure to consider sex and gender may be detrimental to the holistic understanding of the processes involved in fungal infection.
PubMed: 35628717
DOI: 10.3390/jof8050461 -
Brazilian Journal of Microbiology :... Sep 2023Paracoccidioidomycosis (PCM) is a systemic fungal disease caused by the thermodimorphic fungi Paracoccidioides spp. Their distribution is highly variable....
BACKGROUND AND OBJECTIVE
Paracoccidioidomycosis (PCM) is a systemic fungal disease caused by the thermodimorphic fungi Paracoccidioides spp. Their distribution is highly variable. Paracoccidioides lutzii is predominantly found in North and Middle-West Brazil and Ecuador. This study evaluated the clinicopathological characteristics of 10 patients diagnosed with PCM caused by P. lutzii in a reference center located in southeastern Brazil.
DESIGN
Double immunodiffusion assay (DID) was used to investigate 35 patients' sera with negative serology for P. brasiliensis against a P. lutzii CFA (cell-free antigen).
RESULTS
Out of the 35 retested patients, 10 (28.6%) were positive for P. lutzii CFA. Four patients did not report any displacement to P. lutzii endemic areas. Our results reinforce the importance of using different antigens when testing patients with clinical manifestations of PCM and negative serological tests for P. brasiliensis, primarily in cases of the report of displacement to or former residence in P. lutzii endemic regions.
CONCLUSIONS
The availability of tests for different Paracoccidioides species antigens is fundamental for reaching an adequate diagnosis, patient follow-up, and definition of prognosis.
Topics: Humans; Paracoccidioidomycosis; Paracoccidioides; Brazil; Antigens, Fungal
PubMed: 37289316
DOI: 10.1007/s42770-023-01019-w