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Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America caused by thermodimorphic fungi of the genus Paracoccidioides. In the last two decades, enhanced understanding of the phylogenetic species concept and molecular variations has led to changes in this genus’ taxonomic classification. Although the impact of the new species on clinical presentation and treatment remains unclear, they can influence diagnosis when serological methods are employed. Further, although the infection is usually acquired in rural areas, the symptoms may manifest years or decades later when the patient might be living in the city or even in another country outside the endemic region. Brazil accounts for 80% of PCM cases worldwide, and its incidence is rising in the northern part of the country (Amazon region), owing to new settlements and deforestation, whereas it is decreasing in the south, owing to agriculture mechanization and urbanization. Clusters of the acute/subacute form are also emerging in areas with major human intervention and climate change. Advances in diagnostic methods (molecular and immunological techniques and biomarkers) remain scarce, and even the reference center’s diagnostics are based mainly on direct microscopic examination. Classical imaging findings in the lungs include interstitial bilateral infiltrates, and eventually, enlargement or calcification of adrenals and intraparenchymal central nervous system lesions are also present. Besides itraconazole, cotrimoxazole, and amphotericin B, new azoles may be an alternative when the previous ones are not tolerated, although few studies have investigated their use in treating PCM.

Paracoccidioidomycosis (PCM) is a systemic fungal infection endemic to Latin America, especially Brazil, where it is considered a neglected occupational disease. Caused by Paracoccidioides spp., PCM presents a wide spectrum of clinical manifestations, ranging from localized to severe disseminated forms. This heterogeneity suggests that host-related factors, including genetic background, may influence disease development. Genetic susceptibility to infectious diseases is key to understanding differences in immune responses. In PCM, variants in immune-related genes such as cytokines and pattern recognition receptors may modulate susceptibility and disease progression. This study aimed to review the literature on the association between single nucleotide variants (SNVs) PCM susceptibility, severity, and clinical outcomes. A systematic review followed PRISMA guidelines, searching databases like MEDLINE (PubMed), Cochrane Library, LILACS, SciELO, Web of Science, and Google Scholar. Keywords related to “Paracoccidioidomycosis” and “SNVs” were used. The review included studies on SNVs and PCM susceptibility. The quality of the evidence was assessed with the Cochrane and Joanna Briggs Institute risk of bias tool. We also performed a meta-analysis of studies utilizing identical SNVs. This study is registered on PROSPERO, number CRD42025646417. Two SNVs, Interleukin 10 ( IL10 ) and Vitamin D Receptor ( VDR ) showed a significant association in individual analyses, but none demonstrated a significant association in the meta-analysis. The main limitations discussed in the studies were insufficient sample size, population heterogeneity, and the composition of control groups. Although some SNVs, particularly in IL10 and VDR, showed significant associations with PCM susceptibility in individual studies, the evidence remains limited. The meta-analyses included only two studies per SNV, resulting in low statistical power and exploratory pooled estimates, largely reflecting small sample sizes, lack of replication, and methodological heterogeneity across studies.

Systemic and endemic mycoses are considered life-threatening respiratory diseases which are caused by a group of dimorphic fungal pathogens belonging to the genera Histoplasma , Coccidioides , Blastomyces , Paracoccidioides , Talaromyces , and the newly described pathogen Emergomyces . T-cell mediated immunity, mainly T helper (Th)1 and Th17 responses, are essential for protection against these dimorphic fungi; thus, IL-17 production is associated with neutrophil and macrophage recruitment at the site of infection accompanied by chemokines and proinflammatory cytokines production, a mechanism that is mediated by some pattern recognition receptors (PRRs), including Dectin-1, Dectine-2, TLRs, Mannose receptor (MR), Galectin-3 and NLPR3, and the adaptor molecules caspase adaptor recruitment domain family member 9 (Card9), and myeloid differentiation factor 88 (MyD88). However, these PRRs play distinctly different roles for each pathogen. Furthermore, neutrophils have been confirmed as a source of IL-17, and different neutrophil subsets and neutrophil extracellular traps (NETs) have also been described as participating in the inflammatory process in these fungal infections. However, both the Th17/IL-17 axis and neutrophils appear to play different roles, being beneficial mediating fungal controls or detrimental promoting disease pathologies depending on the fungal agent. This review will focus on highlighting the role of the IL-17 axis and neutrophils in the main endemic and systemic mycoses: histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis.

The search for new compounds with activity against Paracoccidioides , etiologic agents of Paracoccidioidomycosis (PCM), is extremely necessary due to the current scenario of the available therapeutic arsenal. Treatment is restricted to three classes of antifungals with side effects. Curcumin is a polyphenol with antifungal effects that is extracted from Curcuma longa . The present work aimed to evaluate the activity of curcumin in different species of Paracoccidioides and to evaluate the potential molecular targets of curcumin using computational strategies. In addition, interactions with classic antifungals used in the treatment of PCM were evaluated. Curcumin inhibits the growth of Paracoccidioides spp. exerting a fungicidal effect. The combination of curcumin with amphotericin B, co-trimoxazole, and itraconazole showed a synergistic or additive interaction. Molecular targets as superoxide dismutase, catalase, and isocitrate lyase were proposed based on in silico approaches. Curcumin affects the fungal plasma membrane and increases the production of reactive oxygen species. Therefore, curcumin is a good alternative for the treatment of PCM.

This study aimed to evaluate the activity of 2'-hydroxychalcone-loaded in nanoemulsion (NLS + 2'chalc), the cytotoxic effect and toxicity against and using a zebrafish model. Preparation and physical-chemical characterization of nanoemulsion (NLS) and NLS + 2'chalc were performed. MIC and minimum fungicide concentration, cytotoxicity and toxicity were also evaluated in the model. NLS + 2'chalc showed fungicidal activity against spp. without cytotoxicity in MRC5 and HepG2 lines. It also had high selectivity index values and no toxicity in the zebrafish model based on MIC values. NLS + 2'chalc is a potential new alternative treatment for paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is a disease caused by fungi of the genus Paracoccidioides . The disease is responsible for high rates of premature deaths and socioeconomic repercussions. The limitations of antifungal agents against PCM have motivated the search for new compounds. In our ongoing exploration of Cerrado plants as potential sources of new antifungal agents, we selected Copaifera langsdorffii oil (Copaíba resin oil) in order to explore its bioactive potential and test a formulation to increase oil stability and solubilization employing Pluronic F-127 to obtain the nanoemulsion of the oil. We aim at testing both Copaíba resin oil and its nanoemulsion against four species of the Paracoccidioides genus. We performed cytotoxicity test in Balb/C3T3 cells, hemolytic activity and interaction of Copaíba resin oil and Copaíba resin oil nanoemulsion (CopaPlu) with the antifungal agents such as amphotericin B, co-trimoxazole, and itraconazole. Moreover, the Copaíba resin oil was analyzed by mass spectrometry to identify its chemical profile. Eventually, a new methodology to prepare the nanoemulsion is presented. The Copaíba resin oil and CopaPlu nanoemulsion inhibited Paracoccidioides sp. growth efficiently, and no cytotoxicity or hemolytic effect was observed at minimum inhibitory concentration (MIC). When combined with amphotericin B, Copaíba resin oil and its nanoemulsion showed an additive effect with reduction of MIC values. The Copaíba resin oil and CopaPlu nanoemulsion is a promising antifungal agent against Paracoccidioides .

and are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with s and is responsible for the differences in the virulence of isolates of these fungi. Because of the importance of adhesion to the establishment of an infection, this study focused on the preliminary development of a new therapeutic strategy to inhibit adhesion by , thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to the cell wall to inhibit adhesion to host cells and extracellular matrix (ECM) components (laminin, fibronectin, and type I and type IV collagen). This approach allowed us to identify four peptides that inhibited up to 64% of the adhesion of to pneumocytes and inhibited the adhesion to the ECM components by up to 57%. Encouraged by these results, we evaluated the ability of these peptides to protect from infection by treating larvae with the different peptides prior to infection with and observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected with by up to 64% and by up to 60% in those infected with . These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy.

Pulmonary fibrosis (PF) is considered the most important sequela developed in patients suffering from the chronic form of paracoccidioidomycosis (PCM), which leads to the loss of respiratory function in 50% of cases; this residual pulmonary abnormality is present even after antifungal treatment. To date, there is no effective treatment for PF. However, the use of antifungal drugs in combination with other antibiotics or immunomodulatory compounds, as well as biological therapies that include a monoclonal antibody specific to neutrophils, or prophylactic vaccination employing a recombinant antigen of Paracoccidioides brasiliensis that successfully attenuated PF, has been reported. Additionally, mesenchymal stem cell transplantation in combination with antifungal therapy slightly reduced the inflammatory response and profibrotic molecules induced by P. brasiliensis infection. In this review, I report experimental findings from several studies aiming to identify promising therapeutic strategies for treating PF developed in PCM.

Paracoccidioidomycosis (PCM) is an important endemic, systemic disease in Latin America caused by spp. This mycosis has been associated with high morbidity and sequels, and its clinical manifestations depend on the virulence of the infecting strain, the degree and type of immune response, infected tissues, and intrinsic characteristics of the host. The T helper(Th)1 and Th17/Th22 cells are related to resistance and control of infection, and a Th2/Th9 response is associated with disease susceptibility. In this study, we focused on interleukin(IL)-12p35 ( ), IL-18 ( ), and IFN-γ receptor 1 ( ) genetic polymorphisms because their respective roles have been described in human PCM. Real-time PCR was employed to analyze -504 G/T (rs2243115), -607 C/A (rs1946518), and -611 A/G (rs1327474) single nucleotide polymorphisms (SNP). One hundred forty-nine patients with the acute form (AF), multifocal chronic (MC), or unifocal chronic (UC) forms of PCM and 110 non-PCM individuals as a control group were included. In the unconditional logistic regression analysis adjusted by ethnicity and sex, we observed a high risk of the -607 -allele for both AF [ = 0.015; OR = 3.10 (95% CI: 1.24-7.77)] and MC groups [ = 0.023; OR = 2.61 (95% CI: 1.14-5.96)] when compared with UC. The -607 -allele associated risk for the AF and MC groups as well as the protective role of the -allele in UC are possibly linked to higher levels of IL-18 at different periods of the course of the disease. Therefore, a novel role of -607 C/A SNP is shown in the present study, highlighting its importance in the outcome of PCM.

Paracoccidioidomycosis, the most important systemic mycosis in Latin America, is closely linked to rural activities. In Brazil, it is an endemic disease, with an estimated 4,000 to 6,000 annual cases, accounting for over 80% of the global diagnoses. We present an intriguing case of this disease with an intestinal manifestation in a 71-year-old woman. The involvement of the cecal appendix led to a complication of cholangitis that mimicked cholangiocarcinoma.