Infections caused by the opportunistic pathogens Scedosporium/Lomentospora are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. Scedosporium/Lomentospora cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, highlighting the poor response by microglial cells against L. prolificans. Moreover, a great number of Scedosporium/Lomentospora antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing. In conclusion, although many advances have been made, many aspects remain to be elucidated and more research is necessary to shed light on the immune response to Scedosporium/Lomentospora.

The most common genetic hereditary disease affecting Caucasians is Cystic Fibrosis (CF), which is caused by autosomal recessive mutations in the CFTR gene. The most serious consequence is the production of a thick and sticky mucus in the respiratory tract, which entraps airborne microorganisms and facilitates colonization, inflammation, and infection. Therefore, the present article compiles the information about the microbiota and, particularly, the inter-kingdom fungal-bacterial interactions in the CF lung, the molecules involved, and the potential effects that these interactions may have on the course of the disease. Among the bacterial compounds, quorum sensing-regulated molecules such as homoserine lactones, phenazines, rhamnolipids, quinolones, and siderophores (pyoverdine and pyochelin) stand out, but volatile organic compounds, maltophilin, and CF-related bacteriophages are also explained. These molecules exhibit diverse antifungal mechanisms, including iron starvation and induction of reactive oxygen and nitrogen species production. The fungal compounds are less studied, but they include cell wall components, siderophores, patulin, and farnesol. Despite the apparent competition between microorganisms, the persistence of significant rates of bacterial-fungal co-colonization in CF suggests that numerous variables influence it. In conclusion, it is crucial to increase scientific and economic efforts to intensify studies on the bacterial-fungal inter-kingdom interactions in the CF lung.

The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.

The detection of Scedosporium/Lomentospora is still based on non-standardized low-sensitivity culture procedures. This fact is particularly worrying in patients with cystic fibrosis (CF), where these fungi are the second most common filamentous fungi isolated, because a poor and delayed diagnosis can worsen the prognosis of the disease. To contribute to the discovery of new diagnostic strategies, a rapid serological dot immunobinding assay (DIA) that allows the detection of serum IgG against Scedosporium/Lomentospora in less than 15 min was developed. A crude protein extract from the conidia and hyphae of Scedosporium boydii was employed as a fungal antigen. The DIA was evaluated using 303 CF serum samples (162 patients) grouped according to the detection of Scedosporium/Lomentospora in the respiratory sample by culture, obtaining a sensitivity and specificity of 90.48% and 79.30%, respectively; positive and negative predictive values of 54.81% and 96.77%, and an efficiency of 81.72%. The clinical factors associated with the results were also studied using a univariate and a multivariate analysis, which showed that Scedosporium/Lomentospora positive sputum, elevated anti-Aspergillus serum IgG and chronic Pseudomonas aeruginosa infection were significantly associated with a positive result in DIA, while Staphylococcus aureus positive sputum showed a negative association. In conclusion, the test developed can offer a complementary, rapid, simple and sensitive method to contribute to the diagnosis of Scedosporium/Lomentospora in patients with CF.

Recent studies have increasingly focused on the role of fungi, including Candida albicans , in carcinogenesis. Since C. albicans is a component of the human microbiota, particularly on the skin, we investigated its effect on the phenotype and signalling pathways of melanoma cells. Assays for migration, adhesion, angiogenesis, and hepatic metastasis showed that C. albicans promotes a more malignant phenotype in melanoma cells. At the transcriptomic level, C. albicans increased the expression of VEGF ( Vegfa ), and genes associated with MAPK and HIF-1 signalling pathways, and with aerobic glycolysis. Further in vitro analysis revealed that TLRs and EphA2 receptors are involved in the recognition of live C. albicans , stimulating VEGF secretion and expression of the AP-1 transcription factor component c-Fos through p38-MAPK and HIF-1α. These pathways also regulate the expression of other AP-1 constituents such as Atf3 , Jun , and Jund . Moreover, p38-MAPK regulates glycolytic genes like Hk2 , Slc2a1 , and Eno2 . In conclusion, C. albicans activates the p38-MAPK/c-Fos/AP-1 and HIF-1/HIF-1α/c-Fos/AP-1 pathways in melanoma cells, promoting a pro-angiogenic environment and metabolic reprogramming. Therefore, this study clarifies the impact of C. albicans on melanoma cells, which can lead to the use of antifungal therapies as complementary to traditional treatments for melanoma.

The difficulty of accurately identifying Candida auris and the high resistance rates presented have increased the concern in the healthcare setting. Due to this, the aim of this study was to analyse the fungal response to oxidative stress. To achieve this goal, gene and protein expression were examined using qPCR and two-dimensional electrophoresis, respectively, peroxiredoxin Tsa1b being discovered to be overexpressed under oxidative stress. Besides, its antigenicity was also confirmed by western blotting. Subsequently, the significance of Tsa1b was next investigated by creating and characterizing the C. auris ΔTSA1B and C. auris ΔTSA1B::TSA1B strains using CRISPR-Cas9. The findings demonstrated that the ΔTSA1B strain was more susceptible to oxidative and cell wall stressors than the wild-type strain, which was consistent with an increase in the cell wall β-glucan amounts when grown in the presence of oxidative stress. Furthermore, the ΔTSA1B strain was also more vulnerable to the presence of dendritic cells and bone marrow-derived macrophages. Finally, in vivo infections performed in Galleria mellonella and mice showed a slower progression of the disease in those animals infected with the mutant strain. In conclusion, the peroxiredoxin Tsa1b has been identified as an important protein for the C. auris response to oxidative stress and as a virulence factor, allowing for a more thorough knowledge of the pathobiology of this yeast. This study points out the potential that this protein may have for the development of new diagnostic and therapeutic approaches. HIGHLIGHTS: Several metabolic proteins are implicated in C. auris response to oxidative stress C. auris response to oxidative stress is influenced by the Tsa1b peroxiredoxin Lack of Tsa1b generates more susceptibility to stresses and an altered cell wall C. auris Tsa1b is involved in the fungal interaction with host immune cells The Tsa1b of C. auris contributes to the progression of the infection in vivo