In this review, we describe the manufacturing process of Japanese soy sauce, the characteristics of koji molds that are suitable for soy sauce brewing, and the key enzymes produced by koji molds and their roles in the degradation of materials during soy sauce fermentation, focusing on the production of umami taste in soy sauce brewing.The existence of a hyperinflammatory state has been observed in patients with invasive fungal infections (IFI). It is being postulated whether morbidity from IFI may, in part, be a consequence of an unnecessarily prolonged or exaggerated proinflammatory immune response including interleukin 6 (IL-6) post-infection, in a host with dysregulated or compromised immunity. This, in turn, induces collateral host injury at the tissue and organ level, leading to adverse outcomes. Tocilizumab has become widely used as an immunomodulator in the treatment of inflammatory conditions. Here, we evaluated the use of tocilizumab to curb post-infective inflammatory flare in the setting of an in-vivo mouse model for invasive candidiasis. Following Candida infection, the tocilizumab-treated mice showed improved short-term survival compared with the saline-treated control mice. There was a reduced inflammatory response mounted by the host, coupled with reduced IL-6 but increased IL-10 levels. TNF-α and IFN-γ responses were not affected. Tocilizumab facilitated immune tolerance by selectively inducing IL-10, producing CD8α+ conventional dendritic cells (DCs) and peripheral T-regulatory cells, over CD11b+ conventional DCs and plasmacytoid DCs. We demonstrate here the sequelae from immunomodulatory manipulation and the basis whereby the use of monoclonal antibodies may be further explored in IFI.Clinical observations have long suggested that women are protected against paracoccidioidomycosis. 17β-estradiol, the main female estrogen, inhibits conidia-to-yeast transformation (C-to-Y), which is required for the infection establishment. However, experiments in murine models have yielded conflicting results, suggesting that C-to-Y inhibition, alone, fails to explain the female-associated protection and that sexual hormones may also act by modulating the host’s immune responses. Therefore, this issue remains unsolved. Strikingly, no studies have compared the severity of paracoccidioidomycosis between men and women. This retrospective case-control study compared 36 women with 72 age-matched men for clinical-demographic, laboratory, and chest imaging findings. Overall, paracoccidioidomycosis in women presented the main features described in the acute/subacute and chronic forms seen in men. Women also showed similar demographic features and clinical-laboratory and imaging severity scores as men. We additionally reviewed 58 paracoccidioidin skin test surveys undertaken by volunteers from endemic areas. Data accumulated from 10.873 tests showed that females and males are infected with similar magnitudes (21.9% vs. 25.2%) and that reactivity steadily increased with age, peaking after the age of 60. We discuss the paradox of similar infection rates but much lower disease prevalence in women, considering the current pathogenetic views of paracoccidioidomycosis, and we raise alternative hypotheses to account for this paradox.Studies of fungal behavior are essential for a better understanding of fungal-driven ecological processes. Here, we evaluated the effects of timing of resource (bait) addition on the behavior of fungal mycelia when it remains in the inoculum and when it migrates from it towards a bait, using cord-forming basidiomycetes. Experiments allowed mycelium to grow from an inoculum wood across the surface of a soil microcosm, where it encountered a new wood bait 14 or 98 d after the start of growth. After the 42-d colonization of the bait, inoculum and bait were individually moved to a dish containing fresh soil to determine whether the mycelia were able to grow out. When the inoculum and bait of mycelia baited after 14 d were transferred to new soil, there was 100% regrowth from both inoculum and bait in Pholiota brunnescens and Phanerochaete velutina, indicating that no migration occurred. However, when mycelium was baited after 98 d, 3 and 4 out of 10 replicates of P. brunnescens and P. velutina, respectively, regrew only from bait and not from inoculum, indicating migration. These results suggest that prolonged periods without new resources alter the behavior of mycelium, probably due to the exhaustion of resources.Human infectious fungal diseases are increasing, despite improved hygienic conditions. We present a case of gastrointestinal basidiobolomycosis (GIB) in a 20-year-old male with a history of progressively worsening abdominal pain. The causative agent was identified as a novel Basidiobolus species. Validation of its novelty was established by analysis of the partial ribosomal operon of two isolates from different organs. Phylogeny of ITS and LSU rRNA showed that these isolates belonged to the genus Basidiobolus, positioned closely to B. heterosporus and B. minor. Morphological and physiological data supported the identity of the species, which was named Basidiobolus omanensis, with CBS 146281 as the holotype. The strains showed high minimum inhibitory concentrations (MICs) to fluconazole (>64 µg/mL), itraconazole and voriconazole (>16 µg/mL), anidulafungin and micafungin (>16 µg/mL), but had a low MIC to amphotericin B (1 µg/mL). The pathogenic role of B. omanensis in gastrointestinal disease is discussed. We highlight the crucial role of molecular identification of these rarely encountered opportunistic fungi.The host lymphocyte response is decisive in Pneumocystis pneumonia (PCP) pathophysiology but little is known of the specific roles of lymphocyte subpopulations in this fungal infection. Peripheral NK, NKT, B, TCD4+ and TCD8+ subpopulations were compared by immunophenotyping between 20 patients diagnosed with PCP (PCP(+)] and 20 uninfected immunosuppressed patients (PCP(-)). Among PCP(+) subjects, the lymphocyte populations were also compared between surviving and deceased patients. Low B cell count ( less then 40 cells/µL) was more frequent in PCP(+) than in PCP(-) patients (p = 0.03), while there was no difference for the TCD4 count. Among the PCP(+) group, the 7 deceased patients had lower Th1 (p = 0.02) and Tc1 (p = 0.03) populations, higher Th2 response (p = 0.03), higher effector TCD8 (p less then 0.01), lower central memory TCD8 (p = 0.04) and reduced NK cells (p = 0.02) compared with the 13 survivors. Th1/Th2 ratio less then 17, CD8 Tc1 less then 44%, effector TCD8 less then 25%, central memory TCD8 less then 4%, NK cells less then 50 cells/µL and total lymphocytes less then 0.75 G/L were associated with a higher risk of mortality (p = 0.003, p = 0.007, p = 0.0007, p = 0.004, p = 0.02 and p = 0.019, respectively). The traditional analysis of TCD4 and TCD8 populations may be insufficient in the context of PCP. It could be completed by using B cells to predict the risk of PCP, and by using lymphocyte subpopulations or total lymphocyte count, which are easy to obtain in all health care facilities, to evaluate PCP prognosis.Fungi associated with macroalgae are less known when compared with those on wood in the marine environment. In this study, we assessed the diversity of fungi associated with the red alga Pterocladiella capillacea at Chao-Jin Park, Keelung, Taiwan. Algal segments of healthy and dead thalli were washed/sterilized with different solutions (sterile artificial seawater, 70% ethanol, and 4% sodium hypochlorite), plated on three different media (glucose-yeast extract-peptone seawater agar (GYPS), potato dextrose seawater agar (PDAS), and artificial seawater agar (SA)), and isolated as pure cultures. Identification was mainly based on BLAST search analysis of the internal transcribed spacers of rDNA (ITS). The highest isolation frequency (no. of segment with fungi/total no. of segment × 100) was in dead thalli (61.23%), thalli washed with seawater (88.38%), and thalli plated on GYPS (62.10%). A total of 3187 isolates were cultured, representing 129 taxa (in 67 genera); the higher species richness was isolated from healthy thalli (119 species), thalli washed with seawater (111 species), and on GYPS (112 species). Ascomycota (Eurotiales, Hypocreales, Capnodiales, Pleosporales, Xylariales) dominated the fungal community in P. capillacea with many basidiomycetous yeasts and few Mucoromycota. Aspergillus, Cladosporium, Penicillium (Ascomycota), and Rhodosporidium (Basidiomycota) were the dominant genera associated with the alga. The surface washing/sterilization schemes of algal thalli affected fungal diversity, but the isolation media used did not. While these genera are known producers of antimicrobial secondary metabolites, they might form a mutualistic relationship with P. capillacea by exchanging nutrients from photosynthesis for protection from microbial diseases.In view of the ever-growing human population and global environmental crisis, new technologies are emerging in all fields of our life. In the last two decades, the development of cold plasma (CP) technology has offered a promising and environmentally friendly solution for addressing global food security problems. Besides many positive effects, such as promoting seed germination, plant growth, and development, CP can also serve as a surface sterilizing agent. It can be considered a method for decontamination of microorganisms on the seed surface alternative to the traditional use of fungicides. This review covers basics of CP technology and its application in seed decontamination. As this is a relatively young field of research, the data are scarce and hard to compare due to various plasma setups and parameters. On the other hand, the rapidly growing research field offers opportunities for novel findings and applications.Candida auris is a multidrug-resistant, difficult-to-eradicate pathogen that can colonize patients and health-care environments and cause severe infections and nosocomial outbreaks, especially in intensive care units. We observed an extremely low-birth-weight (800 g), preterm neonate born from vaginal delivery from a C. auris colonized mother, who was colonized by C. auris within a few hours after birth. We could not discriminate whether the colonization route was the birth canal or the intensive care unit environment. The infant died on her third day of life because of complications related to prematurity, without signs or symptoms of infections. In contexts with high rates of C.auris colonization, antifungal prophylaxis in low-birth-weight, preterm neonates with micafungin should be considered over fluconazole due to the C. auris resistance profile, at least until its presence is excluded.This review brings together the research efforts on salt marsh fungi, including their geographical distribution and host association. A total of 486 taxa associated with different hosts in salt marsh ecosystems are listed in this review. The taxa belong to three phyla wherein Ascomycota dominates the taxa from salt marsh ecosystems accounting for 95.27% (463 taxa). The Basidiomycota and Mucoromycota constitute 19 taxa and four taxa, respectively. Dothideomycetes has the highest number of taxa, which comprises 47.12% (229 taxa), followed by Sordariomycetes with 167 taxa (34.36%). Pleosporales is the largest order with 178 taxa recorded. Twenty-seven genera under 11 families of halophytes were reviewed for its fungal associates. Juncus roemerianus has been extensively studied for its associates with 162 documented taxa followed by Phragmites australis (137 taxa) and Spartina alterniflora (79 taxa). The highest number of salt marsh fungi have been recorded from Atlantic Ocean countries wherein the USA had the highest number of species recorded (232 taxa) followed by the UK (101 taxa), the Netherlands (74 taxa), and Argentina (51 taxa). China had the highest number of salt marsh fungi in the Pacific Ocean with 165 taxa reported, while in the Indian Ocean, India reported the highest taxa (16 taxa). Many salt marsh areas remain unexplored, especially those habitats in the Indian and Pacific Oceans areas that are hotspots of biodiversity and novel fungal taxa based on the exploration of various habitats.Azoles are one of the most widely used drugs to treat fungal infections. To further understand the fungal response to azoles, we analyzed the MAPK circuitry of the model yeast Saccharomyces cerevisiae that operates under treatment with these antifungals. Imidazoles, and particularly clotrimazole, trigger deeper changes in MAPK phosphorylation than triazoles, involving a reduction in signaling through the mating pathway and the activation of the MAPKs Hog1 and Slt2 from the High-Osmolarity Glycerol (HOG) and the Cell Wall Integrity (CWI) pathways, respectively. Clotrimazole treatment leads to actin aggregation, mitochondrial alteration, and oxidative stress, which is essential not only for the activation of both MAPKs, but also for the appearance of a low-mobility form of Slt2 caused by additional phosphorylation to that occurring at the conserved TEY activation motif. Clotrimazole-induced ROS production and Slt2 phosphorylation are linked to Tpk3-mediated PKA activity. Resistance to clotrimazole depends on HOG and CWI-pathway-mediated stress responses. However, Pkc1 and other proteins acting upstream in the pathway are not critical for the activation of the Slt2 MAPK module, suggesting a novel rewiring of signaling through the CWI pathway. We further show that the strong impact of azole treatment on MAPK signaling is conserved in other yeast species.The effective management of Fusarium wilt of bananas (FWB) depends on the knowledge of the disease dynamics in time and space. The objectives of this work were to estimate disease intensity and impact, and to investigate the spatial and temporal dynamics of FWB. Fields planted with Silk (n = 10), Pome (n = 17), or Cavendish (n = 3) banana subgroups were surveyed in Brazil, totaling 95 ha. In each field, all plants were visually assessed, and diseased plants were georeferenced. The incidence of FWB and the impact of the disease on the yield on a regional scale were estimated. Spatial patterns were analyzed using quadrat- and distance-based methods. FWB incidence ranged from 0.09% to 41.42%, being higher in Silk fields (median = 14.26%). Impacts of epidemics on yield ranged from 18.4 to 8192.5 kg ha-1 year-1, with an average of 1856.7 kg ha-1 year-1. The higher economic impact of the disease was observed on Silk cultivar with an average loss of USD 1974.2 ha-1 year-1. Overall, estimated losses increased on average by USD 109.8 ha-1 year-1 at each 1% of incidence. Aggregation of FWB was detected by all analytical methods in 13 fields (1 of Cavendish, 11 of Pome, and 1 of Silk). In the other 17 fields, at least one analytical method did not reject the null hypothesis of randomness. One field (5 ha), composed of six plots, was selected for spatial and temporal studies during two years with bi-monthly assessments. A sigmoidal curve represented the FWB progress and the Gompertz model best-fitted disease progress. The level of aggregation varied over time, and evidence of secondary infection to neighboring and distant plants was detected. FWB is a widespread problem in Brazil and yield losses can be of high magnitude. Epidemiology-based management strategies can now be better established.In this study, we investigated aqueous extracts of three edible mushrooms Agaricus bisporus (white button mushroom), Pleurotus columbinus (oyster mushroom), and Pleurotus sajor-caju (grey oyster mushroom). The extracts were biochemically characterized for total carbohydrate, phenolic, flavonoid, vitamin, and protein contents besides amino acid analysis. Triple TOF proteome analysis showed 30.1% similarity between proteomes of the two Pleurotus spp. All three extracts showed promising antiviral activities. While Pleurotus columbinus extract showed potent activity against adenovirus (Ad7, selectivity index (SI) = 4.2), Agaricus bisporus showed strong activity against herpes simplex II (HSV-2; SI = 3.7). The extracts showed low cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs) and moderate cytotoxicity against prostate (PC3, DU-145); colorectal (Colo-205); cecum carcinoma (LS-513); liver carcinoma (HepG2); cervical cancer (HeLa); breast adenocarcinoma (MDA-MB-231 and MCF-7) as well as leukemia (CCRF-CEM); acute monocytic leukemia (THP1); acute promyelocytic leukemia (NB4); and lymphoma (U937) cell lines. Antioxidant activity was evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging, 2,2′-Azinobis-(3-Ethylbenzthiazolin-6-Sulfonic Acid) ABTS radical cation scavenging, and oxygen radical absorbance capacity (ORAC) assays. The three extracts showed potential antioxidant activities with the maximum activity recorded for Pleurotus columbinus (IC50 µg/mL) = 35.13 ± 3.27 for DPPH, 13.97 ± 4.91 for ABTS, and 29.42 ± 3.21 for ORAC assays.The recent introduction of the chytrid fungus Batrachochytrium salamandrivorans into northeastern Spain threatens salamander diversity on the Iberian Peninsula. We assessed the current epidemiological situation with extensive field sampling of urodele populations. We then sought to delineate priority regions and identify conservation units for the Iberian Peninsula by estimating the susceptibility of Iberian urodeles using laboratory experiments, evidence from mortality events in nature and captivity and inference from phylogeny. None of the 1395 field samples, collected between 2015 and 2021 were positive for Bsal and no Bsal-associated mortality events were recorded, in contrast to the confirmed occurrence of Bsal outbreak previously described in 2018. We classified five of eleven Iberian urodele species as highly susceptible, predicting elevated mortality and population declines following potential Bsal emergence in the wild, five species as intermediately susceptible with variable disease outcomes and one species as resistant to disease and mortality. We identified the six conservation units (i.e., species or lineages within species) at highest risk and propose priority areas for active disease surveillance and field biosecurity measures. The magnitude of the disease threat identified here emphasizes the need for region-tailored disease abatement plans that couple active disease surveillance to rapid and drastic actions.The ability of Trichoderma reesei, a fungus widely used for the commercial production of hemicellulases and cellulases, to grow and modify technical soda lignin was investigated. By quantifying fungal genomic DNA, T. reesei showed growth and sporulation in solid and liquid cultures containing lignin alone. The analysis of released soluble lignin and residual insoluble lignin was indicative of enzymatic oxidative conversion of phenolic lignin side chains and the modification of lignin structure by cleaving the β-O-4 linkages. The results also showed that polymerization reactions were taking place. A proteomic analysis conducted to investigate secreted proteins at days 3, 7, and 14 of growth revealed the presence of five auxiliary activity (AA) enzymes in the secretome AA6, AA9, two AA3 enzymes), and the only copper radical oxidase encoded in the genome of T. reesei. This enzyme was heterologously produced and characterized, and its activity on lignin-derived molecules was investigated. Phylogenetic characterization demonstrated that this enzyme belonged to the AA5_1 family, which includes characterized glyoxal oxidases. However, the enzyme displayed overlapping physicochemical and catalytic properties across the AA5 family. The enzyme was remarkably stable at high pH and oxidized both, alcohols and aldehydes with preference to the alcohol group. It was also active on lignin-derived phenolic molecules as well as simple carbohydrates. HPSEC and LC-MS analyses on the reactions of the produced protein on lignin dimers (SS ββ, SS βO4 and GG β5) uncovered the polymerizing activity of this enzyme, which was accordingly named lignin copper oxidase (TrLOx). Polymers of up 10 units were formed by hydroxy group oxidation and radical formation. The activations of lignin molecules by TrLOx along with the co-secretion of this enzyme with reductases and FAD flavoproteins oxidoreductases during growth on lignin suggest a synergistic mechanism for lignin breakdown.Csn5 is a subunit ofthe COP9/signalosome complex in model fungi. Here, we report heavier accumulation of orthologous Csn5 in the nucleus than in the cytoplasm and its indispensability to insect pathogenicity and virulence-related cellular events of Beauveria bassiana. Deletion of csn5 led to a 68% increase in intracellular ubiquitin accumulation and the dysregulation of 18 genes encoding ubiquitin-activating (E1), -conjugating (E2), and -ligating (E3) enzymes and ubiquitin-specific proteases, suggesting the role of Csn5 in balanced ubiquitination/deubiquitination. Consequently, the deletion mutant displayed abolished insect pathogenicity, marked reductions in conidial hydrophobicity and adherence to the insect cuticle, the abolished secretion of cuticle penetration-required enzymes, blocked haemocoel colonisation, and reduced conidiation capacity despite unaffected biomass accumulation. These phenotypes correlated well with sharply repressed or abolished expressions of key hydrophobin genes required for hydrophobin biosynthesis/assembly and of developmental activator genes essential for aerial conidiation and submerged blastospore production. In the mutant, increased sensitivities to heat shock and oxidative stress also correlated with reduced expression levels of several heat-responsive genes and decreased activities of antioxidant enzymes. Altogether, Csn5-reliant ubiquitination/deubiquitination balance coordinates the expression of those crucial genes and the quality control of functionally important enzymes, which are collectively essential for fungal pathogenicity, virulence-related cellular events, and asexual development.Mucormycosis is caused by fungi belonging to the order Mucorales. The term „Black Fungus” has been widely applied to human pathogenic Mucorales in India. They mainly infect the sinuses and brain, lungs, stomach and intestines, and skin. While this has been considered a rare disease, thousands of cases have been reported during the second wave of COVID-19 in India, between the months of April and June 2021. Hitherto, more than 45,374 cases and over 4300 deaths have been reported among COVID-19 patients across India from April 2021 to July 21, 2021. Though the mortality rate is estimated to be 50%, it could be above 90% if left untreated. In India, Rhizopus arrhizus has been related to be the most common species to cause human mucormycosis, followed by Apophysomyces variabilis, Rhizopus microsporus, and R. homothallicus. Accurate sample identification of human pathogenic Mucorales species is challenging especially due to the frequent lack of diagnostic morphological features. Traditionally, the culture-based apIndia and neighboring countries.The present study was designed to explore the effects of the endophyte Epichloë gansuensis on gene expression related to plant hormone biosynthesis and response pathways and the content of salicylic acid (SA) and jasmonic acid (JA) hormones of Achnatherum inebrians, under different moisture conditions. Through a pot experiment and transcriptome analysis, we found a total of 51 differentially expressed genes (DEGs) related to hormone biosynthesis and response pathways, including 12 auxin related genes, 8 cytokinin (CTK) related genes, 3 gibberellin (GA) related genes, 7 abscisic acid (ABA) related genes, 7 ethylene (ET) related genes, 12 JA related genes and 4 SA related genes. Furthermore, key genes of JA and SA biosynthesis and response pathways, such as LOX2S, AOS, OPR, ACX, JMT, JAZ, PAL, NPR1, TGA and PR-1, showed different degrees of upregulation or downregulation. Under 60% soil moisture content, the JA content of endophyte-free (EF) A. inebrians was significantly (p less then 0.05) higher than that of endophyte-infected (EI) A. inebrians. Under 30% and 60% soil moisture content, the SA content of EF A. inebrians was significantly (p less then 0.05) higher than that of EI A. inebrians. SA content of EI A. inebrians under 30% and 60% soil moisture content was significantly (p less then 0.05) higher than that under 15% soil moisture content. With both EI and EF plants, the SA and JA levels, respectively, are very similar at 15% soil moisture content. This study has revealed that E. gansuensis differentially activated plant hormone synthesis and signal transduction pathways of A. inebrians plants under different soil moisture availability.(1) Background Lung transplant recipients (LTRs) are at substantial risk of invasive fungal disease (IFD), although no consensus has been reached on the use of antifungal agents (AFAs) after lung transplantation (LTx). This study aimed to assess the risk factors and prognosis of fungal infection after LTx in a single tertiary center in South Korea. (2) Methods The study population included all patients who underwent LTx between January 2012 and July 2019 at a tertiary hospital. It was a retrospective cohort study. Culture, bronchoscopy, and laboratory findings were reviewed during episodes of infection. (3) Results Fungus-positive respiratory samples were predominant in the first 90 days and the overall cumulative incidence of Candida spp. was approximately three times higher than that of Aspergillus spp. In the setting of itraconazole administration for 6 months post-LTx, C. glabrata accounted for 36.5% of all Candida-positive respiratory samples. Underlying connective tissue disease-associated interstitial lung disease, use of AFAs before LTx, a longer length of hospital stay after LTx, and old age were associated with developing a fungal infection after LTx. IFD and fungal infection treatment failure significantly increased overall mortality. Host factors, antifungal drug resistance, and misdiagnosis of non-Aspergillus molds could attribute to the breakthrough fungal infections. (4) Conclusions Careful bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are recommended during the first year after LTx.Aspergillus oryzae is a filamentous fungus that has been used in traditional Japanese brewing industries, such as the sake, soy sauce, and miso production. In addition, A. oryzae has been used in heterologous protein production, and the fungus has been recently used in biosynthetic research due to its ability to produce a large amount of heterologous natural products by introducing foreign biosynthetic genes. Genetic manipulation, which is important in the functional development of A. oryzae, has mostly been limited to the wild strain RIB40, a genome reference suitable for laboratory analysis. However, there are numerous industrial brewing strains of A. oryzae with various specialized characteristics, and they are used selectively according to the properties required for various purposes such as sake, soy sauce, and miso production. Since the early 2000s, genome editing technologies have been developed; among these technologies, transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) have been applied to gene modification in A. oryzae. Notably, the CRISPR/Cas9 system has dramatically improved the efficiency of gene modification in industrial strains of A. oryzae. In this review, the development of genome editing technology and its application potentials in A. oryzae are summarized.The objective of this study was to assess the comparative efficacy and safety of different antifungal agents used for the treatment of oropharyngeal candidiasis (OPC) in adult patients with HIV. A systematic search was performed on the four major databases (Medline, Embase, CENTRAL and Scopus) to identify randomized controlled trials (RCTs) that evaluated the efficacy of antifungal agents in HIV patients with OPC. A network meta-analysis was performed from the data extracted from the selected studies. The agents were ranked according using surface under the cumulative ranking (SUCRA). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of evidence. A total of 15 trials were included in the quantitative analysis involving the data from a total of 2883 participants. Fluconazole was ranked as the most effective antifungal agent to achieve clinical cure (SUCRA = 0.87) in OPC followed by posaconazole and itraconazole. Posaconazole was ranked the most efficacious agent in achieving mycological cure (SUCRA = 0.81), followed by fluconazole. While nystatin was ranked the safest, the effect estimates of none of the other systemic antifungal agents were significantly higher than fluconazole. Based on the available evidence, fluconazole can be considered as the most effective drug in the treatment of OPC among HIV-infected adults and has a favorable safety profile, followed by posaconazole.Next-generation sequencing (NGS) technologies have recently developed beyond the research realm and started to mature into clinical applications. Here, we review the current use of NGS for laboratory diagnosis of fungal infections. Since the first reported case in 2014, >300 cases of fungal infections diagnosed by NGS were described. Pneumocystis jirovecii is the predominant fungus reported, constituting ~25% of the fungi detected. In ~12.5% of the cases, more than one fungus was detected by NGS. For P. jirovecii infections diagnosed by NGS, all 91 patients suffered from pneumonia and only 1 was HIV-positive. This is very different from the general epidemiology of P. jirovecii infections, of which HIV infection is the most important risk factor. The epidemiology of Talaromyces marneffei infection diagnosed by NGS is also different from its general epidemiology, in that only 3/11 patients were HIV-positive. The major advantage of using NGS for laboratory diagnosis is that it can pick up all pathogens, particularly when initial microbiological investigations are unfruitful. When the cost of NGS is further reduced, expertise more widely available and other obstacles overcome, NGS would be a useful tool for laboratory diagnosis of fungal infections, particularly for difficult-to-grow fungi and cases with low fungal loads.Grains and cassava-based foods serve as major dietary sources for many households in Nigeria. However, these foods are highly prone to contamination by moulds and aflatoxins owing to poor storage and vending practices. Therefore, we studied the fungal diversity in maize, cassava-based flour (pupuru), and rice vended in markets from Ondo state, Nigeria, and assessed their aflatoxin levels using an enzyme-linked immunosorbent assay. Molecular analysis of 65 representative fungal isolates recovered from the ground grains and pupuru samples revealed 26 species belonging to five genera Aspergillus (80.9%), Penicillium (15.4%), and Talaromyces (1.9%) in the Ascomycota; Syncephalastrum (1.2%) and Lichtheimia (0.6%) in Mucoromycota. Aspergillus flavus was the predominant species in the ground grains and pupuru samples. Aflatoxins were found in 73.8% of the 42 representative food samples and 41.9% exceeded the 10 μg/kg threshold adopted in Nigeria for total aflatoxins.Diplodia sapinea is a cosmopolitan endophyte and opportunistic pathogen having occurred on several conifer species in Europe for at least 200 years. In Europe, disease outbreaks have increased on several Pinus spp. in the last few decades. In this study, the genetic structure of the European and western Asian D. sapinea population were investigated using 13 microsatellite markers. In total, 425 isolates from 15 countries were analysed. A high clonal fraction and low genetic distance between most subpopulations was found. One single haplotype dominates the European population, being represented by 45.3% of all isolates and found in nearly all investigated countries. Three genetically distinct subpopulations were found Central/North European, Italian and Georgian. The recently detected subpopulations of D. sapinea in northern Europe (Estonia) share several haplotypes with the German subpopulation. The northern European subpopulations (Latvia, Estonia and Finland) show relatively high genetic diversity compared to those in central Europe suggesting either that the fungus has existed in the North in an asymptomatic/endophytic mode for a long time or that it has spread recently by multiple introductions. Considerable genetic diversity was found even among isolates of a single tree as 16 isolates from a single tree resulted in lower clonal fraction index than most subpopulations in Europe, which might reflect cryptic sexual proliferation. According to currently published allelic patterns, D. sapinea most likely originates from North America or from some unsampled population in Asia or central America. In order to enable the detection of endophytic or latent infections of planting stock by D. sapinea, new species-specific PCR primers (DiSapi-F and Diplo-R) were designed. During the search for Diplodia isolates across the world for species specific primer development, we identified D. africana in California, USA, and in the Canary Islands, which are the first records of this species in North America and in Spain.The study of the contribution of the plant defence hormones, salicylic acid (SA) and jasmonic acid (JA), in the resistance against pathogens of plants associated with Epichloë fungal endophytes has been scanty. We hypothesised that Epichloë spp., capable of inducing host plant SA-dependent defences, would increase the levels of plant resistance against biotrophic pathogens. Plants of Achnatherum inebrians, with and without the fungal endophyte Epichloë gansuensis, were inoculated with the biotrophic fungal pathogen Blumeria graminis. We measured the status of plant defences (associated with SA and JA signalling pathways) and the levels of resistance to the pathogen. Plants associated with the endophyte showed less disease symptoms caused by the biotrophic pathogen than plants without the endophyte. In agreement with our hypothesis, the Epichloë endophyte increased the plant production of SA and enhanced the expression levels of plant genes of synthesis and response to the SA hormone. The elevated expression of SA-related genes coding for putative plant enzymes with anti-fungal activities promoted by the endophyte may explain the enhanced resistance to the pathogen. The present study highlights that interaction between the plant immune system and Epichloë fungal endophytes can contribute significantly to the resistance of endophyte-symbiotic plants against pathogens.The present study was carried out to analyze the potential of fungi isolated from the rhizosphere of soybean, brinjal, tomato, and potato plants. The density of fungi varied in the pot soil and rhizosphere after Paecilomyces formosus MD12 treatment. The P. formosus MD12 population was 6.3 ± 0.13 × 104 CFU g-1 in the pot planted with brinjal, and the population increased in the rhizosphere (6.72 ± 0.41 × 104 CFU g-1). P. formosus MD12 was cultured in the production medium, and the supernatant was used for egg inhibition studies on a root-knot nematode parasite, Meloidogyne incognita. It was revealed that maximum egg inhibition (94.7 ± 6.2%) was obtained at 100% concentration of extract. The culture supernatant from P. formosus MD12 affected the development of M. incognita juvenile, and the mortality rate was maximum after 96 h (95 ± 6%). Mortality was reduced when treated with 25%, 50%, and 75% supernatant. At 1 × 107 mL-1 of spore suspension, we found reductions of 71.6 ± 3.3% nematode populations in the soil, 60.7 ± 2.2% from the root, and 63.6 ± 2.4% egg mass compared with the control in the pot experiment. The culture supernatant applied at the 10% level showed a maximum mean reduction of the nematode population in roots (72.4 ± 2.2%), soil (77.9 ± 2.5%), and egg masses (73.2 ± 1.5%), respectively. The presence of P. formosus MD12 in a soil environment could antagonize nematode parasites and improve soil amendment. The P. formosus MD12 strain showed good biocontrol ability against the root-knot nematode, M. incognita, under in vitro and green house experimental condition.Prevalence of allergy to fungi is around 3-10%. The most prevalent species involved in sensitizations are Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, and Penicillium notatum. Our main objective was to estimate the prevalence of fungal sensitization and its variation across Spain. Following the ICH-GCP, we recruited 1156 patients from 15 allergy departments in Spain. Hospitals were selected by bioclimatic areas. Patients underwent a skin prick test (SPT) with fungi, pollens, house dust mites, and animal dander. Specific IgE to Alternaria alternata and Alt a 1 was assessed in patients with positive SPT to fungi. Of the 233 patients (20.2%) sensitized to at least one of the five fungi tested, 162 (69.5%) were sensitized to Alternaria alternata and Alt a 1, of whom 113 (69.8%) were children; 181 (77.7%) were also polysensitized to other allergens. Alternaria alternata and Alt a 1 sensitization was present in 25.4% of patients in the Continental area, 12.0% in the Mediterranean area, 7.0% in the Semidesertic area, and 2.3% in the Oceanic area. Prevalence of sensitization to the other tested sources was 63.8% to pollens, 60.5% to house dust mite, and 38.1% to animal dander. We concluded that the prevalence of fungal allergy is increasing. Fungi are still the fourth source of allergen sensitization. Alternaria alternata sensitization is the most prevalent in allergic patients to fungi. Alt a 1 is present in almost 90% of the patients sensitized to Alternaria alternata.Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii. The host immune responses that define disease outcome during infection are largely unknown, although T helper responses are required. Adaptive immunity is influenced by innate immunity as antigen-presenting cells activate and educate adaptive responses. Macrophage and dendritic cell (DC) recognition of pathogen surface molecules are critical for Coccidioides clearance. We characterize the broad innate immune responses to Coccidioides by analyzing macrophage and dendritic cell responses to Coccidioides arthroconidia using avirulent, vaccine Coccidioides strain NR-166 (Δcts2/Δard1/Δcts3), developed from parental virulent strain C735. We developed a novel flow cytometry-based method to analyze macrophage phagocytosis to complement traditional image-scoring methods. Our study found that macrophage polarization is blocked at M0 phase and activation reduced, while DCs polarize into proinflammatory DC1s, but not anti-inflammatory DC2, following interaction with Coccidioides. However, DCs exhibit a contact-dependent reduced activation to Coccidioides as defined by co-expression of MHC-II and CD86. In vivo, only modest DC1/DC2 recruitment and activation was observed with avirulent Coccidioides infection. In conclusion, the vaccine Coccidioides strain recruited a mixed DC population in vivo, while in vitro data suggest active innate immune cell inhibition by Coccidioides.The burden of fungal infections is not widely appreciated. Although these infections are responsible for over one million deaths annually, it is estimated that one billion people are affected by severe fungal diseases. Mycoses of nails and skin, primarily caused by fungi known as dermatophytes, are the most common fungal infections. Trichophyton rubrum appears to be the most common causative agent of dermatophytosis, followed by Trichophyton interdigitale. An estimated 25% of the world’s population suffers from dermatomycosis. Although these infections are not lethal, they compromise the quality of life of infected patients. The outcome of antidermatophytic treatments is impaired by various conditions, such as resistance and tolerance of certain dermatophyte strains. The adage „know your enemy” must be the focus of fungal research. There is an urgent need to increase awareness about the significance of these infections with precise epidemiological data and to improve knowledge regarding fungal biology and pathogenesis, with an emphasis on adaptive mechanisms to tackle adverse conditions from host counteractions. This review outlines the current knowledge about dermatophyte infections, with a focus on signaling pathways required for fungal infection establishment and a broad perspective on cellular and molecular factors involved in antifungal resistance and tolerance.This study led to the discovery of three entomopathogenic fungi associated with Kuwanaspis howardi, a scale insect on Phyllostachys heteroclada (fishscale bamboo) and Pleioblastus amarus (bitter bamboo) in China. Two of these species belong to Podonectria P. kuwanaspidis X.L. Xu & C.L. Yang sp. nov. and P. novae-zelandiae Dingley. The new species P. kuwanaspidis has wider and thicker setae, longer and wider asci, longer ascospores, and more septa as compared with similar Podonectria species. The morphs of extant species P. novae-zelandiae is confirmed based on sexual and asexual morphologies. Maximum likelihood and Bayesian inference analyses of ITS, LSU, SSU, tef1-α, and rpb2 sequence data provide further evidence for the validity of the two species and their placement in Podonectriaceae (Pleosporales). The second new species, Microcera kuwanaspidis X.L. Xu & C.L. Yang sp. nov., is established based on DNA sequence data from ITS, LSU, SSU, tef1-α, rpb1, rpb2, acl1, act, cmdA, and his3 gene regions, and it is characterized by morphological differences in septum numbers and single conidial mass.Fusarium oxysporum f.sp. cubense, causal agent of Panama disease, is one of the biggest threats to global banana production, particularly the Cavendish competent tropical race 4 (Foc TR4). It continues to spread globally with detections occurring in regions of the Middle East and new continents such as Africa and South America in the last decade. As the search was on for new management strategies and resistant cultivars to combat the disease, a banana cultivar-screening trial took place in the Northern Territory of Australia, which examined the responses of 24 banana cultivars to the soil borne fungus. These cultivars included material from TBRI, FHIA and selections from Thailand, Indonesia and Australia and evaluated for their resistance to tropical race 4 for two cropping cycles. Several cultivars displayed considerable resistance to Foc TR4, including several FHIA parental lines and hybrids, the Cavendish (AAA) selections GCTCV 215 and GCTCV 247 from TBRI and an Indonesian selection CJ19 showed either very little to no plant death due to the disease.Inorganic polyphosphate (polyP) which is ubiquitously present in both prokaryotic and eukaryotic cells, consists of up to hundreds of orthophosphate residues linked by phosphoanhydride bonds. The biological role of this polymer is manifold and diverse and in fungi ranges from cell cycle control, phosphate homeostasis and virulence to post-translational protein modification. Control of polyP metabolism has been studied extensively in the budding yeast Saccharomyces cerevisiae. In this yeast, a specific class of inositol pyrophosphates (IPPs), named IP7, made by the IP6K family member Kcs1 regulate polyP synthesis by associating with the SPX domains of the vacuolar transporter chaperone (VTC) complex. To assess if this type of regulation was evolutionarily conserved, we determined the elements regulating polyP generation in the distantly related fission yeast Schizosaccharomyces pombe. Here, the VTC machinery is also essential for polyP generation. However, and in contrast to S. cerevisiae, a different IPP class generated by the bifunctional PPIP5K family member Asp1 control polyP metabolism. The analysis of Asp1 variant S. pombe strains revealed that cellular polyP levels directly correlate with Asp1-made IP8 levels, demonstrating a dose-dependent regulation. Thus, while the mechanism of polyP synthesis in yeasts is conserved, the IPP player regulating polyP metabolism is diverse.The host immune response is critical in Pneumocystis pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of Pneumocystis infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.Reactive oxygen species (ROS) regulate several aspects of cell physiology in filamentous fungi including the antioxidant response and development. However, little is known about the signaling pathways involved in these processes. Here, we report Aspergillus nidulans global phosphoproteome during mycelial growth and show that under these conditions, H2O2 induces major changes in protein phosphorylation. Among the 1964 phosphoproteins we identified, H2O2 induced the phosphorylation of 131 proteins at one or more sites as well as the dephosphorylation of a larger set of proteins. A detailed analysis of these phosphoproteins shows that H2O2 affected the phosphorylation of critical regulatory nodes of phosphoinositide, MAPK, and TOR signaling as well as the phosphorylation of multiple proteins involved in the regulation of gene expression, primary and secondary metabolism, and development. Our results provide a novel and extensive protein phosphorylation landscape in A. nidulans, indicating that H2O2 induces a shift in general metabolism from anabolic to catabolic, and the activation of multiple stress survival pathways. Our results expand the significance of H2O2 in eukaryotic cell signaling.Onychomycosis is one of the most frequent reasons for visiting podiatrist clinics. Complementary tests and the accurate identification of the infectious agents are key issues for a successful treatment of onychomycosis. This is particularly important when lifestyle, age and immunodepressed patients increase the prevalence of non-dermatophyte fungal infection. In this paper, we describe issues related to onychomycosis prevalence in a population of patients, mostly with rural lifestyles, visiting a podiatry clinic in a rural area of Spain. A total of 51 cases were studied with an average age of 65.96 ± 21.28 years (the youngest being 16 years and the oldest being 95 years). Fungal agents were isolated using conventional sampling and microbiological culture techniques. The results obtained with these techniques were compared with the results obtained with a direct methodology using molecular biology, by PCR and nucleotide sequencing of the ITS-5.8S rDNA fragment. The classical culture methodology confirmed the infection in 76.5% of the samples (n = 39), while the PCR confirmed the infection in 84.3% (n = 51) of the nails, although the difference between these results did not show statistical significance (p = 0.388). We found a high variability in agents, with more yeasts than dermatophytes as etiological agents of onychomycosis. However, only among individuals older than 65 years, was the difference between yeasts (82%) and dermatophytes (18%) was statistically significant (p = 0.004). Among the agents of non-dermatophyte onychomycosis, we found predominantly fungi (yeasts) of the Candida genus, interestingly with no isolates of Candida albicans, and moulds of the Aspergillus genus.Twenty-three wheat genotypes were evaluated for stripe and leaf rusts, caused by Puccinia striiformis f. sp. tritici and Puccinia triticina f. sp. tritici, respectively, at seedling and adult stages under greenhouses and field conditions during the 2019/2020 and 2020/2021 growing seasons. The race analysis revealed that 250E254 and TTTST races for stripe and leaf rusts, respectively were the most aggressive. Eight wheat genotypes (Misr-3, Misr-4, Giza-171, Gemmeiza-12, Lr34/Yr18, Lr37/Yr17, Lr46/Yr29, and Lr67/Yr46) were resistant to stripe and leaf rusts at seedling and adult stages. This result was confirmed by identifying the resistance genes Lr34/Yr18, Lr37/Yr17, Lr46/Yr29, and Lr67/Yr46 in these genotypes showing their role in the resistance. Sids-14 and Shandweel-1 genotypes were susceptible to stripe and leaf rusts. Twelve crosses between the two new susceptible wheat genotypes and the three slow rusting genes (Lr34/Yr18, Lr37/Yr17, and Lr67/Yr46) were conducted. The frequency distribution of disease severity (%) in F2 plants of the twelve crosses was ranged from 0 to 80%. Resistant F2 plants were selected and the resistance genes were detected. This study is important for introducing new active resistance genes into the breeding programs and preserving diversity among recently released wheat genotypes.A 56-year-old Hispanic man with a history of disseminated coccidioidomycosis was diagnosed with persistent glucocorticoid insufficiency and pseudohyperaldosteronism secondary to posaconazole toxicity. This case was notable for unexpected laboratory findings of both pseudohyperaldosteronism and severe glucocorticoid deficiency due to posaconazole’s mechanism of action on the adrenal steroid synthesis pathway. Transitioning to fluconazole and starting hydrocortisone resolved the hypokalemia but not his glucocorticoid deficiency. This case highlights the importance of recognizing iatrogenic glucocorticoid deficiency with azole antifungal agents and potential long term sequalae.