J. Fungi, Volume 7, Issue 11 (November 2021) – 112 articles

Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. The underlying etiology of infectious endophthalmitis is typically bacterial or fungal. The mechanism of entry into the eye is either exogenous, involving seeding of an infectious source from outside the eye (e.g., trauma or surgical complications), or endogenous, involving transit of an infectious source to the eye via the bloodstream. The most common organism for fungal endophthalmitis is Candida albicans. The most common clinical manifestation of fungal endophthalmitis is vision loss, but other signs of inflammation and infection are frequently present. Fungal endophthalmitis is a clinical diagnosis, which can be supported by vitreous, aqueous, or blood cultures. Treatment involves systemic and intravitreal antifungal medications as well as possible pars plana vitrectomy. In this review, we examine these essential elements of understanding fungal endophthalmitis as a clinically relevant entity, which threatens patients’ vision. Full article

Mucormycosis, a rare but highly fatal infection, is caused by fungi of the order Mucorales. Due to their ubiquitous nature, reduced susceptibility to antifungals, acid tolerance, and ability to infect immunocompromised patients through rapid dissemination, these fungi have been frequently reported to infect the COVID-19 patients. In order to develop strategies to overcome mucormycosis, it is essential to understand and identify novel Mucorales present in the environment. In this study, we report the identification of four novel pathogenic Mucorales using the silkworm (Bombyx mori) model. The strains’ phylogeny was analyzed using the genome sequence of the large subunit ribosomal ribonucleic acid (LSU rRNA) and the internal transcribed spacer (ITS) region, where strains 1-3, 5-3, and S286-1101 claded with Mucor orantomantidis, and strain 827-14 claded with Backusella lamprospora. All the strains had a cold-sensitive phenotype with their inability to grow prominently at 4 °C. Mucor sp. 1-3 and 5-3 were characterized by their filamentous and yeast-like growth under aerobic and anaerobic conditions, respectively. The yeast colonies of Mucor sp. 5-3 had multipolar budding cells often observed with cleaved cell surfaces under a scanning electron microscope. We further found that these strains were able to kill immunocompromised mice suggesting their pathogenicity to mammals. Our study established an invertebrate model-based screening system to identify novel pathogenic Mucorales from the natural environment and provided a clue towards the rapid increase in COVID-19 related mucormycosis. Full article

Mycorrhizal mutualisms are vital for orchids through germination to adulthood. Fungal species diversity and community composition vary across seasons and plant development stages and affect plant survival, adaptation, and community maintenance. Knowledge of the temporal turnover of mycorrhizal fungi (OMF) remains poorly understood in the eco-physiologically diverse orchids (especially in epiphytic orchids), although it is important to understand the function and adaptation of mycorrhizae. Some species of Pleione are epiphytic plants with annual roots and may recruit different fungal partners during their root lifecycle. Based on continuous samplings of Pleione bulbocodioides during a whole root lifecycle, we characterized the fungal temporal dynamics using Illumina sequencing of the ITS2 region. Our data showed that the plants of P. bulbocodioides were quickly colonized by OMF at root emergence and had a constant OMF composition throughout one root lifecycle, although the OMF richness declined with root aging after a peak occurrence during root elongation. In contrast, the richness of root-inhabiting fungal endophytes kept increasing with root aging and more drastic turnovers were found in their species compositions. Our findings of OMF temporal turnover contribute to further understanding of mycorrhizal associations and adaptation of Orchidaceae and will benefit orchid resource conservation and utilization. Full article

Talaromyces minioluteus belongs to the section Trachyspermi, has a worldwide distribution and has been found on various substrates, especially on various (stored) food commodities and indoor environments. This species is phenotypically and phylogenetically closely related to T. chongqingensis and T. minnesotensis. The phylogenetic and morphological analyses of 37 strains previously identified as T. chongqingensis, T. minnesotensis and T. minioluteus revealed that this clade incudes eight species: the accepted species T. chongqingensis, T. minnesotensis and T. minioluteus, the newly proposed species T. calidominioluteus, T. africanus and T. germanicus, and the new combinations T. gaditanus (basionym Penicillium gaditanum) and T. samsonii (basionym Penicillium samsonii). In this study, we give insight of the phylogenetic relationships and provide detailed descriptions of the species belonging to this clade. Macromorphological features, especially colony growth rates, texture and conidial colors on agar media, are important characters for phenotypic differentiation between species. Full article

To promote Agaricus sinodeliciosus var. Chaidam ZJU-TP-08 growth and metabolites accumulation, a novel integrated strategy was developed by adopting high levels of metal ions coupled with light treatment. The results revealed that yellow and blue light could significantly promote biomass and exopolysaccharides production, respectively. Furthermore, the yellow–blue light shift strategy could stimulate exopolysaccharides formation. Ca²⁺ ions coupled with blue light mostly promoted exopolysaccharides production related to oxidative stress, which was 42.00% and 58.26% higher than that of Ca²⁺ ions coupled with the non-light and dark cultivation without Ca²⁺ ions in 5-L bioreactor. RNA-seq was performed to uncover the underlined molecular mechanism regulated by light-induced gene expressions in exopolysaccharides biosynthesis and oxidative stress. The findings of this work provide valuable insights into adopting metal ions coupled with the light-assisted method for the macrofungus submerged fermentation for exopolysaccharides production. Full article

Objective: To assess the effectiveness of three general prognostic models (APACHE II, SAPS II, and SOFA) with serum galactomannan antigen in a clinically suspected invasive aspergillosis (IA) subpopulation admitted to a respiratory medicine ICU and to identify azole-resistant Aspergillus fumigatus (ARAF) cases. Methodology and Results: A total of 235 clinically suspected IA patients were prospectively enrolled and observed 30-day mortality was 29.7%. The three general models showed poor discrimination assessed by area under receiver operating characteristic (ROC) curves (AUCs, <0.7) and good calibration (p = 0.92, 0.14, and 0.13 for APACHE II, SAPS II, and SOFA, respectively), evaluated using Hosmer–Lemeshow goodness-of-fit tests. However, discrimination was significantly better with galactomannan values (AUC, 0.924). In-vitro antifungal testing revealed higher minimum inhibitory concentration (MIC) for 12/34 isolates (35.3%) whereas azole resistance was noted in 40% of Aspergillus fumigatus isolates (6/15) with two hotspot cyp51A mutations, G54R and P216L. Conclusions: Patients diagnosed with putative and probable IA (71.4% and 34.6%, respectively), had high mortality. The general prognostic model APACHE II seemed fairly accurate for this subpopulation. However, the use of local GM cut-offs calculated for mortality, may help the intensivists in prompt initiation or change of therapy for better outcome of patients. In addition, the high MICs highlight the need of antifungal surveillance to know the local resistance rate which might aid in patient treatment. Full article

Consolidated infection control measures imposed by the government and hospitals during COVID-19 pandemic resulted in a sharp decline of respiratory viruses. Based on the issue of whether Pneumocystis jirovecii could be transmitted by airborne and acquired from the environment, we assessed changes in P. jirovecii pneumonia (PCP) cases in a hospital setting before and after COVID-19. We retrospectively collected data of PCP-confirmed inpatients aged ≥18 years (N = 2922) in four university-affiliated hospitals between January 2015 and June 2021. The index and intervention dates were defined as the first time of P. jirovecii diagnosis and January 2020, respectively. We predicted PCP cases for post-COVID-19 and obtained the difference (residuals) between forecasted and observed cases using the autoregressive integrated moving average (ARIMA) and the Bayesian structural time-series (BSTS) models. Overall, the average of observed PCP cases per month in each year were 36.1 and 47.3 for pre- and post-COVID-19, respectively. The estimate for residuals in the ARIMA model was not significantly different in the total PCP-confirmed inpatients (7.4%, p = 0.765). The forecasted PCP cases by the BSTS model were not significantly different from the observed cases in the post-COVID-19 (−0.6%, 95% credible interval; −9.6~9.1%, p = 0.450). The unprecedented strict non-pharmacological interventions did not affect PCP cases. Full article

Late wilt (LWD) is a vascular wilt disease that outbursts late in maize development, usually during or after flowering. The disease causal agent, the soil and seed-borne fungi, Magnaporthiopsis maydis, causes significant economic losses in Egypt, Israel, Spain, Portugal, and India. Since its discovery in the early 1960s in Egypt, the knowledge base of the disease was significantly expanded. This includes basic information on the pathogen and its mode of action, disease symptoms and damages, methods to study and monitor the pathogen, and above all, control strategies to restrain M. maydis and reduce its impact on commercial maize production. Three approaches stand out from the various control methods inspected. First, the traditional use of chemical pesticides was investigated extensively. This approach gained attention when, in 2018–2020, a feasible and economical treatment based on Azoxystrobin (alone or in combination with other fungicides) was proven to be effective even in severe cases of LWD. Second, the growing trend of replacing chemical treatments with eco-friendly biological and other green protocols has become increasingly important in recent years and has already made significant achievements. Last but not least, today’s leading strategy to cope with LWD is to rely on resistant maize genotypes. The past two decades’ introduction of molecular-based diagnostic methods to track and identify the pathogen marked significant progress in this global effort. Still, worldwide research efforts are progressing relatively slowly since the disease is considered exotic and unfamiliar in most parts of the world. The current review summarizes the accumulated knowledge on LWD, its causal agent, and the disease implications. An additional important aspect that will be addressed is a future perspective on risks and knowledge gaps. Full article

Sensing and responding to changes in NaCl concentration in hypersaline environments is vital for cell survival. In this paper, we identified and characterized key components of the high-osmolarity glycerol (HOG) signal transduction pathway, which is crucial in sensing hypersaline conditions in the extremely halotolerant black yeast Hortaea werneckii and in the obligate halophilic fungus Wallemia ichthyophaga. Both organisms were isolated from solar salterns, their predominating ecological niche. The identified components included homologous proteins of both branches involved in sensing high osmolarity (SHO1 and SLN1) and the homologues of mitogen-activated protein kinase module (MAPKKK Ste11, MAPKK Pbs2, and MAPK Hog1). Functional complementation of the identified gene products in S. cerevisiae mutant strains revealed some of their functions. Structural protein analysis demonstrated important structural differences in the HOG pathway components between halotolerant/halophilic fungi isolated from solar salterns, salt-sensitive S. cerevisiae, the extremely salt-tolerant H. werneckii, and halophilic W. ichthyophaga. Known and novel gene targets of MAP kinase Hog1 were uncovered particularly in halotolerant H. werneckii. Molecular studies of many salt-responsive proteins confirm unique and novel mechanisms of adaptation to changes in salt concentration. Full article

This scoping review is aimed at the application of the metabolomics platform to dissect key metabolites and their intermediates to observe the regulatory mechanisms of starvation-induced autophagy in Saccharomyces cerevisiae. Four research papers were shortlisted in this review following the inclusion and exclusion criteria. We observed a commonly shared pathway undertaken by S. cerevisiae under nutritional stress. Targeted and untargeted metabolomics was applied in either of these studies using varying platforms resulting in the annotation of several different observable metabolites. We saw a commonly shared pathway undertaken by S. cerevisiae under nutritional stress. Following nitrogen starvation, the concentration of cellular nucleosides was altered as a result of autophagic RNA degradation. Additionally, it is also found that autophagy replenishes amino acid pools to sustain macromolecule synthesis. Furthermore, in glucose starvation, nucleosides were broken down into carbonaceous metabolites that are being funneled into the non-oxidative pentose phosphate pathway. The ribose salvage allows for the survival of starved yeast. Moreover, acute glucose starvation showed autophagy to be involved in maintaining ATP/energy levels. We highlighted the practicality of metabolomics as a tool to better understand the underlying mechanisms involved to maintain homeostasis by recycling degradative products to ensure the survival of S. cerevisiae under starvation. The application of metabolomics has extended the scope of autophagy and provided newer intervention targets against cancer as well as neurodegenerative diseases in which autophagy is implicated. Full article

Cordyceps militaris is an entomopathogenic ascomycete with similar pharmacological importance to that of the wild caterpillar fungus Ophiocordyceps sinensis. C. militaris has attracted significant research and commercial interest due to its content in bioactive compounds beneficial to human health and the relative ease of cultivation under laboratory conditions. However, room for improvement exists in the commercial-scale cultivation of C. militaris and concerns issues principally related to appropriate strain selection, genetic degeneration of cultures, and substrate optimization. In particular, culture degeneration—usually expressed by abnormal fruit body formation and reduced sporulation—results in important economic losses and is holding back investors and potential growers (mainly in Western countries) from further developing this highly promising sector. In the present review, the main factors that influence the generation of biomass and metabolites (with emphasis on cordycepin biosynthesis) by C. militaris are presented and evaluated in conjunction with the use of a wide range of supplements or additives towards the enhancement of fungal productivity in large-scale cultivation processes. Moreover, physiological and genetic factors that increase or reduce the manifestation of strain degeneration in C. militaris are outlined. Finally, methodologies for developing protocols to be used in C. militaris functional biology studies are discussed. Full article

Mucormycosis, a secondary fungal infection, gained much attention in the ongoing COVID-19 pandemic. This deadly infection has a high all-cause mortality rate and imposes a significant economic, epidemiological, and humanistic burden on the patients and healthcare system. Evidence from the published epidemiological studies showed the varying prevalence of COVID-19-associated mucormycosis (CAM). This study aims to compute the pooled prevalence of CAM and other associated clinical outcomes. MEDLINE, Embase, Cochrane COVID-19 Study Register, and WHO COVID-19 databases were scanned to retrieve the relevant articles until August 2021. All studies reporting the prevalence of mucormycosis among COVID-19 patients were eligible for inclusion. Two investigators independently screened the articles against the selection criteria, extracted the data, and performed the quality assessment using the JBI tool. The pooled prevalence of CAM was the primary outcome, and the pooled prevalence of diabetes, steroid exposure, and the mortality rate were the secondary outcomes of interest. Comprehensive Meta-Analysis software version 2 was used for performing the meta-analysis. This meta-analysis comprised six studies with a pooled sample size of 52,916 COVID-19 patients with a mean age of 62.12 ± 9.69 years. The mean duration of mucormycosis onset was 14.59 ± 6.88 days after the COVID-19 diagnosis. The pooled prevalence of CAM (seven cases per 1000 patients) was 50 times higher than the highest recorded background of mucormycosis (0.14 cases per 1000 patients). A high mortality rate was found among CAM patients with a pooled prevalence rate of 29.6% (95% CI: 17.2–45.9%). Optimal glycemic control and the judicious use of steroids should be the approach for tackling rising CAM cases. Full article

Entomopathogenic fungi (EF), who represent active agents to control insect natural populations, usually persist in terrestrial habitats. Southwest area in China has various climate conditions and abundant plant biodiversity (crop, forest, grassy, orchard and arable areas). Nevertheless, the potential of soil-inhabitant EF as insect pest biocontrol agents, is unknown. In this study, first the EF biodiversity from soil of three provinces (Guizhou, Sichuan, and Yunnan) was surveyed. Then, the virulence of 29 isolated strains against Bemesia tabaci and Spodoptera litura was assessed. After analyzing 212 soil samples, 497 isolated fungi were identified. Out of them, 490 isolates were classified in 45 species of 24 genera, whereas the other seven isolates, belonging to Paecilomyces and Purpureocillium genera, were not identified under species level. Furthermore, the EF biodiversity from soil of Sichuan, Yunan, and Guizhou areas, analyzed by Shannon Wiener Index (SWI) was rated at 2.98, 1.89, and 2.14, while SWIs-biodiversity in crop, forest, grassy, orchard and arable areas was rated at 2.88, 2.74, 3.05, 2.39, and 2.47. SWI data suggested that soil from Sichuan area and grassy had higher EF biodiversity compared with other analyzed provinces and areas. Virulence bioassay results indicated that, out of the 29 isolates tested, 24 were pathogenic against B. tabaci and S. litura, resulting in mortality rates >10%. In conclusion, this study reports the EF distribution and biodiversity in soil from three provinces located at Southwest China, whereas their potential use as a tool for the B. tabaci and S. litura biocontrol must be further investigated. Full article

Numerous reports describe the emergence of resistance in dermatophytes, especially in T. rubrum and T. mentagrophytes/indotineae strains. We here present a review of the current status of resistance in dermatophytes worldwide. Resistance to terbinafine is mainly discussed, with different mutations found in the squalene epoxidase gene also considered. Resistance to azoles is also approached. Clinical presentations caused by resistant dermatophytes are presented, together with alternative therapies that help to better manage these kind of infections. Full article

Fibrodontia is a genus of wood-inhabiting fungi consisting of four species so far, including F. gossypina as generic type. Two new species, Fibrodontia austrosinensis and F. subalba, are described and illustrated from China. Fibrodontia austrosinensis from southwestern China is characterized by a grandinioid to odontioid hymenophore with numerous small aculei, a dimitic hyphal system with scattered, smooth skeletal hyphae and ellipsoid basidiospores measuring 4.2–5.2 × 3.5–4.5 μm. Fibrodontia subalba from the West Tianshan Mountain in northwestern China is distinguished by an odontioid to hydnoid hymenophore, a dimitic hyphal system, and ellipsoid basidiospores measuring 3.7–4.4 × 2.8–3.4 μm. The phylogenies inferred from the data set of nuc rDNA ITS1-5.8S-ITS2 (ITS) and D1–D2 domains of nuc 28S rDNA (28S), and that of ITS, 28S, translation elongation factor (tef1α), and RNA polymerase II second largest subunit (rpb2) supported Fibrodontia as a monophyletic genus in the Trechisporales, and F. austrosinensis and F. subalba as separate lineages within Fibrodontia. Multi-rate Poisson Tree Processes, Automatic Barcode Gap Discovery and genetic distance methods based on ITS sequences of Fibrodontia also supported F. austrosinensis and F. subalba as distinct species. The taxonomic status of F. fimbriata that was recently transferred from Cystidiodendron, is briefly discussed. A key to all six known species of Fibrodontia is provided. Full article

The stress response gene DDR48 has been characterized in Saccharomyces cerevisiae and Candida albicans to be involved in combating various cellular stressors, from oxidative agents to antifungal compounds. Surprisingly, the biological function of DDR48 has yet to be identified, though it is likely an important part of the stress response. To gain insight into its function, we characterized DDR48 in the dimorphic fungal pathogen Histoplasma capsulatum. Transcriptional analyses showed preferential expression of DDR48 in the mycelial phase. Induction of DDR48 in Histoplasma yeasts developed after treatment with various cellular stress compounds. We generated a ddr48∆ deletion mutant to further characterize DDR48 function. Loss of DDR48 alters the transcriptional profile of the oxidative stress response and membrane synthesis pathways. Treatment with ROS or antifungal compounds reduced survival of ddr48∆ yeasts compared to controls, consistent with an aberrant cellular stress response. In addition, we infected RAW 264.7 macrophages with DDR48-expressing and ddr48∆ yeasts and observed a 50% decrease in recovery of ddr48∆ yeasts compared to wild-type yeasts. Loss of DDR48 function results in numerous negative effects in Histoplasma yeasts, highlighting its role as a key player in the global sensing and response to cellular stress by fungi. Full article

Cryptococcosis is a systemic fungal disease acquired from contaminated environments with propagules of the basidiomycetous yeasts of the Cryptococcus neoformans and C. gattii species complexes. The C. neoformans species complex classically comprises four major molecular types (VNI, VNII, VNIII, and VNIV), and the C. gattii species complex comprises another four (VGI, VGII, VGIII, and VGIV) and the newly identified molecular type VGV. These major molecular types differ in their epidemiological and ecological features, clinical presentations, and therapeutic outcomes. Generally, the most common isolated types are VNI, VGI, and VGII. The epidemiological profile of cryptococcosis in domestic cats is poorly studied and cats can be the sentinels for human infections. Therefore, the present study aimed to determine the molecular characterization of Cryptococcus spp. isolated from domestic cats and their dwellings in the metropolitan area of Rio de Janeiro, Brazil. A total of 36 Cryptococcus spp. strains, both clinical and environmental, from 19 cats were subtyped using multilocus sequence typing (MLST). The ploidy was identified using flow cytometry and the mating type was determined through amplification with specific pheromone primers. All strains were mating type alpha and 6/36 were diploid (all VNII). Most isolates (63.88%) were identified as VNII, a rare molecular type, leading to the consideration that this genotype is more likely related to skin lesions, since there was a high percentage (68.75%) of cats with skin lesions, which is also considered rare. Further studies regarding the molecular epidemiology of cryptococcosis in felines are still needed to clarify the reason for the large proportion of the rare molecular type VNII causing infections in cats. Full article

Pneumocystis spp. was discovered in 1909 and was classified as a fungus in 1988. The species that infects humans is called P. jirovecii and important characteristics of its genome have recently been discovered. Important advances have been made to understand P. jirovecii, including aspects of its biology, evolution, lifecycle, and pathogenesis; it is now considered that the main route of transmission is airborne and that the infectious form is the asci (cyst), but it is unclear whether there is transmission by direct contact or droplet spread. On the other hand, P. jirovecii has been detected in respiratory secretions of hosts without causing disease, which has been termed asymptomatic carrier status or colonization (frequency in immunocompetent patients: 0–65%, pregnancy: 15.5%, children: 0–100%, HIV-positive patients: 20–69%, cystic fibrosis: 1–22%, and COPD: 16–55%). This article briefly describes the history of its discovery and the nomenclature of Pneumocystis spp., recently uncovered characteristics of its genome, and what research has been done on the transmission and colonization of P. jirovecii. Based on the literature, the authors of this review propose a hypothetical natural history of P. jirovecii infection in humans. Full article

Plant-associated fungi, or the mycobiome, inhabit plant surfaces above ground, reside in plant tissues as endophytes, or are rhizosphere in the narrow zone of soil surrounding plant roots. Studies have characterized mycobiomes of various plant species, but little is known about the sorghum mycobiome, especially in Africa, despite sorghum being one of the most important indigenous and commercial cereals in Africa. In this study, the mycobiome associated with above- and below-ground tissues of three commercial sorghum cultivars, as well as from rhizosphere and surrounding bulk soil samples, were sequenced using targeted sequencing with the Illumina MiSeq platform. Relative abundance differences between fungal communities were found between above-ground and below-ground niches, with most differences mostly in the dominant MOTUs, such as Davidiellaceae sp. (Cladosporium), Didymellaceae sp. 1 (Phoma), Fusarium, Cryptococcus and Mucor. Above-ground communities also appeared to be more diverse than below-ground communities, and plants harboured the most diversity. A considerable number of MOTUs were shared between the cultivars although, especially for NS5511, their abundances often differed. Several of the detected fungal groups include species that are plant pathogens of sorghum, such as Fusarium, and, at low levels, Alternaria and the Ustilaginomycetes. Findings from this study illustrate the usefulness of targeted sequencing of the ITS rDNA gene region (ITS2) to survey and monitor sorghum fungal communities and those from associated soils. This knowledge may provide tools for disease management and crop production and improvement. Full article

Fusarium graminearum (Fgr) is a devastating filamentous fungal pathogen that causes diseases in cereals, while producing mycotoxins that are toxic for humans and animals, and render grains unusable. Low efficiency in managing Fgr poses a constant need for identifying novel control mechanisms. Evidence that fungal extracellular vesicles (EVs) from pathogenic yeast have a role in human disease led us to question whether this is also true for fungal plant pathogens. We separated EVs from Fgr and performed a proteomic analysis to determine if EVs carry proteins with potential roles in pathogenesis. We revealed that protein effectors, which are crucial for fungal virulence, were detected in EV preparations and some of them did not contain predicted secretion signals. Furthermore, a transcriptomic analysis of corn (Zea mays) plants infected by Fgr revealed that the genes of some of the effectors were highly expressed in vivo, suggesting that the Fgr EVs are a mechanism for the unconventional secretion of effectors and virulence factors. Our results expand the knowledge on fungal EVs in plant pathogenesis and cross-kingdom communication, and may contribute to the discovery of new antifungals. Full article

Endophytic fungi (EPF) and arbuscular mycorrhizal fungi (AMF) symbioses can promote the growth and productivity of several types of plants. This work aimed to investigate the effect of co-inoculation of an EPF Exserohilum rostratum NMS1.5 and an AMF Glomus etunicatum UDCN52867 g.5 on the growth and yields of sunchoke (Helianthus tuberosus L.) compared to the effects of full-dose and half-dose chemical fertilizer (15–15–15) under field conditions. Several plant growth parameters of the co-inoculated plants were significantly higher than the other treatments. Remarkably, such an effect was relatively equal to that of the full-dose chemical fertilizers. Moreover, the co-inoculation of EPF and AMF significantly improved the tuber yield production, even better than the use of a chemical fertilizer. This is the first report to show that plant growth promoting effects of the co-inoculation of EPF and AMF were exceptionally greater than those of the chemical fertilizer. Therefore, our EPF and AMF could potentially be used as a biofertilizer for promoting the growth and yield of sunchoke in the fields. Full article

We conducted population pharmacokinetic (PPK) analysis and Monte Carlo simulations to determine the appropriate prophylactic dose of fluconazole to prevent invasive candidiasis in patients with hematological malignancies. Patients receiving chemotherapy or hematopoietic stem cell transplantation at Yokohama City University Hospital between November 2018 and March 2020 were included. Additionally, patients receiving oral fluconazole for prophylaxis were recruited. We set the free area under the curve/minimum inhibitory concentration (MIC) = 50 as the target and determined the largest MIC (breakpoint MIC) that could achieve more than 90% probability of target attainment. The blood fluconazole concentration of 54 patients (119 points) was used for PPK analysis. The optimal model was the one-compartment model with first-order administration and first-order elimination incorporating creatinine clearance (CLcr) as a covariate of clearance and body weight as a covariate of distribution volume. We conducted Monte Carlo simulation with fluconazole at 200 mg/day or 400 mg/day dosing schedules and patient body weight and CLcr ranging from 40 to 70 kg and 40–140 mL/min, respectively. The breakpoint MICs on the first dosing day and at steady state were 0.5–1.0 μg/mL and 1.0–2.0 μg/mL for 200 mg/day and 1.0–2.0 μg/mL and 2.0–4.0 μg/mL for 400 mg/day, respectively. The recommended dose was 400–700 mg/day for the loading dose and 200–400 mg/day for the maintenance dose. Our findings suggest that the optimal prophylactic dose of fluconazole in hematological malignancy patients depends on CLcr and body weight, and a sufficient loading and maintenance dose may be needed to completely prevent invasive candidiasis. Full article

Alternaria alternata is the most important allergenic fungus, with up to 20% of allergic patients affected. The sensitization profile of patients sensitized to A. alternata and how it changes when treated with immunotherapy is not known. Our objective is to determine the allergen recognition pattern of allergic patients to A. alternata and to study its association to the parameters studied in a clinical trial recently published. Sera of 64 patients from the clinical trial of immunotherapy with native major allergen Alt a 1 were analyzed by immunoblotting; 98. 4% of the patients recognized Alt a 1. The percentage of recognition for Alt a 3, Alt a 4, and/or Alt a 6, Alt a 7, Alt a 8, Alt a 10 and/or Alt a 15 was 1.6%, 21.9%, 12.5%, 12.5%, and 12.5% respectively. Of the 64 patients, 45 (70.3%) only recognized Alt a 1 among the allergens present in the A. alternata extract. Immunotherapy with Alt a 1 desensitizes treated patients, reducing their symptoms and medication consumption through the elimination of Alt a 1 sensitization, which is no longer present in the immunoblotting of some patients. There may be gender differences in the pattern of sensitization to A. alternata allergens, among others. Full article

Solid-based residues (SBRs) left from harvesting the fruiting bodies of cultured Cordyceps mushrooms are a challenge to sustainability. Therefore, in this study, the SBRs from the cultivation of Cordyceps militaris (C. militaris) via solid-state fermentation (SSF) were employed to prepare crude extracts, with the aim of considering their possible use in cosmetics. The SBRs obtained from cultivation with solid media containing defatted rice bran mixed with barley, white rice, Riceberry rice, and wheat were named SBR-B, SBR-R, SBR-Rb, and SRB-W, respectively. They were extracted with solvents of differing polarity and then evaluated for their total phenolic content (TPC), total flavonoid content (TFC), and total carbohydrate content (TCC). In addition, antioxidant and tyrosinase inhibitory activities, photoprotection, and cytotoxicity were also assessed. The results revealed that the total bioactive contents and biological capacities of crude SBR extracts were significantly influenced by the types of SBR and extraction solvent (p < 0.05). The SBR-B extracted with hot water exhibited the highest antioxidant activity (66.62 ± 2.10, 212.00 ± 3.43, and 101.62 ± 4.42 mg TEAC/g extract) when assayed by DPPH, ABTS, and FRAP methods, respectively, whereas tyrosinase inhibitory activity (51.13 ± 1.11 mg KAE/g extract) with 90.43 ± 1.96% inhibition at 1 mg/mL was excellently achieved by SBR-Rb extracted by 50% (v/v) ethanol. Correlations between bioactive contents in the crude extracts and their biological activities were mostly proven at a strong level (p < 0.01). The capability of the crude extracts to absorb UV over the range of 290–330 nm disclosed their potential roles as natural UV absorbers and boosters. Cytotoxicity analysis using fibroblast cell lines tested with hot water and 50% (v/v) ethanolic SBR extracts demonstrated safe use within a concentration range of 0.001–10 mg/mL. Interestingly, their fibroblast proliferative capacity, indicating anti-aging properties, was highly promoted. The chemical composition analyzed via LC–MS/MS techniques showed that seven phenolic acids and four flavonoids were identified in the crude SBR extracts. Furthermore, the other compounds present included nucleosides, nucleobases, amino acids, sugars, phospholipids, alkaloids, organic acids, vitamins, and peptides. Therefore, it is emphasized that SBRs from C. militaris can be a prospective source for preparing crude extracts employed in cosmetics. Lastly, they could be further utilized as multifunctional ingredients in cosmetics and cosmeceuticals. Full article

Plants can ‘catch’ and mitigate airborne pollutants and are assisted by fungi inhabiting their leaves. The structure and function of the fungal communities inhabiting the phyllosphere of hornbeam trees growing in two chronically polluted areas, the oilfield of Bóbrka and the city center of Warsaw, were compared to the ones growing in one nature reserve, the Białowieża National Park. Fungi were isolated and characterized both phylogenetically and functionally for their potential role in air pollution mitigation. Both culture-dependent (e.g., enzyme assays and tolerance tests) and culture-independent methods (e.g., ITS and shotgun sequencings) were used. Furthermore, the degradation potential of the fungi was assessed by gas chromatography mass spectrometry (GC-MS). Shotgun sequencing showed that the phyllosphere fungal communities were dominated by fungi belonging to the phylum Ascomycota. Aureobasidium was the only genus detected at the three locations with a relative abundance ≥1.0%. Among the cultivated epiphytic fungi from Bóbrka, Fusarium sporotrichioides AT11, Phoma herbarum AT15, and Lophiostoma sp. AT37 showed in vitro aromatic hydrocarbon degradation potential with laccase activities of 1.24, 3.62, and 7.2 μU L⁻¹, respectively, and peroxidase enzymes with activities of 3.46, 2.28, and 7.49 μU L⁻¹, respectively. Furthermore, Fusarium sporotrichioides AT11 and Phoma herbarum AT15 tolerated exposure to airborne naphthalene and benzene. Lophiostoma sp. AT37 was the most tolerant to exposure to these pollutants, in line with being the best potential aromatic hydrocarbon degrader isolated in this study. Full article

Phenoxazine derivatives such as Nile Blue analogues are assumed to be increasingly relevant in cell biology due to their fluorescence staining capabilities and antifungal and anticancer activities. However, the mechanisms underlying their effects remain poorly elucidated. Using S. cerevisiae as a eukaryotic model, we found that BaP1, a novel 5- and 9-N-substituted benzo[a]phenoxazine synthesized in our laboratory, when used in low concentrations, accumulates and stains the vacuolar membrane and the endoplasmic reticulum. In contrast, at higher concentrations, BaP1 stains lipid droplets and induces a regulated cell death process mediated by vacuolar membrane permeabilization. BaP1 also induced mitochondrial fragmentation and depolarization but did not lead to ROS accumulation, changes in intracellular Ca²⁺, or loss of plasma membrane integrity. Additionally, our results show that the cell death process is dependent on the vacuolar protease Pep4p and that the vacuole permeabilization results in its translocation from the vacuole to the cytosol. In addition, although nucleic acids are commonly described as targets of benzo[a]phenoxazines, we did not find any alterations at the DNA level. Our observations highlight BaP1 as a promising molecule for pharmacological application, using vacuole membrane permeabilization as a targeted approach. Full article

Botrytis cinerea is a ubiquitous necrotrophic pathogen causing grey mould in economically important crops. Light effect in horticulture is undeniable and fungi also react to light. Selected specific light-emitting diodes (LEDs) and photoperiods can be used for fungal pathogen inhibition. This study aimed to evaluate how LED light wavelengths and photoperiods affect the growth parameters of B. cinerea. The morphological (mycelium appearance, sclerotia distribution) and phenotypic (conidia presence and size, mycelium growth rate, recovery) characteristics of the fungal pathogen B. cinerea were evaluated under royal blue 455 nm, blue 470 nm, cyan 505 nm, yellow 590 nm, and red 627 nm LED lights at various photoperiods (4, 8, 12, 16, 20, 24 h). The results revealed that the light conditions and photoperiods influenced the B. cinerea morphological and phenotypic characteristics. Overall, the highest B. cinerea inhibition was under yellow (590 nm) LED light at 4 and 8 h photoperiods. Conidia did not form under blue 455 nm at 8, 16, 20, and 24 h photoperiods. Therefore, it can be assumed that the phenotypic and morphological features of B. cinerea depend on the specific photoperiod and LED light wavelength. The results allowed an exploration of original research approaches, raised new scientific questions for further investigation, and suggested new green plant protection solutions. Full article

Bark cankers accompanied by symptoms of decline and dieback are the result of a destructive disease caused by Phytophthora infections in woody plants. Pathogenicity, gas exchange, chlorophyll a fluorescence, and volatile responses to P. cactorum and P. plurivora inoculations were studied in field-grown 10-year-old hybrid poplar plants. The most stressful effects of P. cactorum on photosynthetic behaviour were found at days 30 and 38 post-inoculation (p.-i.), whereas major disturbances induced by P. plurivora were identified at day 30 p.-i. and also belatedly at day 52 p.-i. The spectrum of volatile organic compounds emitted at day 98 p.-i. was richer than that at day 9 p.-i, and the emissions of both sesquiterpenes α-cubebene and germacrene D were induced solely by the Phytophthora inoculations. Significant positive relationships were found between both the axial and the tangential development of bark cankers and the emissions of α-cubebene and β-caryophyllene, respectively. These results show that both α-cubebene and germacrene D are signal molecules for the suppression of Phytophthora hyphae spread from necrotic sites of the bark to healthy living tissues. Four years following inoculations, for the majority of the inoculated plants, the callus tissue had already closed over the bark cankers. Full article

The contribution of fungi to the degradation of plant litter and transformation of dissolved organic matter (humic substances, in particular) in freshwater ecosystems has received increasing attention recently. However, the role of Saprolegniales as one of the most common eukaryotic organisms is rarely studied. In this study, we isolated and phylogenetically placed 51 fungal and 62 Saprolegniales strains from 12 German lakes. We studied the cellulo-, lignino-, and chitinolytic activity of the strains using plate assays. Furthermore, we determined the capacity of 10 selected strains to utilize 95 different labile compounds, using Biolog FF MicroPlates™. Finally, the ability of three selected strains to utilize maltose and degrade/produce humic substances was measured. Cladosporium and Penicillium were amongst the most prevalent fungal strains, while Saprolegnia, Achlya, and Leptolegnia were the most frequent Saprolegniales strains. Although the isolated strains assigned to genera were phylogenetically similar, their enzymatic activity and physiological profiling were quite diverse. Our results indicate that Saprolegniales, in contrast to fungi, lack ligninolytic activity and are not involved in the production/transformation of humic substances. We hypothesize that Saprolegniales and fungi might have complementary roles in interacting with dissolved organic matter, which has ecological implications for carbon cycling in freshwater ecosystems. Full article

Oleaginous yeast Rhodosporidium toruloides has great biotechnological potential and scientific interest, yet the molecular rationale of its cellular behavior to carbon and nitrogen ratios with concurrent lipid agglomeration remains elusive. Here, metabolomics adaptations of the R. toruloides in response to varying glucose and nitrogen concentrations have been investigated. In preliminary screening we found that 5% glucose (w/v) was optimal for further analysis in Rhodosporidium toruloides 3641. Hereafter, the effect of complementation to increase lipid agglomeration was evaluated with different nitrogen sources and their concentration. The results obtained illustrated that the biomass (13 g/L) and lipid (9.1 g/L) production were maximum on 5% (w/v) glucose and 0.12% (NH₄)₂SO₄. Furthermore, to shed lights on lipid accumulation induced by nitrogen-limitation, we performed metabolomic analysis of the oleaginous yeast R. toruloides 3641. Significant changes were observed in metabolite concentrations by qualitative metabolomics through gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), which were mapped onto the governing metabolic pathways. Notable finding in this strain concerns glycerol and CDP-DAG metabolism wherein reduced production of glycerol and phospholipids induced a bypass leading to enhanced de-novo triacylglyceride synthesis. Collectively, our findings help in understanding the central carbon metabolism of R. toruloides which may assist in developing rationale metabolic models and engineering efforts in this organism. Full article