Enhanced resistance to heat and fungal infection in transgenic Trichoderma via over-expressing the HSP70 gene.

Heat stress is one of the major abiotic stresses affecting the growth, sporulation, colonization and survival of Trichoderma viride. This study aimed to gain a better insight into the underlying mechanism governing the heat stress response of T. viride Tv-1511. We analysed the transcriptomic changes of Tv-1511 under normal and heat stress conditions using RNA sequencing. We observed that Tv-1511 regulates the biosynthesis of secondary metabolites through a complex network of signalling pathways. Additionally, it significantly activates the anti-oxidant defence system, heat shock proteins and stress-response-related transcription factors in response to heat stress. TvHSP70 was identified as a key gene, and transgenic Tv-1511 overexpressing TvHSP70 (TvHSP70-OE) was generated. We conducted an integrated morphological, physiological and molecular analyses of the TvHSP70-OE and wild-type strains. We observed that TvHSP70 over-expression significantly triggered the growth, anti-oxidant capacity, anti-fungal activity and growth-promoting ability of Tv-1511. Regarding anti-oxidant capacity, TvHSP70 primarily up-regulated genes involved in enzymatic and non-enzymatic anti-oxidant systems. In terms of anti-fungal activity, TvHSP70 primarily activated genes involved in the synthesis of enediyne, anti-fungal and aminoglycoside antibiotics. This study provides a comparative analysis of the functional significance and molecular mechanisms of HSP70 in Trichoderma. These findings provide a valuable foundation for further analyses.

Posaconazole versus voriconazole as antifungal prophylaxis for invasive fungal diseases in patients with hematological malignancies.

INTRODUCTION: The incidence of invasive fungal diseases (IFDs) has risen in hematologic malignancy patients due to neutropenia. While posaconazole is recommended as the first-line antifungal prophylaxis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients and voriconazole is an alternative, there is currently no direct comparison data available to assess their relative effectiveness. METHOD: We retrospectively reviewed eligible patient charts from January 2017 to February 2019 to identify breakthrough IFD rates, drug adverse event frequency, and drug acquisition cost in AML/MDS patients. RESULTS: Forty-eight patients received 130 chemo cycles, with 50 (38%) cycles prescribed posaconazole and 80 (62%) prescribed voriconazole as primary IFD prophylaxis. The incidence rates of IFD in the posaconazole group were 8% (4 out of 50), of which two were probable and two were possible infections, while 6.26% (5 out of 80) of patients in the voriconazole group developed IFD, with four possible infections and one probable infection (p = 0.73). A higher percentage of patients in the voriconazole group discontinued prophylaxis due to adverse events, with six patients compared to two patients in the posaconazole group (p = 0.15). The drug acquisition cost of posaconazole is 5.62 times more expensive than voriconazole. CONCLUSION: The use of voriconazole instead of posaconazole for 130 chemo cycles would save $166,584.6. Posaconazole and voriconazole have comparable efficacy and safety in preventing IFD in AML and MDS patients receiving chemotherapy. However, posaconazole is more costly than voriconazole.

Fungal biomineralization of toxic metals accelerates organic pollutant removal.

Fungal biomineralization plays an important role in the biogeochemical cycling of metals in the environment and has been extensively explored for bioremediation and element biorecovery. However, the cellular and metabolic responses of fungi in the presence of toxic metals during biomineralization and their impact on organic matter transformations are unclear. This is an important question because co-contamination by toxic metals and organic pollutants is a common phenomenon in the natural environment. In this research, the biomineralization process and oxidative stress response of the geoactive soil fungus Aspergillus niger were investigated in the presence of toxic metals (Co, Cu, Mn, and Fe) and the azo dye orange II (AO II). We have found that the co-existence of toxic metals and AO II not only enhanced the fungal biomineralization of toxic metals but also accelerated the removal of AO II. We hypothesize that the fungus and in situ mycogenic biominerals (toxic metal oxalates) constituted a quasi-bioreactor, where the biominerals removed organic pollutants by catalyzing reactive oxygen species (ROS) generation resulting from oxidative stress. We have therefore demonstrated that a fungal/biomineral system can successfully achieve the goal of toxic metal immobilization and organic pollutant decomposition. Such findings inform the potential development of fungal-biomineral hybrid systems for mixed pollutant bioremediation as well as provide further understanding of fungal organic-inorganic pollutant transformations in the environment and their importance in biogeochemical cycles.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

BACKGROUND: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018 - 2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n= 10), mucormycosis (n= 8), histoplasmosis (n= 2), cryptococcosis (n= 2), and others (n= 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSIONS: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Aflatoxin profiles of Aspergillus flavus isolates in Sudanese fungal rhinosinusitis.

Aspergillus flavus is a commonly encountered pathogen responsible for fungal rhinosinusitis (FRS) in arid regions. The species is known to produce aflatoxins, posing a significant risk to human health. This study aimed to investigate the aflatoxin profiles of A. flavus isolates causing FRS in Sudan. A total of 93 clinical and 34 environmental A. flavus isolates were studied. Aflatoxin profiles were evaluated by phenotypic (thin-layer and high-performance chromatography) and genotypic methods at various temperatures and substrates. Gene expression of aflD and aflR was also analyzed. A total of 42/93 (45%) isolates were positive for aflatoxin B1 and AFB2 by HPLC. When the incubation temperature changed from 28°C to 36°C, the number of positive isolates decreased to 41% (38/93). Genetic analysis revealed that 85% (79/93) of clinical isolates possessed all seven aflatoxin biosynthesis-associated genes, while 27% (14/51) of non-producing isolates lacked specific genes (aflD/aflR/aflS). Mutations were observed in aflS and aflR genes across both aflatoxin-producers and non-producers. Gene expression of aflD and aflR showed the highest expression between the 4th and 6th days of incubation on the Sabouraud medium and on the 9th day of incubation on the RPMI (Roswell Park Memorial Institute) medium. Aspergillus flavus clinical isolates demonstrated aflatoxigenic capabilities, influenced by incubation temperature and substrate. Dynamic aflD and aflR gene expression patterns over time enriched our understanding of aflatoxin production regulation. The overall findings underscored the health risks of Sudanese patients infected by this species, emphasizing the importance of monitoring aflatoxin exposure.

Aspergillus flavus, mainly causing fungal rhinosinusitis in Sudan, poses health risks due to aflatoxin production. This study revealed diverse levels of aflatoxin and gene expression of clinical isolates by pheno- and genotypic methods, emphasizing the need for vigilant monitoring in the region.

A global survey of host, aquatic, and soil microbiomes reveals shared abundance and genomic features between bacterial and fungal generalists.

Environmental change, coupled with alteration in human lifestyles, is profoundly impacting the microbial communities critical to the health of the Earth and its inhabitants. To identify bacteria and fungi that are resistant and susceptible to habitat change, we analyze thousands of genera detected in 1,580 host, soil, and aquatic samples. This large-scale analysis identifies 48 bacterial and 4 fungal genera that are abundant across the three biomes, demonstrating fitness in diverse environmental conditions. Samples containing these generalists have significantly higher alpha diversity. These generalists play a significant role in shaping cross-kingdom community structure, boasting larger genomes with more secondary metabolism and antimicrobial resistance genes. Conversely, 30 bacterial and 19 fungal genera are only found in a single habitat, suggesting a limited ability to adapt to different and changing environments. These findings contribute to our understanding of microbial niche breadth and its consequences for global biodiversity loss.

Application and evaluation of topical amphotericin B for the treatment of respiratory fungal infections.

BACKGROUND: In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections. METHODS: We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023. RESULTS: Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects. CONCLUSION: The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

Mix-method toolbox for monitoring greenhouse gas production and microbiome responses to soil amendments.

In this study, we adopt an interdisciplinary approach, integrating agronomic field experiments with soil chemistry, molecular biology techniques, and statistics to investigate the impact of organic residue amendments, such as vinasse (a by-product of sugarcane ethanol production), on soil microbiome and greenhouse gas (GHG) production. The research investigates the effects of distinct disturbances, including organic residue application alone or combined with inorganic N fertilizer on the environment. The methods assess soil microbiome dynamics (composition and function), GHG emissions, and plant productivity. Detailed steps for field experimental setup, soil sampling, soil chemical analyses, determination of bacterial and fungal community diversity, quantification of genes related to nitrification and denitrification pathways, measurement and analysis of gas fluxes (N2O, CH4, and CO2), and determination of plant productivity are provided. The outcomes of the methods are detailed in our publications (Lourenço et al., 2018a; Lourenço et al., 2018b; Lourenço et al., 2019; Lourenço et al., 2020). Additionally, the statistical methods and scripts used for analyzing large datasets are outlined. The aim is to assist researchers by addressing common challenges in large-scale field experiments, offering practical recommendations to avoid common pitfalls, and proposing potential analyses, thereby encouraging collaboration among diverse research groups.•Interdisciplinary methods and scientific questions allow for exploring broader interconnected environmental problems.•The proposed method can serve as a model and protocol for evaluating the impact of soil amendments on soil microbiome, GHG emissions, and plant productivity, promoting more sustainable management practices.•Time-series data can offer detailed insights into specific ecosystems, particularly concerning soil microbiota (taxonomy and functions).

Characterization of a broad-spectrum antifungal strain, Streptomyces graminearus STR-1, against Magnaporthe oryzae.

Fungal diseases such as the devastating rice blast pose severe threats to crop production worldwide. Biological control of crop diseases caused by fungal pathogens is an environment-friendly approach for safeguarding crop production. But the insufficient availability of microbial agents effective against various fungal diseases has hampered the development of green production in crops. In this study, we identified a broad-spectrum antifungal bacterium, Streptomyces graminearus STR-1, showing antagonistic activity to diverse fungal pathogens including Magnaporthe oryzae, Rhizoctonia solani, Fusarium graminearum, Ustilaginoidea virens, and Bipolaris maydis. Its antifungal activity was relatively stable and less affected by temperature and pH. Evaluation of the biocontrol activity of STR-1 revealed that STR-1 prevented and controlled rice blast disease via eliciting plant immunity and suppressing fungal infection-structure development. STR-1 broth extract inhibited spore germination, likely through inhibiting protein synthesis. Combining LC-MS and chromatography analysis of the antimicrobial compounds purified from STR-1 broth extract, together with decoding STR-1 genomic sequence, we identified 4-oxo-4-[(1-phenylethyl)amino]but-2-enoic acid, 1,3,5-Trimethylpyrazole and SMA-1 as the potential main STR-1 secondary metabolites associated with its antifungal effects. This study suggests that bacterial strain STR-1 could be used for identifying highly effective and broad-spectrum secondary metabolites for containing rice blast and other crop diseases. The application of the active compounds offers a promising measure to tackle fungal disease.

Sporotrichosis Cluster in Domestic Cats and Veterinary Technician, Kansas, USA, 2022.

We describe a feline sporotrichosis cluster and zoonotic transmission between one of the affected cats and a technician at a veterinary clinic in Kansas, USA. Increased awareness of sporotrichosis and the potential for zoonotic transmission could help veterinary professionals manage feline cases and take precautions to prevent human acquisition.

A Study of Metabolites from Basidiomycota and Their Activities against Pseudomonas aeruginosa.

The World Health Organization (WHO) promotes research aimed at developing new drugs from natural compounds. Fungi are important producers of bioactive molecules, and they are often effective against other fungi and/or bacteria and are thus a potential source of new antibiotics. Basidiomycota crude extracts, which have previously been proven to be active against Pseudomonas aeruginosa ATCC27853, were subjected to liquid chromatographic separation by RP-18, leading to six macro-fractions for each fungal extract. The various fractions were tested for their bioactivities against P. aeruginosa ATCC27853, and ten of them were characterized by HPLC-HRMS and NMR. Further chromatographic separations were performed for a few selected macro-fractions, yielding seven pure compounds. Bioactivity was mainly found in the lipophilic fractions containing fatty acids and their derivatives, such as hydroxy or keto C-18 unsaturated acids, and in various complex lipids, such as glycolipids and related compounds. More hydrophilic molecules, such as GABA, phenethylamine, two chromogenic anthraquinoids and pistillarin, were also isolated, and their antibacterial activities were recorded. The novelties of this research are as follows: (i) the genera Cortinarius and Mycena have never been investigated before for the synthesis of antibiotic compounds; (ii) the molecules produced by these genera are known, but their production has never been reported in the investigated fungi; (iii) the determination of bacterial siderophore synthesis inhibition by certain compounds from Cortinarius and Mycena.

Effects of Sodium Alginate and Calcium Chloride on Fungal Growth and Viability in Biomass-Fungi Composite Materials Used for 3D Printing.

To combat climate change, one approach is to manufacture products from biomass-fungi composite materials instead of petroleum-based plastics. These products can be used in packaging, furniture, and construction industries. A 3D printing-based manufacturing method was developed for these biomass-fungi composite materials, eliminating the need for molds, and enabling customized product design. However, previous studies on the 3D printing-based method showed significant shrinkage of printed samples. In this paper, an approach is proposed to reduce the shrinkage by incorporating ionic crosslinking into biomass-fungi composite materials. This paper reports two sets of experiments regarding the effects of sodium alginate (SA) and calcium chloride (CaCl2) on fungal growth and fungal viability. The first set of experiments was conducted using Petri dishes with fungi isolated from colonized biomass-fungi material and different concentrations of SA and CaCl2. Fungal growth was measured by the circumference of fungal colonies. The results showed that concentrations of SA and CaCl2 had significant effects on fungal growth and no fungal growth was observed on Petri dishes with 15% CaCl2. Some of these Petri dishes were also observed under confocal microscopy. The results confirmed the differences obtained by measuring the circumference of fungal colonies. The second set of experiments was conducted using Petri dishes with biomass-fungi mixtures that were treated with different concentrations of SA and exposure times in a CaCl2 (crosslinking) solution. Fungal viability was measured by counting colony-forming units. The results showed that the addition of the SA solution and exposure times in the crosslinking solution had statistically significant effects on fungal viability. The 2SA solution was prepared by dissolving 2 g of SA in 100 mL of water, the 5SA solution was prepared by dissolving 5 g of SA in 100 mL of water, and the crosslinking solution was prepared by dissolving 5 g of CaCl2 in 100 mL of water. The results also showed that fungal viability was not too low in biomass-fungi mixtures that included 2SA solution and were exposed to the crosslinking solution for 1 min.

Marine-Derived Metabolites Act as Promising Antifungal Agents.

The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, and echinocandins, face increasing resistance from pathogenic fungi. Therefore, there is a pressing need for the development of novel antifungal drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures and pharmacological activities. While numerous compounds exhibiting promising antifungal activity have been identified, a comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we have compiled a summary of antifungal compounds derived from marine organisms, highlighting their diverse mechanisms of action targeting various fungal cellular components, including the cell wall, cell membrane, mitochondria, chromosomes, drug efflux pumps, and several biological processes, including vesicular trafficking and the growth of hyphae and biofilms. This review is helpful for the subsequent development of antifungal drugs due to its summary of the antifungal mechanisms of secondary metabolites from marine organisms.

Transcriptome-Wide Identification and Expression Analysis of Genes Encoding Defense-Related Peptides of Filipendula ulmaria in Response to Bipolaris sorokiniana Infection.

Peptides play an essential role in plant development and immunity. Filipendula ulmaria, belonging to the Rosaceae family, is a medicinal plant which exhibits valuable pharmacological properties. F. ulmaria extracts in vitro inhibit the growth of a variety of plant and human pathogens. The role of peptides in defense against pathogens in F. ulmaria remains unknown. The objective of this study was to explore the repertoire of antimicrobial (AMPs) and defense-related signaling peptide genes expressed by F. ulmaria in response to infection with Bipolaris sorokiniana using RNA-seq. Transcriptomes of healthy and infected plants at two time points were sequenced on the Illumina HiSeq500 platform and de novo assembled. A total of 84 peptide genes encoding novel putative AMPs and signaling peptides were predicted in F. ulmaria transcriptomes. They belong to known, as well as new, peptide families. Transcriptional profiling in response to infection disclosed complex expression patterns of peptide genes and identified both up- and down-regulated genes in each family. Among the differentially expressed genes, the vast majority were down-regulated, suggesting suppression of the immune response by the fungus. The expression of 13 peptide genes was up-regulated, indicating their possible involvement in triggering defense response. After functional studies, the encoded peptides can be used in the development of novel biofungicides and resistance inducers.

Characterization of Microbotryum lychnidis-dioicae Secreted Effector Proteins, Their Potential Host Targets, and Localization in a Heterologous Host Plant.

Microbotryum lychnidis-dioicae is an obligate fungal species colonizing the plant host, Silene latifolia. The fungus synthesizes and secretes effector proteins into the plant host during infection to manipulate the host for completion of the fungal lifecycle. The goal of this study was to continue functional characterization of such M. lychnidis-dioicae effectors. Here, we identified three putative effectors and their putative host-plant target proteins. MVLG_02245 is highly upregulated in M. lychnidis-dioicae during infection; yeast two-hybrid analysis suggests it targets a tubulin α-1 chain protein ortholog in the host, Silene latifolia. A potential plant protein interacting with MVLG_06175 was identified as CASP-like protein 2C1 (CASPL2C1), which facilitates the polymerization of the Casparian strip at the endodermal cells. Proteins interacting with MVLG_05122 were identified as CSN5a or 5b, involved in protein turnover. Fluorescently labelled MVLG_06175 and MVLG_05122 were expressed in the heterologous plant, Arabidopsis thaliana. MVLG_06175 formed clustered granules at the tips of trichomes on leaves and in root caps, while MVLG_05122 formed a band structure at the base of leaf trichomes. Plants expressing MVLG_05122 alone were more resistant to infection with Fusarium oxysporum. These results indicate that the fungus might affect the formation of the Casparian strip in the roots and the development of trichomes during infection as well as alter plant innate immunity.

Habitat Diversity, Environmental Conditions, and Distribution of Endangered Fungus Sarcosoma globosum (Ascomycota) in Lithuania.

Sarcosoma globosum (Pezizales, Ascomycota) is a rare and endangered fungus, and it is believed to be extinct in most central European countries. Known records of S. globosum in Lithuania reveal that it is situated on the south-western edge of a shrinking geographical distribution range in Europe. An assessment of the species' current habitat conditions and threats could enhance and provide new knowledge and guidelines to facilitate the efficient conservation of this threatened fungus and its habitats. The main aim of this study was to analyse the habitats and environmental conditions of S. globosum in Lithuania. We examined the diversity of habitats, various soil and tree stand characteristics, forest management activities, and natural disturbances in all 28 known fungus localities. S. globosum habitats in Lithuania are restricted to coniferous forests with the presence of Picea abies; the species was observed in boreo-nemoral bilberry western spruce taiga (the European Nature Information System habitat type T3F14), continental tall-herb western spruce taiga (T3F44), and native fir, spruce, larch, and cedar plantations (T3N1). An analysis of forest stand age structures in Lithuanian S. globosum localities revealed a rather large proportion of young Norway spruce stands of cultural origin (25.6% of study plots were assigned to age classes from 21 to 50 years); nevertheless, the majority of fungus growth sites were situated in older forests. Various natural and anthropogenic disturbances that threaten S. globosum habitats were assessed.

The Known and Unknown "Knowns" of Human Susceptibility to Coccidioidomycosis.

Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis "canon". Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed.

Disseminated Histoplasmosis in a Patient with Myelofibrosis on Ruxolitinib: A Case Report and Review of the Literature on Ruxolitinib-Associated Invasive Fungal Infections.

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies.

Amphotericin B in the Era of New Antifungals: Where Will It Stand?

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

Stephanoascus ciferrii Complex: The Current State of Infections and Drug Resistance in Humans.

In recent years, the incidence of fungal infections in humans has increased dramatically, accompanied by an expansion in the number of species implicated as etiological agents, especially environmental fungi never involved before in human infection. Among fungal pathogens, Candida species are the most common opportunistic fungi that can cause local and systemic infections, especially in immunocompromised individuals. Candida albicans (C. albicans) is the most common causative agent of mucosal and healthcare-associated systemic infections. However, during recent decades, there has been a worrying increase in the number of emerging multi-drug-resistant non-albicans Candida (NAC) species, i.e., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris, and C. ciferrii. In particular, Candida ciferrii, also known as Stephanoascus ciferrii or Trichomonascus ciferrii, is a heterothallic ascomycete yeast-like fungus that has received attention in recent decades as a cause of local and systemic fungal diseases. Today, the new definition of the S. ciferrii complex, which consists of S. ciferrii, Candida allociferrii, and Candida mucifera, was proposed after sequencing the 18S rRNA gene. Currently, the S. ciferrii complex is mostly associated with non-severe ear and eye infections, although a few cases of severe candidemia have been reported in immunocompromised individuals. Low susceptibility to currently available antifungal drugs is a rising concern, especially in NAC species. In this regard, a high rate of resistance to azoles and more recently also to echinocandins has emerged in the S. ciferrii complex. This review focuses on epidemiological, biological, and clinical aspects of the S. ciferrii complex, including its pathogenicity and drug resistance.