Fungal Pathogens Research Articles

Hidden allies: how extracellular vesicles drive biofilm formation, stress adaptation, and host–immune interactions in human fungal pathogens

ABSTRACT Pathogenic fungi pose a significant threat to human health, especially given the rising incidence of invasive fungal infections and the emergence of drug-resistant strains. This requires the development of vaccines and the advancement of antifungal strategies. Recent studies have focused on the roles of fungal extracellular vesicles (EVs) in intercellular communication and host-pathogen interactions. EVs are nanosized, lipid membrane-bound particles that facilitate the transfer of proteins, lipids, and nucleic acids. Here, we review the multifaceted functions of EVs produced by different human fungal pathogens, highlighting their importance in the response of fungal cells to different environmental cues and their interactions with host immune cells. We summarize the current state of research on EVs and how leveraging this knowledge can lead to innovative approaches in vaccine development and antifungal treatment.

Excess mortality of infected ectotherms induced by warming depends on pathogen kingdom and evolutionary history

Climate change is causing extreme heating events and leading to more infectious disease outbreaks, putting species persistence at risk. The extent to which warming temperatures and infection may together impair host health is unclear. Using a meta-analysis of >190 effect sizes representing 101 ectothermic animal host–pathogen systems, we demonstrate that warming significantly increased the mortality of hosts infected by bacterial pathogens. Pathogens that have been evolutionarily established within the host species showed higher virulence under warmer temperatures, too. Conversely, the effect of warming on novel infections—from pathogens without a shared evolutionary history with the host species—were more pronounced with larger differences between compared temperatures. We found that compared to established infections, novel infections were more deadly at lower/baseline temperatures. Moreover, we revealed that the virulence of fungal pathogens increased only when temperatures were shifted upwards towards the pathogen thermal optimum. The magnitude of all these significant effects was not impacted by host life-stage, immune complexity, pathogen inoculation methods, or exposure time. Overall, our findings reveal distinct patterns in changes of pathogen virulence during warming. We highlight the importance of pathogen taxa, thermal optima, and evolutionary history in determining the impact of global change on infection outcomes.

A case report of Penicillium chorioretinitis in a Border Collie dog

Systemic fungal pathogens typically gain entry through a single portal and disseminate to affect multiple body systems. Infections caused by fungal Penicillium species are rare in dogs, and these cases have a poor prognosis. An unknown Penicillium species was isolated from the right eye of a middle‐aged Border Collie without evidence of systemic disease. Due to financial limitations, an extensive diagnostic evaluation could not be performed. Histopathology alone failed to identify the specific causative agent; however, fungal culture on aqueous humor provided the definitive diagnosis. This case highlights the advantage of collecting ocular fluids after enucleation to diagnose atypical fungal infections.

Aspergillus terreus IFM 65899-THP-1 cells interaction triggers production of the natural product butyrolactone Ia, an immune suppressive compound.

We focused on the possibility that pathogenic microorganisms might produce immune suppressors to evade the action of immune cells. Based on this possibility, we have recently developed new co-culture method of pathogenic actinomyces and immune cells, however, the interaction mechanism between pathogens and cells was still unclear. In this report, co-culturing pathogenic fungi and immune cells were investigated. Pathogenic fungus Aspergillus terreus IFM 65899 and THP-1 cells were co-cultured and isolated a co-culture specific compound, butyrolactone Ia (1). 1 inhibits the production of nitric oxide by RAW264 cells and exhibits regulatory effects on autophagy, suggesting 1 plays a defensive role in the response of A. terreus IFM 65899 to immune cells. Furthermore, dialysis experiments and micrographs indicated that "physical interaction" between A. terreus IFM 65899 and THP-1 cells may be required for the production of 1. This is the first report of co-culture method of fungi with immune cells and its interaction mechanism.

Evaluation of Novel Picolinamide Fungicides (QiI) for Controlling Cercospora beticola Sacc. in Sugar Beet

Studies were initiated to find new effective fungicides to use under field conditions to discover novel approaches for optimizing disease management in sugar beet crops. Cercospora leaf spot (CLS), a prevalent foliar disease in sugar beet crops worldwide, is caused by the fungal pathogen Cercospora beticola Sacc. This disease has become the most prevalent pathogen in sugar beet crops across nearly all European growing regions, including Hungary. The epidemic spread of this disease can cause up to 50% yield loss. The use of fungicides has been a cornerstone in managing CLS of sugar beet due to the limited efficacy of non-chemical alternatives. However, the emergence of fungicide-resistant strains of Cercospora beticola Sacc. in recent decades has compromised the effectiveness of certain fungicides, particularly those belonging to the QoI (FRAC Group 11) and DMI (FRAC Group 3) classes. Hungary is among the many countries where resistance to these fungicides has developed due to their frequent application. Picolinamides represent a novel class of fungal respiration inhibitors targeting Complex III within the Quinoine-Inside Inhibitor (QiI) group. Two innovative fungicides from this class, fenpicoxamid and florylpicoxamid (both classified under FRAC Group 21), were evaluated for their efficacy in managing CLS of sugar beet in Hungary during the 2020 and 2021 growing seasons. Both fungicides were applied as formulated products at various application rates and demonstrated superior efficacy in controlling CLS compared to untreated control plots and the reference fungicides difenoconazole and epoxiconazole. The results consistently demonstrated that all tested application rates of fenpicoxamid and florylpicoxamid effectively controlled CLS in sugar beet, exhibiting a clear dose–response relationship. Disease severity, as measured by the area under the disease progress curve (AUDPC), was significantly correlated with yield reduction but showed no significant association with root sugar content. Moreover, data from both study years indicated that picolinamide fungicides applied at a rate of 75 g ai/ha significantly outperformed difenoconazole (100 g ai/ha) in controlling the CLS of sugar beet. Additionally, higher application rates of picolinamides at 100–150 g ai/ha outperformed epoxiconazole at 125 g ai/ha in disease suppression. Fenpicoxamid is currently registered for use in cereals within Europe, and outside of Europe in Banana against Black Sigatoka (eff. Mycosphaerella fijiensis). Florylpicoxamid, while not yet registered in Europe, is undergoing approval processes in various countries worldwide for a range of crops and is continually being evaluated for potential market introduction. Additional details regarding the efficacy of florylpicoxamid against CLS in sugar beet were presented at ‘The 10th International Conference on Agricultural and Biological Sciences (ABS 2024, Győr-Hungary)’ in 2024.

Genome-based analysis of biosynthetic potential from antimycotic Streptomyces rochei strain A144.

Streptomyces rochei is a species of Streptomyces with a diverse range of biological activities. S. rochei strain A144 was isolated from desert soils and exhibits antagonistic activity against several plant pathogenic fungi. The genome of S. rochei A144 was sequenced and revealed the presence of one linear chromosome and one plasmid. The chromosome length was found to be 8,085,429bp, with a GC content of 72.62%, while the Plas1 length was 177,399bp, with a GC content of 69.08%. Comparative genomics was employed to analyse the S. rochei group. There is a high degree of collinearity between the genomes of S. rochei strains. Based on pan-genome analysis, S. rochei has 10,315 gene families, including 4051 core and 2322 unique genes. AntiSMASH was used to identify the gene clusters for secondary metabolites, identifying 33 secondary metabolite genes on the A144 genome. Among them, 18 clusters were found to be >70% identical to known biosynthetic gene clusters (BGCs), indicating that A144 has the potential to synthesize secondary metabolites. The majority of the BGCs were found to be conserved within the S. rochei group, including those encoding polyketide synthases (PKS), terpenes, non-ribosomal peptide synthetases (NRPS), other ribosomally synthesised and post-translationally modified peptides (RiPP), nicotianamine-iron transporters, lanthipeptides, and a few other types. The S. rochei group can be a potential genetic source of useful secondary metabolites with applications in medicine and biotechnology.

The distinctive pharmacokinetic profile of rezafungin, a long-acting echinocandin developed in the era of modern pharmacometrics.

Echinocandin drugs are the current first-line therapy for fungal infections caused by Candida spp. Most patients require once-daily intravenous (IV) administration in a hospital or outpatient setting for treatment, which may negatively impact their quality of life and stress healthcare resources. Similar to other echinocandins, the novel FDA-, EMA-, and Medical and Healthcare Products Regulatory Agency-approved echinocandin, rezafungin (CD101), exhibited strong antifungal activity against several fungal pathogens and a low drug-drug interaction liability, which are important for medically complex patients. A pharmacometric-based approach has been adopted throughout the development of rezafungin, which contrasts with older echinocandins where dosing regimens were largely derived empirically, and only recently based on pharmacometric guidance. This state-of-the-art approach used model-based simulations incorporating pre-clinical and clinical data as it became available to optimize the dosing regimen for rezafungin. The enhanced stability of the molecular structure and the safety profile of rezafungin allow for the administration of once-weekly IV doses, compared to the daily dosing requirement for other echinocandin drugs, with this distinctive pharmacokinetic profile of rezafungin resulting in a front-loaded dosing regimen with high exposures early in therapy for enhanced fungal killing. The long shelf-life of rezafungin makes this echinocandin more flexible in terms of storage and manufacturing. Demonstrated across clinical development, rezafungin may provide patients with next-generation first-line antifungal treatment for the treatment of candidaemia and invasive candidiasis.

Micro-Incubator Protocol for Testing a CO2 Sensor for Early Warning of Spontaneous Combustion

A protocol for detecting the potential occurrence of spontaneous combustion (SC) in stored cottonseeds and peanuts using a micro-incubator is described. The protocol indicates how to quantify CO2 production rates and final CO2 levels in wet versus dry cottonseed and peanut samples, which can provide crucial data for the early detection of SC risk in storage facilities. The experimental design utilizes a micro-incubator to simulate conditions found in large bulk crop storage. Parameters monitored include CO2 concentration, temperature, and relative humidity. The protocol includes preparation methods, experimental procedures for both control (dry) and wet seed tests, and test termination criteria that allow for safe experimentation of likely pathogenic fungi. The protocol has three replicates for wet and dry conditions. The protocol is intended to facilitate future experimental studies and ultimately contribute to the development of a consistently reliable early warning fire detection system for SC in cottonseed and peanut warehouse facilities. A consistently reliable fire detection system would address a critical need in the cotton and peanut industry for improved fire risk management and insurability of storage facilities.

Resistance to viral and fungal diseases in local cucurbit cultivars from the arid regions of Tunisia

Resistance to viral and fungal diseases in local cucurbit cultivars from the arid regions of Tunisia

Exploring mechanisms of gene expression control during Ustilago maydis teliospore germination

Fungal plant pathogens produce spores for survival and dispersion. Developing an understanding of the mechanisms involved in spore dormancy and germination will aid in mitigating the impact of diseases they cause. The thick-walled diploid teliospores of Ustilago maydis were used as a model for studying fungal spore dormancy and germination. These spores develop only in infected maize tissue and can remain dormant for long periods of time. Teliospores germinate under favourable conditions, resume meiosis, and produce basidiospores to initiate new rounds of infection. Previous research identified changing gene transcripts during teliospore germination, but analysis was hampered by asynchronous germination. The more comprehensive RNA-seq analysis of U. maydis teliospore germination presented here aimed to identify gene altered transcript levels detectable above the background of fluctuating changes resulting from asynchronous germination. The analyses identified 18 different patterns of gene transcript level changes. It also indicated that gene expression is controlled at the transcriptional and post-transcriptional levels. Gene ontology term enrichment analyses of these patterns revealed genes that are involved in cell morphogenesis, metabolism, and RNA metabolism.

A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogen Candida glabrata.

Drug-resistant microbes typically carry mutations in genes involved in critical cellular functions and may therefore be less fit under drug-free conditions than susceptible strains. Candida glabrata is a prevalent opportunistic yeast pathogen with a high rate of fluconazole resistance (FLZR), echinocandin resistance (ECR), and multidrug resistance (MDR) relative to other Candida. However, the fitness of C. glabrata MDR isolates, particularly in the host, is poorly characterized, and studies of FLZR isolate fitness have produced contradictory findings. Two important host niches for C. glabrata are macrophages, in which it survives and proliferates, and the gut. Herein we used a collection of clinical and lab-derived C. glabrata isolates to show that FLZR C. glabrata isolates are less fit inside macrophages than susceptible isolates and that this fitness cost is reversed by acquiring ECR mutations. Interestingly, dual-RNAseq revealed that macrophages infected with drug-resistant isolates mount an inflammatory response whereas intracellular drug-resistant cells downregulate processes required for in-host adaptation. Furthermore, drug-resistant isolates were outcompeted by their susceptible counterparts during gut colonization and in infected kidneys, while showing comparable fitness in the spleen. Collectively, our study shows that macrophage-rich organs, such as the spleen, favor the retention of MDR isolates of C. glabrata.

Reintroduction of resistant frogs facilitates landscape-scale recovery in the presence of a lethal fungal disease.

Vast alteration of the biosphere by humans is causing a sixth mass extinction, driven in part by an increase in infectious diseases. The emergence of the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd) has devastated global amphibian biodiversity. Given the lack of any broadly applicable methods to reverse these impacts, the future of many amphibians appears grim. The Sierra Nevada yellow-legged frog (Rana sierrae) is highly susceptible to Bd infection and most R. sierrae populations are extirpated following disease outbreaks. However, some populations persist and eventually recover, and frogs in these recovering populations have increased resistance against infection. Here, we conduct a 15-year reintroduction study and show that frogs collected from recovering populations and reintroduced to vacant habitats can reestablish populations despite the presence of Bd. In addition, the likelihood of establishment is influenced by site, cohort, and frog attributes. Results from viability modeling suggest that many reintroduced populations have a low probability of extinction over 50 years. These results provide a rare example of how reintroduction of resistant individuals can allow the landscape-scale recovery of disease-impacted species, and have broad implications for amphibians and other taxa that are threatened with extinction by novel pathogens.

Genome-wide association of an organic naked barley diversity panel identified quantitative trait loci for disease resistance.

Foliar fungal diseases are a major limitation in organic naked barley (Hordeum vulgare L.) production. The lack of conventional fungicides in organic systems increases reliance on genetic resistance. We evaluated the severity of barley stripe rust (Puccinia striiformis f.sp. hordei Westend), leaf rust (Puccina hordei sp. hordei), spot blotch (Cochliobolus sativus, anamorph Bipolaris sorokiniana (S. Ito & Kurib.) Drechsler ex Dastur), and scald (Rhynchosporium commune Zaffarano, McDonald and Linde sp. November) on a naked barley diversity panel of 350 genotypes grown in 13 environments to identify quantitative trait loci associated with disease resistance. Genome-wide association analyses across and within environments found 10 marker trait associations for barley stripe rust, four marker trait associations for leaf rust, one marker trait association for scald, and five marker trait associations for spot blotch. Structure analysis identified six Ward groups based on genotypic diversity. Resistance to susceptible allele ratios were high for stripe rust and spot blotch, moderate for leaf rust, and low for scald. Combined phenotypic analysis values for each disease overlayed by a principal component analysis found distinct resistance and susceptibility patterns for barley stripe rust and scald. Most significant marker trait associations were previously identified in the literature, providing confirmation and potential new sources of disease resistance for genetic improvement of naked barley germplasm.

Safety, outcomes, and pharmacokinetics of isavuconazole as a treatment for invasive fungal diseases in pediatric patients: a non-comparative phase 2 trial.

Invasive aspergillosis (IA) and mucormycosis (IM) cause significant morbidity and mortality in immunocompromised and/or hospitalized patients. Isavuconazonium sulfate, a prodrug of the antifungal triazole isavuconazole, has been approved for treatment of IA and IM in adults; and was recently approved in children. This study describes the outcomes, safety, and pharmacokinetics of isavuconazole for the treatment of proven, probable, or possible IA or IM in children. In this phase 2, open-label, non-comparative study, patients aged 1 to <18 years with at least possible invasive mold disease were enrolled across 10 centers in the US, Spain, and Belgium from 2019 to 2022. Patients received 10 mg/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg/kg or 200 mg isavuconazole) for up to 84 (IA) or 180 days (IM). Outcomes included rates of all-cause case fatality, overall response, treatment-emergent adverse events (TEAEs), and pharmacokinetics. Of 31 patients enrolled, 61.3% were 1-<12 years old; 58.1% had underlying hematologic malignancies. The successful overall response rate at the end of treatment was 54.8%. Day 42 all-cause case fatality was 6.5%; 93.5% experienced TEAEs, and two patients discontinued treatment due to drug-related TEAEs. Dosing at 10 mg/kg (maximum dose: 372 mg) met the pre-defined exposure threshold of above the 25th percentile for the area under the concentration-time curve (≥60 mg·h/L). Simulated doses of 15 mg/kg improved drug exposures in patients aged 1-<3 years. Isavuconazole was well tolerated in children, with exposure consistent with adult studies. Successful response was documented in 54.8% of patients.CLINICAL TRIALSThis study is registered at ClinicalTrials.gov as NCT03816176.

Antifungal Activity of Novel Isoindoline-2-Yl Putrescines as Potential Autophagy-Activated Fungicide.

The exacerbation of plant fungal diseases necessitates the development of new fungicides to prevent outbreaks. In this study, five novel isoindoline-2-yl putrescines (ISPs) were synthesized, and their synthetic procedures and gram-scale preparation were explored. When tested at 50 μg mL-1, ISPs did not significantly inhibit mycelial growth on agar plates. However, at 100 μg mL-1, they demonstrated remarkable in vivo efficacy in mitigating Botrytis cinerea infection, especially ISP3 showed curative and protective activities of 91.9 % and 92.6 %, respectively. Moreover, ISP3 also effectively halted lesion expansion of gray mold, Sclerotic rot, and Fusarium scabs, while inducing excessive malformed top mycelial branches of B. cinerea and Sclerotinia sclerotiorum, suppressing sclerotia formation in S. sclerotiorum, and triggering autophagic vacuolization with numerous autophagosomes in the mycelia of these fungi. Molecular docking revealed that ISP3 effectively bound to the active site of BcAtg3, forming hydrogen bonds with Ser279, Gly343, Asp370, and Asp13, along with establishing a stable salt bridge with Asp13. Furthermore, ISP3 possessed favorable ADMET properties. These findings highlight ISP3 as a promising antifungal candidate through autophagy activation.

Isolation and identification of antifungal, antibacterial and nematocide agents from marine bacillus gottheilii MSB1.

Pathogenic fungi employ numerous strategies to colonize plants, infect them, reduce crop yield and quality, and cause significant losses in agricultural production. The increasing use of chemical pesticides has led to various ecological and environmental issues, including the emergence of resistant weeds, soil compaction, and water pollution, all negatively impacting agricultural sustainability. Additionally, the extensive development of synthetic fungicides has adverse effects on animal and human health, prompting the exploration of alternative approaches and green strategies for phytopathogen control. Microorganisms living in sponges represent a promising source of novel bioactive secondary metabolites, potentially useful in developing new nematicidal and antimicrobial agents. This study focuses on extracting bioactive compounds from endosymbiotic bacteria associated with the marine sponge Hyrtios erect sp. (collected from NIOF Station, Hurghada, Red Sea, Egypt) using various organic solvents. Bacillus sp. was isolated and identified through 16S rRNA gene sequencing. The biocidal activity of Bacillus gotheilii MSB1 extracts was screened against plant pathogenic bacteria, fungi, and nematodes. The n-butanol extract showed significant potential as a biological fungicide against Alternaria alternata and Fusarium oxysporum. Both n-hexane and ethyl acetate extracts exhibited negative impacts against the plant pathogenic bacteria Erwinia carotovora and Ralstonia solanacearum, whereas the n-butanol extract had a positive effect. Regarding nematicidal activity, ethyl acetate and n-butanol extracts demonstrated in-vitro activity against the root-knot nematode Meloidogyne incognita, which causes serious vegetable crop diseases, but the n-hexane extract showed no positive effects. The findings suggest that bioactive compounds from endosymbiotic bacteria associated with marine sponges, particularly B. gotheilii MSB1, hold significant potential as alternative biological control agents against plant pathogens. The n-butanol extract, in particular, displayed promising biocidal activities against various plant pathogenic fungi, bacteria, and nematodes. These results support further exploration and development of such bioactive compounds as sustainable, environmentally friendly alternatives to synthetic pesticides and fungicides in agricultural practices.

DESEMPENHO DA PRODUTIVIDADE DE MILHO A PARTIR DE APLICAÇÃO DE FUNGICIDA EM DIFERENTES ESTÁGIOS FENOLÓGICOS

Corn (Zea mays L.) is a crucial crop in terms of global production and economic value, but it is susceptible to fungal diseases such as common rust (Puccinia sorghi) and cercosporiosis (Cercospora zeae-maydis), which can reduce grain production and quality. Effective control of these diseases is vital for food security and agricultural economy. Proper management of corn fungal diseases depends on the plant's phenological stages, from planting to grain maturity. The application of fungicides at strategic moments during the plant's life cycle is essential to prevent infections and reduce disease impact. A study conducted in Patos de Minas, Minas Gerais, during 2023, evaluated the effect of fungicide application at different phenological stages of corn on final productivity. The results showed that fungicide application at multiple phenological stages (V4, V8, and VT) resulted in greater above-ground height, lower severity of fungal diseases, higher productivity, and uniform stalk diameter compared to the control treatment. This integrated disease management method proved effective in protecting plants against fungal diseases, promoting healthier and more vigorous growth, and increasing final corn productivity. These findings highlight the importance of fungicide application at strategic moments in the corn development cycle to maximize productivity and promote more efficient and sustainable agriculture.

Frequent genetic exchanges revealed by a pan-mitogenome graph of a fungal plant pathogen.

Mitochondria are present in almost all eukaryotic lineages. The mitochondrial genomes (mitogenomes) evolve separately from nuclear genomes, and they can therefore provide relevant insights into the evolution of their host species. Fusarium oxysporum is a major fungal plant pathogen that is assumed to reproduce clonally. However, horizontal chromosome transfer between strains can occur through heterokaryon formation, and recently, signs of sexual recombination have been observed. Similarly, signs of recombination in F. oxysporum mitogenomes challenged the prevailing assumption of clonal reproduction in this species. Here, we construct, to our knowledge, the first fungal pan-mitogenome graph of nearly 500 F. oxysporum mitogenome assemblies to uncover the variation and evolution. In general, the gene order of fungal mitogenomes is not well conserved, yet the mitogenome of F. oxysporum and related species are highly colinear. We observed two strikingly contrasting regions in the F. oxysporum pan-mitogenome, comprising a highly conserved core mitogenome and a long variable region (6-16 kb in size), of which we identified three distinct types. The pan-mitogenome graph reveals that only five intron insertions occurred in the core mitogenome and that the long variable regions drive the difference between mitogenomes. Moreover, we observed that their evolution is neither concurrent with the core mitogenome nor with the nuclear genome. Our large-scale analysis of long variable regions uncovers frequent recombination between mitogenomes, even between strains that belong to different taxonomic clades. This challenges the common assumption of incompatibility between genetically diverse F. oxysporum strains and provides new insights into the evolution of this fungal species.IMPORTANCEInsights into plant pathogen evolution is essential for the understanding and management of disease. Fusarium oxysporum is a major fungal pathogen that can infect many economically important crops. Pathogenicity can be transferred between strains by the horizontal transfer of pathogenicity chromosomes. The fungus has been thought to evolve clonally, yet recent evidence suggests active sexual recombination between related isolates, which could at least partially explain the horizontal transfer of pathogenicity chromosomes. By constructing a pan-genome graph of nearly 500 mitochondrial genomes, we describe the genetic variation of mitochondria in unprecedented detail and demonstrate frequent mitochondrial recombination. Importantly, recombination can occur between genetically diverse isolates from distinct taxonomic clades and thus can shed light on genetic exchange between fungal strains.

Single-cell transcriptomics unveils skin cell specific antifungal immune responses and IL-1Ra- IL-1R immune evasion strategies of emerging fungal pathogen Candida auris.

Candida auris is an emerging multidrug-resistant fungal pathogen that preferentially colonizes and persists in skin tissue, yet the host immune factors that regulate the skin colonization of C. auris in vivo are unknown. In this study, we employed unbiased single-cell transcriptomics of murine skin infected with C. auris to understand the cell type-specific immune response to C. auris. C. auris skin infection results in the accumulation of immune cells such as neutrophils, inflammatory monocytes, macrophages, dendritic cells, T cells, and NK cells at the site of infection. We identified fibroblasts as a major non-immune cell accumulated in the C. auris infected skin tissue. The comprehensive single-cell profiling revealed the transcriptomic signatures in cytokines, chemokines, host receptors (TLRs, C-type lectin receptors, NOD receptors), antimicrobial peptides, and immune signaling pathways in individual immune and non-immune cells during C. auris skin infection. Our analysis revealed that C. auris infection upregulates the expression of the IL-1RN gene (encoding IL-1R antagonist protein) in different cell types. We found IL-1Ra produced by macrophages during C. auris skin infection decreases the killing activity of neutrophils. Furthermore, C. auris uses a unique cell wall mannan outer layer to evade IL-1R-signaling mediated host defense. Collectively, our single-cell RNA seq profiling identified the transcriptomic signatures in immune and non-immune cells during C. auris skin infection. Our results demonstrate the IL-1Ra and IL-1R-mediated immune evasion mechanisms employed by C. auris to persist in the skin. These results enhance our understanding of host defense and immune evasion mechanisms during C. auris skin infection and identify potential targets for novel antifungal therapeutics.

Characteristics of soil microbial community assembly patterns in fields with serious occurrence of tobacco Fusarium wilt disease

IntroductionFusarium wilt disease (FWD) of tobacco is a destructive disease caused by Fusarium spp. in tobacco-growing regions worldwide. The Fusarium spp. infection may alter the composition and structure of the tobacco root microbial community; however, the relationship between these factors under large-scale geographical conditions in China remains underexplored.MethodsIn the context of this investigation, soil samples from the rhizosphere of tobacco plants were procured from fields afflicted with FWD and those devoid of the disease in the Hanzhong region of Shaanxi province, as well as in the Sanmenxia and Nanyang regions of Henan province. These regions are recognized for the commercial cultivation of tobacco. The examination focused on discerning the influence of tobacco FWD on the composition and configuration of the rhizosphere microbial community, along with their co-occurrence patterns. This scrutiny was underpinned by targeted PCR amplification and high-throughput sequencing (amplicon sequencing) of the 16S rRNA gene and the ITS1 region.ResultsThe amplicon data analyses showed that FWD influenced the microbial structure and composition of the tobacco rhizosphere soil. FWD had a greater impact on the microbiome of the tobacco fungal community than on the microbiome of the bacterial community. Healthy plants had the ability to recruit potential beneficial bacteria. Diseased plants were more susceptible to colonization by other pathogenic fungi, but they still had the capacity to recruit potential beneficial bacteria. The analysis of microbial intra- and inter-kingdom networks further indicated that FWD destabilized microbial networks. In the overall microbial interaction, microorganisms primarily interacted within their boundaries, but FWD increased the proportion of interactions occurring across boundaries. In addition, FWD could disrupt the interactions within microbial network modules.DiscussionThis study provides evidence that FWD can cause changes in the composition and network of microbial communities, affecting the interactions among various microorganisms, including bacteria and fungi. These findings contribute to our understanding of how plant microbiomes change due to disease. Furthermore, they add to our knowledge of the mechanisms that govern the assembly and interactions of microbial communities under the influence of FWD.