Management Of Fungal Diseases Research Articles

Identification and delineation of action mechanism of antifungal agents: Reveromycin E and its new derivative isolated from Streptomyces sp. JCK-6141

Streptomyces species have been used as biocontrol agents for the management of fungal postharvest diseases. Reveromycin E (RE) and its new derivative, reveromycin E 1-methyl ester (REME), were isolated from Streptomyces sp. JCK-6141. Both compounds displayed broad-spectrum and extensive antifungal activities at acidic condition, but their activities were dramatically reduced at neutral or base conditions. These compounds effectively suppressed the cherry tomato gray mold and mandarin blue mold caused by Botrytis cinerea and Penicillium italicum, respectively, at 10 and 50 mg L−1. In in vitro and in vivo assays, RE showed stronger antifungal activity than REME. Reveromycin was known as an isoleucine tRNA synthetase (IleRS) inhibitor. However, there is unconsolidated result in confirming binding site of reveromycin in previous studies. A computational study revealed that RE had a lower binding energy than REME and both compounds tend to bind catalytic domain rather than editing domains of IleRS. Our results indicated that Streptomyces sp. JCK-6141 producing reveromycins can be widely used as a new microbial fungicide for the control of postharvest diseases on fruit.

Nanoarchitectures in Management of Fungal Diseases: An Overview

Fungal infections, from mild itching to fatal infections, lead to chronic diseases and death. Antifungal agents have incorporated chemical compounds and natural products/phytoconstituents in the management of fungal diseases. In contrast to antibacterial research, novel antifungal drugs have progressed more swiftly because of their mild existence and negligible resistance of infections to antifungal bioactivities. Nanotechnology-based carriers have gained much attention due to their magnificent abilities. Nanoarchitectures have served as excellent carriers/drug delivery systems (DDS) for delivering antifungal drugs with improved antifungal activities, bioavailability, targeted action, and reduced cytotoxicity. This review outlines the different fungal diseases and their treatment strategies involving various nanocarrier-based techniques such as liposomes, transfersomes, ethosomes, transethosomes, niosomes, spanlastics, dendrimers, polymeric nanoparticles, polymer nanocomposites, metallic nanoparticles, carbon nanomaterials, and nanoemulsions, among other nanotechnological approaches.

Calcium and Silicon Fertiliser Influence on Fungicide Efficacy Against Guignardia Leaf Blotch and Apple Scab Management

Management of fungal diseases within urban landscapes relies heavily on repeat fungicide sprays. Environmental concerns have led to a need to eliminate or reduce fungicide use. Foliar sprays of calcium- (Ca) and silicon- (Si) based fertilisers have been shown to reduce symptom severity of several fungal pathogens. The aim of our research was to evaluate the influence of Ca chloride, Ca metasolate, tetra ethyl silicate, and potassium silicate fertilisers, applied independently and in combination with a synthetic fungicide (penconazole) at full and half strength, on apple scab (Venturia inaequalis) and Guignardia leaf blotch (Guignardia aesculi) symptom severity, as well as leaf chlorophyll content, fruit yield, and crown volume. Trials used container-grown Aesculus hippocastanum and field-grown Malus domestica cv. ‘Golden Delicious’. Applications of Ca, Si, and penconazole sprays alone significantly reduced scab and leaf blotch severity compared to water-sprayed controls; however, a significant difference between the type of Ca and Si fertilisers was recorded. A combined mix of a Ca or Si fertiliser with a full or half dose of penconazole was more effective at reducing symptom severity of both foliar pathogens than a full or half dose of penconazole alone. Data analysed with Limpel’s formula indicated positive synergistic effects between Ca and Si and penconazole in some, but not all, cases. The integration of Ca and Si foliar sprays as an alternative to, or additive with, penconazole for scab and leaf blotch management appears feasible based on results of our studies and may have applicability against other fungal pathogens.

Differential Physiological Prerequisites and Gene Expression Profiles of Conidial Anastomosis Tube and Germ Tube Formation in Colletotrichum gloeosporioides

The conidia of a hemibiotrophic fungus, Colletotrichum gloeosporioides, can conventionally form a germ tube (GT) and develop into a fungal colony. Under certain conditions, they tend to get connected through a conidial anastomosis tube (CAT) to share the nutrients. CAT fusion is believed to be responsible for the generation of genetic variations in few asexual fungi, which appears problematic for effective fungal disease management. The physiological and molecular requirements underlying the GT formation versus CAT fusion remained underexplored. In the present study, we have deciphered the physiological prerequisites for GT formation versus CAT fusion in C. gloeosporioides. GT formation occurred at a high frequency in the presence of nutrients, while CAT fusion was found to be higher in the absence of nutrients. Younger conidia were found to form GT efficiently, while older conidia preferentially formed CAT. Whole transcriptome analysis of GT and CAT revealed highly differential gene expression profiles, wherein 11,050 and 9786 genes were differentially expressed during GT formation and CAT fusion, respectively. A total of 1567 effector candidates were identified; out of them, 102 and 100 were uniquely expressed during GT formation and CAT fusion, respectively. Genes coding for cell wall degrading enzymes, germination, hyphal growth, host-fungus interaction, and virulence were highly upregulated during GT formation. Meanwhile, genes involved in stress response, cell wall remodeling, membrane transport, cytoskeleton, cell cycle, and cell rescue were highly upregulated during CAT fusion. To conclude, the GT formation and CAT fusion were found to be mutually exclusive processes, requiring differential physiological conditions and sets of DEGs in C. gloeosporioides. This study will help in understanding the basic CAT biology in emerging fungal model species of the genus Colletotrichum.

Outstanding Contributions of LAL Technology to Pharmaceutical and Medical Science: Review of Methods, Progress, Challenges, and Future Perspectives in Early Detection and Management of Bacterial Infections and Invasive Fungal Diseases.

The blue blood of the horseshoe crab is a natural, irreplaceable, and precious resource that is highly valued by the biomedical industry. The Limulus amebocyte lysate (LAL) obtained from horseshoe crab blood cells functions as a surprisingly sophisticated sensing system that allows for the extremely sensitive detection of bacterial and fungal cell-wall components. Notably, LAL tests have markedly contributed to the quality control of pharmaceutical drugs and medical devices as successful alternatives to the rabbit pyrogen test. Furthermore, LAL-based endotoxin and (1→3)-β-D-glucan (β-glucan) assay techniques are expected to have optimal use as effective biomarkers, serving as adjuncts in the diagnosis of bacterial sepsis and fungal infections. The innovative β-glucan assay has substantially contributed to the early diagnosis and management of invasive fungal diseases; however, the clinical significance of the endotoxin assay remains unclear and is challenging to elucidate. Many obstacles need to be overcome to enhance the analytical sensitivity and clinical performance of the LAL assay in detecting circulating levels of endotoxin in human blood. Additionally, there are complex interactions between endotoxin molecules and blood components that are attributable to the unique physicochemical properties of lipopolysaccharide (LPS). In this regard, while exploring the potential of new LPS-sensing technologies, a novel platform for the ultrasensitive detection of blood endotoxin will enable a reappraisal of the LAL assay for the highly sensitive and reliable detection of endotoxemia.

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease.

Allergy to airway-colonising, thermotolerant, filamentous fungi represents a distinct eosinophilic endotype of often severe lung disease. This endotype, which particularly affects adult asthma, but also complicates other airway diseases and sometimes occurs de novo, has a heterogeneous presentation ranging from severe eosinophilic asthma to lobar collapse. Its hallmark is lung damage, characterised by fixed airflow obstruction (FAO), bronchiectasis and lung fibrosis. It has a number of monikers including severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis/mycosis (ABPA/M), but these exclusive terms constitute only sub-sets of the condition. In order to capture the full extent of the syndrome we prefer the inclusive term allergic fungal airway disease (AFAD), the criteria for which are IgE sensitisation to relevant fungi in association with airway disease. The primary fungus involved is Aspergillus fumigatus, but a number of other thermotolerant species from several genera have been implicated. The unifying mechanism involves germination of inhaled fungal spores in the lung in the context of IgE sensitisation, leading to a persistent and vigorous eosinophilic inflammatory response in association with release of fungal proteases. Most allergenic fungi, including Alternaria and Cladosporium species, are not thermotolerant and cannot germinate in the airways so only act as aeroallergens and do not cause AFAD. Studies of the airway mycobiome have shown that A. fumigatus colonises the normal as much as the asthmatic airway, suggesting it is the tendency to become IgE-sensitised that is the critical triggering factor for AFAD rather than colonisation per se. Treatment is aimed at preventing exacerbations with glucocorticoids and increasingly by the use of anti-T2 biological therapies. Anti-fungal therapy has a limited place in management, but is an effective treatment for fungal bronchitis which complicates AFAD in about 10% of cases.

Mortality Trends in Risk Conditions and Invasive Mycotic Disease in the United States, 1999-2018.

Invasive fungal infections in the United States are chronically underdiagnosed and a lack of coordinated surveillance makes the true burden of disease difficult to determine. The purpose of this analysis was to capture mortality-associated burden of risk conditions and fungal infections. We analyzed data from the National Vital Statistics System from 1999 through 2018 to estimate the mortality attributed to risk conditions and related fungal disease. The number of risk conditions associated with fungal disease is steadily rising in the United States, with 1 047 422 diagnoses at time of death in 2018. While fungal disease decreased substantially from 1999 to 2010, primarily due to the control of human immunodeficiency virus (HIV) infection, the number of deaths with fungal diagnosis has increased in the non-HIV cohort, with significant increases in patients with diabetes, cancer, immunosuppressive disorders, or sepsis. The landscape of individuals at risk for serious fungal diseases is changing, with a continued decline in HIV-associated incidence but increased diagnoses in patients with cancer, sepsis, immunosuppressive disorders, and influenza. Additionally, there is an overall increase in the number of fungal infections in recent years, indicating a failure to control fungal disease mortality in these new immunocompromised cohorts. Improvement in the prevention and management of fungal diseases is needed to control morbidity and mortality in the rising number of immunocompromised and at-risk patients in the United States.

8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation.

Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.

Genetics of resistance to rust and powdery mildew in linseed (Linum usitatissimum L.)

Linseed is an important oilseed crop. It is infected by a number of fungal, bacterial, nematode and viral diseases. Among the 12 fungal diseases infecting the crop, rust (Melampsora lini) and powdery mildew (Oidium lini) are the major diseases causing severe yield losses. Development of resistant varieties is efficacious, economical, durable and safe approach for the management of fungal diseases on linseed. In this context, studies were conducted for investigating the inheritance of resistance to rust and powdery mildew in linseed under field conditions at the prominent hot spot locations i.e., Kangra and Palampur. Inheritance of rust resistance was studied using six generations derived from hybridization between three diverse genotypes i.e. T-397 (susceptible), Nagarkot and Baner (resistant), were evaluated at SAREC, Kangra whereas, inheritance of powdery mildew was studied at Palampur involving varieties T-397 (susceptible) and Nagarkot (resistant). In cross combinations T-397 × Nagarkot and T-397 × Baner, F2 generations were segregated in the ratio 3(R):1(S) indicating the monogenic inheritance of rust resistance. In case of powdery mildew, cross combination T-397 × Nagarkot was tested and F2 generation segregated in the ratio 3(R):1(S) as well. The results obtained from the study indicated that single dominant gene controlled both rust and powdery mildew resistance.

Biocontrol potential and mode of action of entomopathogenic bacteria Xenorhabdus budapestensis C72 against Bipolaris maydis

Southern corn leaf blight (SCLB) caused by Bipolaris maydis is an important foliar disease of maize. In this study, a nematode-symbiotic bacterium Xenorhabdus budapestensis strain C72 was identified with remarkable inhibiting effect on mycelial growth and spore germination of B. maydis. The in vitro assay revealed that C72 cell-free culture media (CFCM) with thermostability exhibited broad-spectrum antifungal activities against other several important plant pathogenic fungi. The early colonization of B. maydis were significantly impaired by CFCM treatment under phytotron condition. This antagonism is likely to be the main contributor to the highly efficient plant protection of 40% (v/v) CFCM treatment against B. maydis, and the relative control effect reached to 59.15% and 77.96% in greenhouse and field experiments, which was comparable to the effect of fungicides. Moreover, we found that extracellular enzymes secreted by symbiotic bacterium may be one of the reasons for the antifungal potential of C72. Beside direct antagonistic effects provided by the bacterium, defense related genes were induced in maize after CFCM treatment. In summary, this study reported the first systematic evaluation of the effect of X. budapestensis C72 in controlling SCLB and exploration of its mode of action, then indicating that entomopathogenic bacteria have the potential to become a new and efficient biological control resource for plant fungal disease management.

Characterization of Aspergillus fumigatus cross-resistance between clinical and DMI azole drugs.

Drug resistance poses a serious threat to human health and agricultural production. Azole drugs are the largest group of 14-α sterol demethylation inhibitor fungicides that are used both in agriculture and in clinical practice. As plant pathogenic molds share their natural environment with fungi that cause opportunistic infections in humans, both are exposed to a strong and persistent pressure of demethylase inhibitor (DMI) fungicides, including imidazole and triazole drugs. As a result, a loss of efficacy has occurred for this drug class in several species. In the clinical setting, Aspergillus fumigatus azole resistance is a growing public health problem and finding the source of this resistance has gained much attention. It is urgent to determine if there is a direct link between the agricultural use of azole compounds and the different A. fumigatus resistance mechanisms described for clinical triazoles. In this work we have performed A. fumigatus susceptibility testing to clinical triazoles and crop protection DMIs using a collection of azole susceptible and resistant strains which harbor most of the described azole resistance mechanisms. Various DMI susceptibility profiles have been found in the different A. fumigatus populations groups based on their azole resistance mechanism and previous WGS analysis, which suggests that the different resistance mechanisms have different origins and are specifically associated to the local use of a particular DMI.Importance Due to the worldwide emergence of A. fumigatus azole resistance, this opportunistic pathogen poses a serious health threat and, therefore, it has been included in the Watch List of the CDC 2019 Antimicrobial Resistance Threats Report. Azoles play a critical role in the control and management of fungal diseases, not only in the clinical setting but also in agriculture. Thus, azole resistance leads to a limited therapeutic arsenal which reduces the treatment options for aspergillosis patients, increasing their mortality risk. Evidence is needed to understand whether A. fumigatus azole resistance is emerging from an agricultural source due to the extended use of demethylase inhibitors as fungicides, or whether it is coming from somewhere else such as the clinical setting. If the environmental route is demonstrated, the current use and management of azole antifungal compounds might be forced to change in the forthcoming years.

Nanohybrid Antifungals for Control of Plant Diseases: Current Status and Future Perspectives.

The changing climatic conditions have led to the concurrent emergence of virulent microbial pathogens that attack crop plants and exhibit yield and quality deterring impacts on the affected crop. To counteract, the widespread infections of fungal pathogens and post-harvest diseases it is highly warranted to develop sustainable techniques and tools bypassing traditional agriculture practices. Nanotechnology offers a solution to the problems in disease management in a simple lucid way. These technologies are revolutionizing the scientific/industrial sectors. Likewise, in agriculture, the nano-based tools are of great promise particularly for the development of potent formulations ensuring proper delivery of agrochemicals, nutrients, pesticides/insecticides, and even growth regulators for enhanced use efficiency. The development of novel nanocomposites for improved management of fungal diseases can mitigate the emergence of resilient and persistent fungal pathogens and the loss of crop produce due to diseases they cause. Therefore, in this review, we collectively manifest the role of nanocomposites for the management of fungal diseases.

PLANT BIOACTIVE CHEMICALS FOR ANTI-FUNGAL AND BIOFUNGICIDAL POTENCIES: A REVIEW

Fungi are the major infectious agents of plant diseases causing significant economic loses to farmers and nations alike. These plant fungal diseases are mostly treated with synthetic chemicals. However, indiscriminate use of these chemicals has increased fungi resistance in plants; constitute residues in plants, their fruits and the environment, and consequently has negative impact on the health of consumers as well as the eco-system. This has led to the drive to search for plant bioactive chemicals which are biodegradable and eco-friendly. Organic products have been researched for use as safe alternative to the use of synthetic chemicals for use and management of plant diseases. The products are not harmful to the health of man and his environment. This paper reviews the bioactive compounds of plants for anti-fungal and bio-fungicidal potencies for plant disease management and the mode of actions of these compounds. From the findings of this study, there are myriads of plant species with bioactive chemicals. This review also revealed that the bioactive compounds are capable of depleting the metals of the pathogens; make them loose their membrane integrity; compete with the fungal pathogen’s steroids to inhibit their spore germinations; cause damage to the fungal plasma membrane, DNA and cytoplasmic granulation, disrupt plasma membrane and leakage of cellular contents. The bioactive compounds also inhibit fungal ATpases, resulting to the dissolution of fungal chaperones and co- chaperones which are the second proteins of fungal cytoskeleton. The mode of actions of the bioactive chemicals show they are effective, without any destructive impact on the consumer and the ecosystem. Based on the findings in this review, the use of plant organic chemicals is recommended as sustainable alternative for the management of plant fungal diseases.

Trichoderma based biological management of major fungal diseases in pulse crops

Pulses are an integral part of Indian agriculture due to their multiple utility in human food, animal feed and soil health. India has the distinction of being the top producer of pulses in the world. About 8–10% grain yield of pulse crops are annually lost due to various diseases. Majority of the fungal diseases are soil and seed borne in nature therefore, difficult to manage by conventional management practices consisting of growing resistant cultivars and use of fungicides. Among the various types of biological control agents, Trichoderma species have been extensively exploited. They were found to be effective against large number of soil, seed and air borne fungal plant pathogens. The ideal characteristic features like high reproductive capacity, rhizosphere modification ability, survival ability under adverse conditions, nutrients utilization efficiency, aggressiveness against plant pathogens and promoting plant growth and defense mechanism makes Trichoderma as a successful biocontrol agent. Seed and soil application bio-formulations were developed from different potential species of Trichoderma to increase shelf life and efficacy. Pusa 5SD a seed dressing formulation and Pusa Biopellet (PBP) a soil application formulation showed longer shelf life. The efficacies of newly developed bio-formulations were evaluated in pot and filed experiments against several diseases of pulse crops namely, dry (Rhizoctonia bataticola) and wet root rot (R. solani) of mungbean and ckickpea, wilt (Fusarium oxysporum f. sp. ciceris) of chickpea and root rot (Rhizoctonia solani) and damping off (Pythium ultimum) complex in French bean. T. harzianum based formulations were found superior over others against R. bataticola and Fusarium species whereas, T. virens based formulations were found superior against R. solani. A combined application of PBP 10G (T. harzianum) in soil and Pusa 5SD + carboxin as seed treatment showed superiority over any other formulations alone in reducing the dry root rot incidence and increasing grain yield of mungbean and chickpea. Soil application of PBP 4G (T. viride) and seed treatment with Pusa 5SD (T. harzianum) + carboxin provided the highest yield attributing parameters with the lowest wilt incidence in chickpea. T. virens based Pusa 5SD and PBG 6 were found effective in reducing wet root rot and increasing yield in mungbean and chickpea. Seed treatment proved superiority over soil application for all the parameters recorded. Both the formulations (soil and seed treatment) showed growth promoting ability. During validation, Pusa 5SD (T. harzianum) alone and in combination with Vitavax power (carboxin + thiram) reduced the wilt incidence and enhanced the grain yield of chickpea at 8 different locations across the country. French bean seeds treated with T. harzianum based Pusa 5 SD + P. fluorescens provided the highest seed germination, root and shoot lengths, dry plant weight, pod yield and the lowest disease incidence. Further, combined application of Pusa 5SD (T. harzianum), PGPR strain P. fluorescens, M. ciceri and Vitavax power as seed treatment gave extreme protection to germinating chickpea plants with the highest grain yield and the lowest wilt incidence.

Design and development of terbinafine hydrochloride ethosomal gel for enhancement of transdermal delivery: In vitro, in vivo, molecular docking, and stability study

Terbinafine HCl (TH), an allylamine antifungal (BCS-II) drug has poor solubility and high permeability. In the present work, we have investigated the potential of ethosomes as vesicular lipid nanocarrier for enhancement of transdermal application of TH. The ethosomal formulation with varying concentrations of phospholipon 80H (PL80H) and the hydroethanolic solution was optimized and fabricated by applying a 32 full factorial design. The impact of independent variables PL80H (X1) and hydroethanolic solution (X2) on dependent variables viz., vesicle size (nm), zeta potential (mV), and entrapment efficiency (EE%) were studied. The formulation batch F8 with 100 mg phospholipon 80H (PL80H) and 40% w/v hydroethanolic was considered as most optimized amongst all the batches. The optimized TH ethosomes were embedded into 1% w/v Carbopol 934 gel to study drug release and skin interaction studies. The optimized formulation evidenced with vesicle size 127.39 ± 2.71 nm, zeta potential - 40.63 ± 2.77 mV and entrapment efficiency 87.55 ± 0.47%. The drug release from optimized ethosomal suspension through the cellophane membrane was much better sustained over 24 h compared to the marketed product. Additionally, the zone of inhibition of ethosomal gel against Aspergillus Bravia (fungal strain) was larger than the marketed product. We have also investigated the inhibitory potential of Terbinafine against squalene epoxidase of Aspergillus through molecular docking. The binding interactions have shown favorable results and explained the role of Terbinafine in fungus growth inhibition. The present study demonstrates that ethosomal vesicle has the potential to enhance transdermal delivery without any skin irritation. The TH loaded ethosomes could be one of the prominent approaches for transdermal application in the management of fungal diseases.

Implementation of Effective Antifungal Stewardship in Cancer Patients—A Review of Current Evidence

This review summarizes the literature around antifungal stewardship (AFS) with a focus on the cancer setting. We include a review of identified challenges to the implementation of AFS, summarize studies evaluating quality of prescribing and interventions to optimize invasive fungal disease management. We also provide a review of metrics for AFS programs and advances in fungal diagnostics which can be harnessed by the AFS team. In recent times, there has been an increase in targeted research assessing the quality of antifungal prescribing and the impact of AFS interventions, largely within single centers and observational in nature. Several challenges exist to the implementation of AFS programs. Studies have found high rates of suboptimal antifungal prescribing, and multifaceted interventions have been successful in optimizing the quality and reducing the volume of prescribing. Standardized metrics may assist hospitals to interpret data effectively and structure suitable quality improvement programs.

Fungal effectors, the double edge sword of phytopathogens.

Phyto-pathogenic fungi can cause huge damage to crop production. During millions of years of coexistence, fungi have evolved diverse life-style to obtain nutrients from the host and to colonize upon them. They deploy various proteinaceous as well as non-proteinaceous secreted molecules commonly referred as effectors to sabotage host machinery during the infection process. The effectors are important virulence determinants of pathogenic fungi and play important role in successful pathogenesis, predominantly by avoiding host-surveillance system. However, besides being important for pathogenesis, the fungal effectors end-up being recognized by the resistant cultivars of the host, which mount a strong immune response to ward-off pathogens. Various recent studies involving different pathosystem have revealed the virulence/avirulence functions of fungal effectors and their involvement in governing the outcome of host-pathogen interactions. However, the effectors and their cognate resistance gene in the host remain elusive for several economically important fungal pathogens. In this review, using examples from some of the biotrophic, hemi-biotrophic and necrotrophic pathogens, we elaborate the double-edged functions of fungal effectors. We emphasize that knowledge of effector functions can be helpful in effective management of fungal diseases in crop plants.

Risk for deep fungal infections during IL-17 and IL-23 inhibitor therapy for psoriasis.

Psoriasis is an inflammatory disease with both skin and joint manifestations. Focused biologics have been developed to target specific cytokines implicated in psoriasis and are becoming increasingly utilized. Recently, the advent of newer biologics, including IL-17, IL-12/IL-23, and IL-23 inhibitors, have garnered interest as promising treatments for psoriasis and other inflammatory conditions. Although IL-17 and IL-23 have been studied in the pathophysiology of psoriasis, they also play a central role in immunologic defenses, including those against fungi. Therefore, use of these interleukin inhibitors may theoretically impair the immune system against deep fungal infections. We reviewed the available literature investigating the risk for invasive fungal infections in patients treated with IL-17 and IL-23 inhibitors for psoriasis or other inflammatory conditions. Randomized controlled trials (RCTs), including extended trials and clinical trials, were reviewed, and we found that although there was a small number of patients who developed superficial candidiasis, there were no reports of invasive fungal disease. Although these results support the safety and the low risk for deep fungal infection with these biologics, caution is still warranted, as these medications are relatively new. Appropriate screening and management of fungal disease should still be practiced when utilizing these medications in the treatment of psoriasis and other inflammatory conditions.

The challenges and opportunities of invasive fungal disease management in the era of targeted therapy

靶向治疗的应用一方面改善了肿瘤的治疗；但另一方面，由于靶向药物所针对的靶点通常也是生理状态下免疫通路或者细胞通路的关键成分，从而损害正常免疫功能，导致包括侵袭性真菌病（IFD）在内的感染性并发症风险增加。靶向治疗的广泛应用已经或正在使对IFD风险的认识及防控策略发生变化。这种变化对于血液科医师在新时代对IFD的认识与诊断提出了新的挑战。.

Efficacy of epsilon-poly-L-lysine inhibition of postharvest blue mold in apples and potential mechanisms

Penicillium expansum is a major postharvest fungal pathogen and is the causal agent of blue mold decay in apples. Epsilon-poly-l-lysine (ε-PL) is a naturally-occurring polypeptide that has strong antimicrobial activity. It is primarily used to suppress foodborne pathogens in bread, beverage, meat products, etc. The potential application of ε-PL in the management of fungal postharvest diseases of fruit, however, has not been explored. In the present study, the inhibitory effect of ε-PL against blue mold (P. expansum) disease of apples and its potential mechanism of action were investigated. Results indicated that 600 mg L−1 of ε-PL could effectively inhibit mycelial growth of P. expansum in apples. Concentrations of ε-PL > 200 mg L−1 also inhibited germination of conidia and germ tube growth of P. expansum in potato dextrose broth (PDB). The inhibitory effect increased with increasing concentrations of ε-PL concentration. Further studies indicated that the possible mechanisms involved of ε-PL inhibition of P. expansum included the activation of defense-related enzyme activity and gene expression in apple fruit tissues. This included polyphenol oxidase (PPO), catalase (CAT), peroxidase (POD) and phenylalanine ammonialyse (PAL). ε-PL stimulated the production of intracellular reactive oxygen species (ROS) and degraded the integrity of the cell wall and plasma membrane of conidia, resulting in the death of conidial spores of P. expansum or their germination.