Multiple Fungal Infections Research Articles

Comparative transcriptome profiling and weighted gene co-expression network analysis to identify core genes in maize (Zea mays L.) silks infected by multiple fungi

Maize (Zea mays L.) is the third most popular Poaceae crop after wheat and rice and used in feed and pharmaceutical sectors. The maize silk contains bioactive components explored by traditional Chinese herbal medicine for various pharmacological activities. However, Fusarium graminearum, Fusarium verticillioides, Trichoderma atroviride, and Ustilago maydis can infect the maize, produce mycotoxins, hamper the quantity and quality of silk production, and further harm the primary consumer's health. However, the defense mechanism is not fully understood in multiple fungal infections in the silk of Z. mays. In this study, we applied bioinformatics approaches to use the publicly available transcriptome data of Z. mays silk affected by multiple fungal flora to identify core genes involved in combatting disease response. Differentially expressed genes (DEGs) were identified among intra- and inter-transcriptome data sets of control versus infected Z. mays silks. Upon further comparison between up- and downregulated genes within the control of datasets, 4,519 upregulated and 5,125 downregulated genes were found. The DEGs have been compared with genes in the modules of weighted gene co-expression network analysis to relevant specific traits towards identifying core genes. The expression pattern of transcription factors, carbohydrate-active enzymes (CAZyme), and resistance genes was analyzed. The present investigation is supportive of our findings that the gene ontology, immunity stimulus, and resistance genes are upregulated, but physical and metabolic processes such as cell wall organizations and pectin synthesis were downregulated respectively. Our results are indicative that terpene synthase TPS6 and TPS11 are involved in the defense mechanism against fungal infections in maize silk.

Augmenting the Precise Targeting of Antimicrobial Peptides (AMPs) and AMP‐Based Drug Delivery via Affinity‐Filtering Strategy

AbstractAntimicrobial peptides (AMPs) have aroused extensive attention due to their low incidences of resistance, yet their clinical transformation is thwarted by inferior selectivity and metabolic stability concerns, manifesting as rapid degradation, off‐target, and non‐selective toxicity. Here, a captivating affinity‐filtering strategy is proposed as a feasible solution for such challenges. Specifically, based on the selective affinity of AMPs toward distinct phospholipids, the membrane of host cells (e.g., erythrocytes) is pre‐bound to AMPs as the “filter,” which could screen out off‐target substances with non‐specific affinity while maintaining effective interaction with high‐affinity pathogens through competitive binding, realizing precise targeting, and enhanced stability. The practicability of the affinity‐filtering strategy has been demonstrated both in vitro and in vivo, through systematic studies on various AMPs and AMPs‐modified delivery systems with multiple fungal infection models (Candida albicans and Cryptococcus neoformans), which pose severe threats to human health worldwide yet are often neglected. AMP‐modified nanoparticles with affinity filtering exhibit reduced off‐target toxicity, sufficient binding with target pathogen, as well as a substantially elevated 21‐day survival rate from 30% (conventional drug‐loaded nanoparticles) to 70%. In summary, this strategy may provide inspiration for overcoming off‐target effects in drug targeting and further promote the clinical application of AMPs.

Can Biological Control Agents Reduce Multiple Fungal Infections Causing Decline of Milkwort in Ornamental Nursery?

This research evaluates biological control agents (BCAs) and fungicide alone and in combination for the management of decline caused by multiple fungi on milkwort (Polygala myrtifolia). Four experiments were performed in a greenhouse within a nursery located in Catania province (southern Italy). The activity of fungicides and biological control agents was evaluated by calculating the plant mortality (%) and recovery frequency (%) of different fungi associated with symptomatic tissue. Comprehensively, boscalid + pyraclostrobin and fosetyl-Al showed the best results in managing disease complex on milkwort. Biological control agents provided, on average, the lowest performances; nevertheless, in most cases, they were able to significantly reduce multiple infections and sometimes when combined with fungicide enhanced the effectiveness. The molecular analysis of 86 isolates obtained from symptomatic tissue allowed to identify the fungi involved in the disease as Calonectria pauciramosa, C. pseudomexicana, Fusarium oxysporum, Neocosmospora solani (syn. F. solani) and binucleate Rhizoctonia AG-R. Calonectria pseudomexicana never reported on milkwort and in Europe was inoculated on P. myrtifolia potted healthy cuttings and produced crown and root rot after 40 days. Our findings represent the first worldwide report about disease complex of milkwort caused by several fungi (Calonectria spp., Fusarium spp. and binucleate Rhizoctonia) and on the effects of integrated control strategies to manage this disease in the nursery.

Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model.

Ibrexafungerp (IBX), formerly SCY-078, is a novel, oral and intravenous, semisynthetic triterpenoid glucan synthase inhibitor in clinical development for treating multiple fungal infections, including invasive candidiasis. Intra-abdominal candidiasis (IAC) is one of the most common types of invasive candidiasis associated with high mortality largely due to poor drug exposure in infected lesions. To better understand the potential of IBX to treat such infections, we investigated its penetration at the site of infection. Using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed high-pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we investigated tissue distribution and lesion-specific drug exposure of IBX in a clinically relevant IAC mouse model. After a single-dose treatment, IBX quickly distributed into tissues and efficiently accumulated within lesions. Drug concentrations of IBX within the liver abscesses were almost 100-fold higher than the serum concentration. In addition, drug penetration after repeated treatment of IBX was compared with micafungin. IBX exhibited robust and long-lasting lesion penetration after repeated treatment. These data indicate that IBX penetrates into intra-abdominal abscesses highly efficiently and holds promise as a potential therapeutic option for IAC patients.

Mesenteric panniculitis and rhabdomyolysis complicated by invasive fungal co-infection in a case of systemic lupus erythematosus: An autopsy report

Invasive fungal infections are a significant cause of morbidity and mortality in patients systemic lupus erythematosus. The case illustrates the autopsy findings in a patient with systemic lupus erythematosus complicated by multiple fungal infections. Rare, uncommon manifestations of SLE such as mesenteric panniculitis and rhabdomyolysis were also present. High index of suspicion with timely intervention with aggressive antifungal was life-saving.

Evaluation of the toxicity of fungicides to flight muscle mitochondria of bumblebee (Bombus terrestris L.)

Insects pollinate 75% of crops used for human consumption. Over the last decade, a substantial reduction in the abundance of pollinating insects has been recorded and recognized as a severe matter for food supply security. Many of the important food crops destined for human consumption are grown in greenhouses. A unique feature of greenhouse agriculture is the extensive use of fungicides to curb multiple fungal infections. The most widely used pollinating insects in greenhouses are commercially reared bumblebees. However, there is no data regarding the toxicity of fungicides to bumblebee mitochondria. To fill this gap in knowledge, we examined the effects of 16 widely used fungicides on the energetics of the flight muscles mitochondria of Bombus terrestris. We found that diniconazole and fludioxonil uncoupled the respiration of mitochondria; dithianon and difenoconazole inhibited it. By analyzing the action of these inhibitors on mitochondrial respiration and generation of reactive oxygen species, we concluded that difenoconazole inhibited electron transport at the level of Complex I and glycerol-3-phosphate dehydrogenase. Dithianon strongly inhibited succinate dehydrogenase and glycerol-3-phosphate dehydrogenase. It also strongly inhibited mitochondrial oxidation of NAD-linked substrates or glycerol 3-phosphate, but it had no effect on the enzymatic activity of Complex I. It may be suggested that dithianon inhibits electron transport downstream of Complex I, likely at multiply sites.

Onychomycosis due to Aspergillus niger with concomitant multiple fungal infections in a human immunodeficiency virus infected person

Opportunistic fungal infections are common in human immunodeficiency virus (HIV) infected patients and commonly occur at some point during their illness. Though estimates show that these infections can occur in HIV patients with the same frequency as in the control group, their presentations are more severe and variable in HIV/acquired immunodeficiency syndrome. We present an HIV infected case with multiple fungal infections. This patient had onychomycosis due to Aspergillus niger, tinea cruris caused by Trichophyton rubrum, oral thrush and balanoposthitis due to Candida albicans.

Multiple fungal infection in a patient on chronic low dose corticotherapy.

Multiple fungal infection in a patient on chronic low dose corticotherapy.

Clinical Experience in Invasive Fungal Infections: Multiple Fungal Infection as the First Presentation of HIV

Fungal infections constitute an important cause of morbidity and mortality in HIV-infected patients. The authors describe the case of a 40-year-old healthy male patient with a 2-month history of fever, shivers, asthenia and anorexia, who had lost weight during the past 6 months. Laboratory investigations revealed a positive HIV screening. Computed tomography scans of the chest and abdomen showed thoracic and lumbo-aortic adenopathies. Cryptococcus neoformans was isolated from cultures of blood, bone marrow, cerebrospinal fluid and from material obtained by transbronchial biopsy. Moreover, Cryptococcus spp. were seen in the lymph node biopsy. Pneumocystis jirovecii was isolated from bronchoalveolar lavage, whereas Aspergillus fumigatus and Aspergillus flavus were detected in material from a transbronchial biopsy. The patient initially received treatment with sulfamethoxazole plus trimethoprim and amphotericin B, which resulted in a substantial clinical improvement. After the diagnosis of invasive aspergillosis, amphotericin B was replaced by voriconazole as antifungal therapy and antiretroviral therapy was added. The simultaneous occurrence of three different infectious diseases-disseminated cryptococcosis, invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonitis-in a HIV-infected patient is extremely rare and there is no doubt that both early diagnosis and treatment are crucial for the patient's chances of survival.

Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento

Fungal keratitis is a characteristic infection upon tropical zones, associated with vegetal trauma. Doubt exists about the best diagnostic test and the effectiveness of available treatment. Which is the best diagnostic method for fungal keratitis? And, which is the best management? Fungal culture remains as diagnostic gold standard of fungal elements. As of treatment, natamycin and amphotericin B are the most popular drugs for fungal keratitis and they have not shown effectiveness in randomized controlled trials or systematic reviews. Voriconazole showed effectiveness and security in multiple fungal infections. It may be the drug of choice in optimal conditions, because of its better ocular penetration and wider coverage. However, its high price difficult general application. This review establishes management recommendations and the need to perform studies that address cost-effectiveness analysis of voriconazole for fungal keratitis.

Absidia corymbifera in a Patient With Chronic Granulomatous Disease

To the Editors: In the review article on zygomycosis in children by Zaoutis et al1 it is clearly outlined that this rare but life-threatening infection does occur in individuals with predisposing factors, such as neutropenia in hematopoietic stem cell transplant recipients and patients with hematological malignancies, diabetes mellitus, burns, surgery and trauma, desferoxamine therapy, as well as certain “pediatric-specific” conditions such as high-risk premature newborns, juvenile-onset (type 1) diabetes mellitus with uncontrolled diabetic ketoacidosis, and congenital metabolic aciduria. We have recently been surprised by finding widespread Absidia corymbifera infection on postmortem of a 14-year-old boy who presented 1 month before he died with signs and symptoms of acute community-acquired pneumonia. With worsening respiratory function despite broad-spectrum antibiotics, and with no diagnosis established of the underlying disease despite extensive investigations before developing adult respiratory distress syndrome requiring mechanical ventilation and treatment with high-dose steroids, he was referred for emergency support with extracorporeal mechanical oxygenation (ECMO). Open lung biopsy at that stage revealed Aspergillus fumigatus invasive pneumonia and the dihydrorhodamine neutrophil oxidative burst flowcytometry assay was diagnostic for chronic granulomatous disease (CGD), subsequently confirmed to be a result of p47phox mutation. The past medical history was uneventful except that he helped cleaning gutters of dead leaves the week before he presented. Despite combined antifungal (voriconazole and caspofungin) therapy, γ-interferon, and granulocyte transfusions, he died of multiorgan system failure. This case was reported recently as patient 1 of the series of 9 patients describing the newly recognized emergency presentation of CGD, the “fulminant mulch pneumonitis.”2 Other patients in that series, all exposed to recent inhalation of mulch, had multiple fungal infections besides Aspergillus spp., mainly with Rhizopus spp., another of the Zygomycetes class, and Penicillium spp. However, we could not find any previous reports of A. corymbifera infection in CGD, neither is that mentioned in the recent extensive review on fungal infections in primary immunodeficiency.3 Mario Abinun, MD Department of Paediatric Immunology Chris Wright, FRCPath Department of Histopathology Kate Gould, FRCPath Department of Microbiology Terence J. Flood, MA, MRCPI Department of Paediatric Immunology Jane Cassidy, MRCP Department of Paediatric Intensive Care Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne United Kingdom

Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients.

Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, AMPHOCIL), a lipid complex of amphotericin B, was developed to reduce the nephrotoxicity of amphotericin B while retaining its antifungal efficacy. In this retrospective review, the efficacy and safety of ABCD were evaluated in 220 BMT recipients (167 allogeneic; 53 autologous) with suspected or documented life-threatening fungal infections (primarily Candida or Aspergillus species). Patients were treated in five open-label clinical trials of ABCD therapy. ABCD was administered intravenously once daily, median dose of 4 mg/kg, for up to 409 days (mean 23 days, median 16 days). Successful therapeutic response to treatment (complete or partial) was reported in 52% of the 99 evaluable patients with proven infection, and in 40% of all 220 patients. In the evaluable population, the response and mortality rates were 51% and 73%, respectively, in the allogeneic BMT patients, compared to 52% and 48% in the autologous BMT patients. The response rate for evaluable patients with Candida spp was 65%, 38% for patients with Aspergillus spp, and 42 % for patients with other or multiple fungal infections. In this patient population at high risk of nephrotoxicity due to concomitant cyclosporine and/or other nephrotoxic agents, ABCD did not cause renal dysfunction. Although the majority of patients had pre-existing renal impairment (median baseline serum creatinine 1.8 mg/dl), there was no trend towards increasing serum creatinine. No unexpected toxicities were observed. In conclusion, ABCD appears to be safe and effective for the treatment of severe fungal infections in BMT patients.

Fungal Infections Of The Nose And Paranasal Sinuses: Part I

This article, the second of two, examines the following infections in detail: phaeohyphomycosis, bipolaris infections, Exserohilim infections, multiple-fungal infections, allergic dematiaceous sinusitis, Pseudallescheria infections, sporothricosis, basidoiomycetous infections, Paecilomyces infections, penicilliosis, Cryptococcus infections, and others.