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Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

Recent estimates suggest that>300 million people are afflicted by serious fungal infections worldwide. Currentantifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of newantifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi.
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news

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l W Abstract Echinocandins are antifungal nonribosomal hexapeptides produced by fungi. Two of the amino acids are hydroxy-l-prolines: trans-4-hydroxy-l-proline and, in most echinocandin structures, (trans-2,3)-3-hydroxy-(trans-2,4)-4-methyl-l-proline. In the case of echinocandin biosynthesis by Glarea lozoyensis, both amino acids are found in pneumocandin A0, while in pneumocandin B0 the latter residue is substituted by trans-3- hydroxy-l-proline (3-Hyp). We have recently reported that all three amino acids are generated by the 2-oxoglutarate-dependent proline hydroxylase GloF. In echinocandin B biosynthesis by As...
Source: Applied and Environmental Microbiology - Category: Microbiology Authors: Tags: Appl Environ Microbiol Source Type: research
This article is protected by copyright. All rights reserved. PMID: 29315506 [PubMed - as supplied by publisher]
Source: Clinical Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Pharmacol Ther Source Type: research
Wed, 01/03/2018 - 15:39News blog
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
This study shows that S. cerevisiae CYP51 adequately represents some but not all mutations in CYP51s of pathogenic fungi. Insight into the molecular mechanisms of resistance mutations in CYP51 will assist the development of inhibitors that will overcome antifungal resistance. PMID: 29263059 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load. The grafts were implanted successfully, but the pati...
Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantation - Category: Transplant Surgery Authors: Tags: Exp Clin Transplant Source Type: research
Tuesday, December 12, 2017 - 13:13Slide presentation
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Tuesday, December 12, 2017 - 13:10Slide presentation
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Fungal diseases are significant causes of mortality and morbidity in both the developed and the developing world. The recent increases in the incidence and severity of invasive fungal infections are directly attributable to new susceptible patient populations. Examples of these large, at-risk populations include patients with AIDS; hospitalized patients being treated for cancer and autoimmune disorders; andthose receiving organ transplants.Courses&Workshops
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Abstract Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, developing new clinical modalities as standalone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we test the in vitro and in vivo impact of hyperbaric oxygen (100% oxygen,>1 ATA) (HBO) on A. fumigatus proliferation and murine IPA outcomes....
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Case 1: A 20-years old woman with cystic fibrosis (CF), deltaF508 homozygote, predicted 35% FEV1 was treated with inhalative antibiotics due to colonisation with Pseudomonas aeruginosa (PA). An allergic bronchopulmonary aspergillosis has previously been treated, with no evidence of reactivation. After severe exacerbations and a drop of FEV1 to 17%, she stabilized with steroids and IV-antibiotics. Despite a reduction of Pseudomonas, a low FEV1 persisted. Yeast grew in repeated sputum cultures, but could not be identified by standard methods. ITS-sequencing revealed the presence of Blastobotrys raffinosifermentans. Adequate ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Cystic Fibrosis Source Type: research
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