Aspergillus Newsletter
April 2015

Running The London Marathon to Raise Awareness for Serious Fungal Infections

The Fungal Infection Trust are trying to get maximum leverage out of winning a rare place at the 2015 London Marathon. Dr Jenny Long (Trainee ENT surgeon at Northwick Park Hospital, London).
Mushroom Hat
Jenny has graciously agreed to wear this remarkable and quite beautiful hat while she attempts to complete her first marathon - custom made by Vlasta. 
 
Jenny has taken the hat out for a 'warm-up' run at her local park and you can see the eyecatching result here. Much as we appreciate the finer points of the many and varied strengths of fungi, this might well be the fastest mushroom ever recorded!
 
Our aim is to raise as much awareness for serious fungal infections as we can - it must be going to be easy to find Jenny in the running throngs on the morning of Sunday 26th April!
 
We also have a target to earn £130 000 to research into why some people get aspergillosis and others do not. We know that genetics is playing a part as we have done some of the preliminary work but much more work is needed to get better answers that will ultimately help us prevent aspergillosis, and may even provide clues to improve diagnosis. Donate via Text send ASPE14 £5 to 70070 or go to www.fit.org.uk
News
We have added a brief new section to the Aspergillus Website that covers prehistoric fungi. The earliest fungi have been detected at 1430 million years ago and seem to have dominated the landscape of earth forming huge 26 foot high 3 foot wide structures (Prototaxites) that until recently were assumed to be early woody trees. We have gathered together some of the most relevant papers for reference.
 
FUNGAL CELL WALL 2015 the Fungal Cell Wall 2015 meeting is to be held on the campus of the Institut Pasteur in Paris from 26-28 October, 2015. This meeting will gather the leaders in fungal cell wall biology, immunology, and antifungal mechanisms to exchange new ideas and forge new collaborations.
 
ASM 2016 brings together two of its most popular scientific sessions under one roof: ICAAC and the General Meeting will take place from June 16 - 20 2016, providing the largest gathering of microbiologists from all over the world.
 
 
7th Advances Against Aspergillosis will be held in Manchester, UK on 3-5th March 2016.
Articles
NOTE access to all articles now requires registration (free of charge)
 
A comprehensive diagnostic approach using galactomannan, targeted b-D-glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients
We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Baseline chest computerized tomography (CT) was performed pre-therapy. Twice-weekly surveillance with galactomannan (GM) was combined with targeted b-D-glucan (BDG) testing on patients with possible IFD or who were GM-positive. Combined GM/BDG detected all biopsy-proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort. NOTE supplementary data suggests prophylactic regimen method.

Th17 cytokine deficiency in patients with Aspergillus skull base osteomyelitis
Fungal skull base osteomyelitis (SBO) is a severe complication of otitis externa or sinonasal infection, and is mainly caused by Aspergillus species. Here we investigate innate and adaptive immune responses in patients with Aspergillus SBO to identify defects in the immune response that could explain the susceptibility to this devastating disease. We show that patients with Aspergillus skull base osteomyelitis infection have specific defects in Th17 responses. Since IL-17 and IL-22 are important for stimulating antifungal host defense, we hypothesize that strategies that have the ability to improve IL-17 and IL-22 production may be useful as adjuvant immunotherapy in patients with Aspergillus SBO.

Quantitative proteomic study of Aspergillus fumigatus secretome revealed deamidation of secretory enzymes.
The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by adopting liquid chromatography tandem mass spectrometry. The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulate expression of specific cellulases and hemicellulases, and expression level as a function of substrate. Post translational modifications revealed deamidation of key cellulases including endoglucanases, cellobiohydrolases and glucosidases; and hemicellulases and lignin degrading enzymes. The knowledge on deamidated enzymes along with specific sites of modifications could be crucial information for further functional studies of these enzymes of A. fumigatus.
Reviews/Overviews
Multiple mechanisms contribute to the development of clinically significant azole resistance in Aspergillus fumigatus
Azole drugs are effective against this pathogen but resistant isolates are being found more frequently. Infections associated with azole resistant A. fumigatus have a significantly increased mortality making understanding drug resistance in this organism a priority. The target of azole drugs is the lanosterol α-14 demethylase enzyme encoded by the cyp51A gene in A. fumigatus. Mutations in cyp51A have been described that give rise to azole resistance and been argued to be the primary, if not sole, contributor to azole resistance. Here, I discuss recent developments that indicate multiple mechanisms, including increased expression of ATP-binding cassette (ABC) transporter proteins, contribute to azole resistance. ABC transporters arewell-established determinants of drug resistance in other fungal pathogens and seem likely to play a similar role in A. fumigatus.
Filamentous fungal infections of the cornea: a global overview of epidemiology and drug sensitivity.
Fungal keratitis is a serious suppurative, usually ulcerative corneal infection which may result in blindness or reduced vision. Epidemiological studies indicate that the occurrence of fungal keratitis is higher in warm, humid regions with agricultural economy. The most frequent filamentous fungal genera among the causal agents are Fusarium, Aspergillus and Curvularia. A more successful therapy of fungal keratitis relies on precise identification of the pathogen to the species level using molecular tools. As the sequence analysis of the internal transcribed spacer (ITS) region of the ribosomal RNA gene cluster (rDNA) is not discriminative enough to reveal a species level diagnosis for several filamentous fungal species highly relevant in keratitis infections, analysis of other loci is also required for an exact diagnosis. Molecular identifications may also reveal the involvement of fungal species which were not previously reported from corneal infections. The routinely applied chemotherapy of fungal keratitis is based on the topical and systemic administration of polyenes and azole compounds. Antifungal susceptibility testing of the causal agents is of special importance due to the emergence and spread of resistance. Testing the applicability of further available antifungals and screening for new, potential compounds for the therapy of fungal keratitis are of highlighted interest.

Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?
Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the ‘gold standard’ against which newer tests are judged. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.
Deadlines
June 30th Deadline for early bird registration for ProkaGENOMICS 2015
July 31st Deadline for early bird registration ERS 2015
Courses
Masters in Medical Mycology, University of Manchester, UK 2015-2016 Applications for this one-year taught Masters programme in Medical Mycology are now open. Following its launch in 2013 this unrivaled degree has attracted scientists and clinicians from all over the globe who have acquired practical and clinical science skills which will help them succeed in becoming mycology ambassadors and practitioners in their home countries. The Faculty for the Manchester Medical Mycology programme is world-renowned with a number of leading scientists, clinician scientists and medical mycologists.
 
Molecular Mycology: Current Approaches to Fungal Pathogenesis Woods Hole, Falmouth, MA, USA. 14 - 30 June 2015
 
Global Clinical Scholars Research Training, Harvard University, USA. (Various information sessions worldwide). First workshop June 19-20th 2015.More information.
 
The Gorgas Courses in Clinical Tropical Medicine The Gorgas Diploma 26th January - 27th March 2015. To be held in Peru: Application forms online from Oct 1st  2014 (Course for 2014 fully booked). More information
 
HFP2015, the 6th FEBS Advanced Lecture Course on Human Fungal Pathogens, May 16-22, 2015. La Colle-sur-Loup, France:first announcement
Veterinary
Survey of bovine mycotic mastitis in different mammary gland statuses in two north-eastern regions of Algeria.
The aim of this study was to evaluate the prevalence of mycotic mastitis in different mammary gland statuses. The study was conducted on 304 dairy cows from ten farms in two north-eastern regions in Algeria; Guelma and Souk Ahras with 922 and 199 samples, respectively, forming thus a total number of 1,121 milk samples. A total of 321 milk samples were collected from clinical mastitis, 544 milk samples from subclinical mastitis and 256 milk samples from healthy mammary glands. Mycological analyses revealed that 10.17 % of the treated samples were positive recording 114 species of fungi including 88 yeasts and 26 moulds. The most frequent species was Candida kefyr followed by C. albicans, C. guilliermondii, C. famata, C. tropicalis, C. colliculosa, C. krusei, C. rugosa, C. glabrata, C. parapsilosis, C. inconspicua, Trichosporon sp., Rhodotorula glutinis and Saccharomyces fragilis. Mould species have also been isolated from samples of both healthy milk and clinical mastitis milk.
Attention Clinicians & Scientists
Nominate fungal (incl. non-pathogenic) genomes for sequencing at the Joint Genome Institute (JGI) here
 
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Patients
The Aspergillosis Community meeting takes place on 1st May back at our regular venue in the Altounyan Suite, North West Lung Centre at 1pm. This month we will have Consultant Chris Kosmidis answering your questions so if you have anything you would like to ask please left us know via admin@aspergillus.org.uk as soon as possible
 
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Current Fundraising events:
Wendy Fuller's runners are holding their event on May 9th 2015
 
 
Floral Teddy in Memory of Denise Barnes
Wendy Fuller's runners in memory of Ann Barnes
 
 
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