Aspergillus Newsletter
February 2014

Significant Breakthrough in Stem Cell Research

Stem cells have the potential to grow into any cell type and therefore any tissue in our bodies, so consequently since they were first postulated by Maximow (b. 1874) they have been actively sought as a potential means to replace tissue and even whole organs. The snag was that stems cells are rare and difficult to find.
 
Obokata et.al. (2014) have published work this month that makes pluripotent stem cells far more readily available than they have been in the past, opening the way for more research on applications of stem cells in medicine.
 
The technique requiires no genetic manipulation and is very cheap to carry out, requiring only a blood sample and standard cell culture facilities. Previous successes at using adult stem cells generated by artificially activating particular genes have not led to widespread medical applications as in some cases it has been difficult to prevent tumour formation. This technique simply involves incubating adult mature cells in an acidic medium for 30 mins so will accelerate research and possibly even provide part of the answer to preventing tumours itself.
 
The potential for stem cell applications to treat patients with aspergillosis is very large, but it is important to state that we are some way away from rebuilding damaged lung tissue just yet, but this report takes us a significant step closer to that possibility. 
News
Fungal Genetics Stock Centre funding declined by the NSF. Alternate funding resources are need to continue operations - are you sure you paid you last invoice? Over $150 000 owed to FGSC.
 
Recent and ongoing changes to the Aspergillus Website have markedly improved our presentation of articles and we are already seeing a large increase in people registering with us so that they can download articles. Keep an eye out for the RSS icon  at the bottom of the articles pages. This means you can be automatically informed of any new articles we put up. More changes are on the way - watch this space!
 
TerrNet, A Global Aspergillus Terreus Surveillance Study is being launched by ISHAM. The aim of TerrNet is to determine the global prevalence of A. terreus in mould infections, and to broaden the knowledge on epidemiology, on clinical courses of infections and to 
investigate mechanism behind differences in amphotericin B and azole susceptibility. The group are actively seeking others who would be interested in participating, based in any part of the world. Contact Prof Cornelia Lass-Florl cornelia.lass-floerl@i-med.ac.at
 
GAFFI have highlighted two issues over the last month.
 
One is global in scope and referrs to the rate of antifungal resistance now being detected in some countries of the world. In China the numbers of resistant fungi have risen suddenly.
 
The second article highlights underfunding of UK Mycology research and states "The study concluded that despite the substantial burden of fungal disease globally, there was very little translation of preclinical research into clinical trials, nor implementation research. Few UK institutions carry out any significant amount of mycology research at all."
 
Articles
NOTE access to all articles now requires registration
 
Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated with HSCT.
 
Sensitisation to A. fumigatus was present in 13% of COPD subjects and was associated with worse lung function (forced expiratory volume in 1 s 39% predicted versus 51% predicted; p50.01), but not related to filamentous fungal culture. A. fumigatus sensitisation is related to poor lung function. Positive filamentous fungal culture is a common feature of COPD. The clinical significance of this remains uncertain.
 
Identification of genes whose mutations lead to targeted resistance can provide new information on those pathways. We used Aspergillus nidulans as a model system to exploit its tractable sexual cycle, and Calcofluor White as a model anti-fungal agent to cross-reference our results with other studies. Within two weeks from inoculation on sub-lethal doses of Calcofluor White, we isolated 24 A. nidulans adaptive strains from sectoring colonies. Meiotic analysis showed that these strains had single-gene mutations.
 
In each case the resistance was specific to Calcofluor White, since there was no cross-resistance to Caspofungin (echinocandin). Mutation sites were identified in two mutants by next generation sequencing. These were confirmed by re-engineering the mutation in a wild type strain using a gene replacement strategy. One of these mutated genes was related to cell wall synthesis and one to drug metabolism.
 
Our strategy has wide application for many fungal species, for anti-fungal compounds used in agriculture as well as health, and potentially during protracted drug therapy once drug resistance arises. We suggest our strategy will be useful for keeping ahead in the drug-resistance arms race.
 
Case reports describing skin cancer associated with voriconazole exposure emerged shortly after FDA approval, and it is now established that voriconazole is an independent risk factor for the development of cutaneous malignancy in lung transplant recipients.
The mechanism of voriconazole induced skin cancer is still unknown and may involve its primary metabolite, voriconazole N-oxide. This paper will discuss the current data and potential mechanisms of voriconazole associated photosensitivity and carcinogenesis, and identify areas requiring further research.
 
The biology, pathogenesis, molecular biology, and virulence factors of A. fumigatus have been exhaustively reviewed. This brief article focuses on how A. fumigatus is equipped with the features necessary for a ubiquitous pathogen.
Reviews/Overviews
Recent studies have suggested that biofilm formation by may be one of the most important virulence factors in IPA and aspergilloma. Several fungal constituents may contribute to the formation of biofilm structures on host cells, including cell wall components, secondary metabolites and drug transporters. The biofilm phenotype of the fungus is refractory to most conventional antifungal treatment options. Thus, an in-depth analysis and understanding of A. fumigatus biofilms is necessary to devise newer and better antifungal targets for treating complex A. fumigatus biofilm-associated diseases.
 
This review provides an overview of the different classes of antimycotics and novel antifungal compounds that induce ROS in fungal planktonic and biofilm cells. Moreover, different strategies to further enhance the antibiofilm activity of such ROS-inducing antimycotics will be discussed.
Damp & Health
Indoor Environment Professionals
Join our LinkedIn group on Damp Building and Human Health.
 
Living in a damp home?
Please check out our LinkedIn group: Is my damp home making me ill? and read our new website pages
Conference Deadlines
UKIEG 2014 - Low Carbon Buildings: What About Health and Wellbeing? (June 18th). The deadline for submission of abstracts is Wednesday 14 March 2014
 
XII Spanish National Congress on Mycology / XII Congreso Nacional de Micología(June 18th - 20th). Abstracts should be submitted by April 28, 2014.
 
Indoor Air 2014 (July 07 - 12). Early bird registration 15 March 2014
Courses
The next CBS Course in Medical Mycology will take place in Utrecht, The Netherlands, 17-28 November, 2014. 
 
Bringing PK and PD in Fungal Infections into the Clinic July 4-6 2014, Nijmegen, The Netherlands. For more information check website in January 2014.
 
Online course, Start approximately July 2014
Mechanisms in Fungal Infections is a blended, e-learning resource with CME content developed by an expert, multidisciplinary group of specialists.

How to Design and Perform your Clinical Studies in Infectious Diseases and Clinical Microbiology November 7-8, Tübingen, Germany
 
Allergy Academy, King's College, London. Online resources for allergy education. Intended for all audiences including doctors & patients.
Veterinary
A report of the course organized by the ISHAM Working Group Veterinary Mycology has appeared in Russian language, see here.
 
See thesis Natural sources against veterinary pathogens: evaluation of the anti-adhesive and anti-biofilm activity of wheat bran by González Ortiz, Gemma, Universitat Autònoma de Barcelona 2013
 
Intrastromal injection of 5% voriconazole solution may provide a safe and effective treatment option for corneal stromal abscessation in horses. In all reported cases, administration of injection early in the treatment period appeared to contribute to rapid resolution of clinical disease without significant complications. The authors present this technique as an alternative to traditional surgical intervention, being more economical, having shorter treatment duration, and potentially resulting in less scar formation.
Attention Clinicians & Scientists
An international clinical guideline on the diagnosis and management of fungal asthma is being developed. It is expected that ISHAM will be one society contributing to this effort. The WG Allergic Bronchopulmonary Aspergillosis in Asthmatics is seeking members with considerable depth of knowledge and clinical experience in this topic to contribute from outside N. America, Europe and India. Please let one of the co-ordinators know if you are interested in contributing. Contact David DenningRitesh Agarwal or Arunaloke Chakrabarti
 
Case Histories Database 230 aspergillosis cases already recorded and you can add yours too.
 
Information on mycetoma on the WHO List of Neglected Tropical Diseases can be found here, and see also the media briefing of the Mycetoma Consortium here.
 
 
The Joint Genome Institute (JGI) welcomes nominations of genomes to be sequences in its Community Sequencing Program. For procedures how to submit a proposal, see here. The current fungal program can be found here.
 
You may like to contribute to the following collaborative groups who are collecting clinical data on these rare infections:
 
Fungiscope is a global rare fungal infection registry, a working group of ISHAM.
 
International Pediatric Fungal Network (PFN) collating information on treatment of pediatric patients
 
AspICU2 is a web-based multicentre observational survey to assess the burden of aspergillosis and other fungi in critically ill patients.
Patients
 
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Also of interest...
Jobs:
 
International Research Scholars at University of Aberdeen
 
Clinical Research Fellow at the National Aspergillosis Centre, Manchester, UK
 
Clinical Microbiologist at Changi General Hospital, Singapore
 
Molecular Pathologist at Changi General Hospital, Singapore
Antifungal drug interactions
 
Antifungal drugs can interact strongly with other medications. Check your medications using our APP
 
 
Look out for our App in iTunes and Android (search for 'antifungal interactions).
 
Interactions with 739 prescription drugs are searchable, 2216 interactions listed, 443 severe.
Conferences:
 
Courses:
 
Books:

Extracellular synthesis of silver nanoparticles by Aspergillus niger by L.R.Jaidev Chakka and Narasimha Golla (11 Jan 2014)
 
Mycotoxins in Foodstuffs by Weidenbörner, Martin (25 Jul 2014)
 
Geomicrobiology and Biogeochemistry (Soil Biology)
by Parmar, Nagina and Singh, Ajay (9 Dec 2013)
 
 
The Top 100 Drug Interactions: A Guide to Patient Management by Philip D. Hansten and John R. Horn (20 Jan 2014)
Theses:
 
The Pharmacodynamics of Antifungal Agents Against Aspergillus by Jeans, Adam Rupert, University of Manchester, 2013
 
Clinical Trials (34 Recruiting):
 
 
Click map to browse
Case reports:
There are 230 aspergillosis cases reported here
 
 
 
Research Grants:
 
Lab protocols:
 
Networking:
 
News blog:
 
 
 
 
 
 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR, UK,www.fungalinfectiontrust.org.uk