New Antifungal Classes
 The biggest antifungal conference of the year happened late last month as the combined ICAAC/IDSA meeting took place in Washington DC, USA. One of the most remarkable features of this year's event was the number of new antifungal agents that were presented. There were 3 new classes on show that had anti-Aspergillus activity represented by:
- FG3409, which works by selective inhibition of a fungal enzyme
- T-2307, an arylamidine representing another new class of antifungal
- ITF2534/7, a histone deactetylase inhibitor
New classes of antifungals are particularly important as resistance to a drug can propogate quite rapidly through a single class. The more new classes of drug we have available the better for treatment of resistant infections.
In addition there was a poster investigating the antifungal (activity against Aspergillus not yet been tested) properties of the anti-cancer drug Tamoxifen and an extensive study on the new azole antifungal Isavuconazole.
Abstracts for these posters are available on the Conference Abstract section - go here and choose as conference 'ICAAC 48th' or enter the drug name as a keyword.
This month
A big story emerged when a paper (Buchud et.al.) was published showing that there is a link between donor TOLL receptor and susceptibility to invasive aspergillosis during neutropenia while undergoing transplant treatment for leukemia. We covered this story in more detail in our Blog but to summarise the Toll genes are surface receptors thought to be intimately linked with the ability of a person to fight off infections. A particular variant of Toll-like receptor 4 is associated with a 5 fold increase in vulnerability to infection by Aspergillus but only when the transplant donor is unrelated to the recipient.
In addition
"seropositivity for cytomegalovirus
(CMV) in donors or recipients, donor positivity for S4, or both, as compared
with negative results for CMV and S4, were associated with an increase in the 3-year
probability of invasive aspergillosis (12% vs. 1%, P = 0.02) and death that was not
related to relapse (35% vs. 22%, P = 0.02)."
Prior knowledge of the status of Toll receptor 4 and CMV in a patient is therefore very useful as those patients could be considered for (expensive) prophylactic antifungal treatment.
 Positron Emission Tomography (PET) can be used to detect Pulmonary Aspergillosis. We have full 3 dimensional images from scans of a patient who had a suspected tumour in their left lung which was removed by surgery after full PET & CT scans seemed to confirm the diagnosis. Unfortunately/fortunately examination of the lesion revealed dense growth of Aspergillus and no cancer.
The picture taken from the scan shown here on the right indicates the site and appearance of the lesion, but this can be seen much more clearly in 360 degree rotational presentation here.
Latest News and Articles
There have been 37 additions (3 reviews) to the articles section. Readers should also note that it is now possible to read the abstract of each article simply by clicking in the Abstract link appearing alongside each article. We have picked out a few of the highlights here:
Phase-dependent antifungal activity against Aspergillus fumigatus developing multicellular filamentous biofilms.
Aspergillus fumigatus was challenged using 3 antifungals (Amphotericin B, voriconazole and caspofungin) when the fungus was at each of three different stages of its growth. The results showed that the fungus was far more vulnerable to antifungal activity while it was in early stages of growth (8hrs) compared with later stages (24hrs). Amphotericin was most effective at all stages.
 Bioluminescent Aspergillus fumigatus: A new tool for drug efficiency testing and in vivo monitoring of invasive aspergillosis.
An interesting new way to directly follow infection in animal models. The light generated by the bioluminescence can be detected in live animals, allowing visualisation of the progression of the infection and the effect of treatment with antifungals..
There is an additional potential use for this technology. Bioluminescence requires oxygen so as an infection progresses it may be possible to follow hypoxia at the infection site.
Effective lead selection for improved protein production in Aspergillus niger based on integrated genomics.
Three widely used enzyme overproducing strains of A.niger were compared with their isogenic fungal host strains and any proteins found to be overexpressed were analysed using transcriptomics. This information was used to make changes to a strain of A. niger which made it an improved host that increased overexpression albeit marginally - specifically overexpressing oligosaccharyl transferase sttC and removing the ERAD protein degrading gene.
House suspects Aspergillosis
 TV medical drama 'House' features Aspergillosis as a possible diagnosis for a patient with bad cough and lung infiltrates on a chest x-ray. Infectious diseases specialist Dr House holds off treatment due to potential kidney toxicity caused by Amphotericin and saves the patients' life. Diagnosis turns out to be psittacosis!
Reviews
Developing Aspergillus as a host for heterologous expression
Aspergillus has a long history of use for all of the important substances it produces. More recently molecular biologists have been taking advantage of this natural ability by engineering Aspergillus to produce a wide range of proteins and other molecules.
This review covers history, state of the art and future directions of this research.
Galactomannan detection for invasive aspergillosis in immunocompromized patients
Cochrane review with the objective to summarise estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of Invasive Aspergillosis.
Treatment
The Treatment index page has been redesigned in order to group the available information more clearly and now offers abstracts of each page that can be read without registering or logging into the website.
There is also a new search section that allows all treatment pages to be searched and will allow all treatment articles stored in the library to be searched quite shortly.
Blog
Identification of an Aspergillus fumigatus protein which is involved in fungal growth in hypoxic conditions and in drug resistance
A recent study by Willger et al has explored a mechanism required by this mold to cause disease, hypoxia (low oxygen) adaptation. The study states that hypoxia adaptation in Aspergillus fumigatus is mediated in part by a highly conserved transcription factor, SrbA, a protein in the sterol regulatory element binding protein family.
A mutant strain, not expressing SrbA was found to be unable to grow in hypoxic conditions, it also displayed increased susceptibility to the azole class of antifungal drugs - specifically it was highly susceptible to fluconazole and voriconazole, and was unable to cause disease in two distinct murine models of IPA
Patients
We run a highly active support group and Question & Answer bulletin boards for all patients and their relatives.
Aspergillosis for CGD
We have renamed this group to clarify that we support aspergillosis cases amongst CGD patients and not CGD itself. For dedicated CGD support please go to the CGD charities website.
Technical Tips
Our discussion group (email and/or website) designed to promote discussion on technical issues for laboratory workers.
Searching the website
We now have a dedicated Google Search Appliance for this website. This means you can search the Aspergillus Website using Google and it will include nearly all documents on the website (pdf, doc, ppt, html, php etc). and will include parts of the secure sections and eventually index images - a big improvement on earlier search facilities. Try it out here or search the Aspergillus Cloud
HonCode
 Health on the Net Foundation (HonCode) are the formost accrediation service for health-oriented websites. The Aspergillus Website has been accredited since 1999 and this has once again been reaffirmed after the latest review in August 2007
RSS
Download our updates and articles automatically every time we add to those pages- no need to wait for the next newsletter. 40 000 pages accesses per month. Use RSS.
What is RSS and how do I use it? Get help here.
Thanks for reading!
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The Aspergillus Team.
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