Sex for Aspergillus fumigatus discovered
Top news is the discovery of a sexual cycle in the pathogenic fungus Aspergillus fumigatus which has just been described in Nature by Scientists from The University of Nottingham and University College Dublin. 
First described 145 years ago this killer fungus, previously had no known sexual cycle and was only thought to reproduce by the production of asexual spores. Dr Paul Dyer (from Nottingham University) is an expert in the sexual development and population variation of fungi said "This discovery is significant - providing both good and bad news. The bad news is that we now know that Aspergillus fumigatus can reproduce sexually, meaning that it is more likely to become resistant to antifungal drugs in a shorter period, and the sexual spores are better at surviving harsh environmental conditions. The good news is that we can use the newly discovered sexual cycle as a valuable tool in the laboratory."
The discovery of a sexual cycle in A. fumigatus provides insights into the biology and evolution of the species. It helps explain the presence of diverse genotypes despite predominantly clonal reproduction, the conservation of sex-related genes, aspects of genome evolution and defence against repetitive elements. In addition, production of ascospores might aid survival in adverse environmental conditions. The discovery has significant medical implications. Sexual reproduction can result in progeny with increased virulence or resistance to antifungal agents, and can confound diagnostic tests based on the assumption of clonality.
It is hoped the results of this research will lead to new ways of controlling this deadly disease and improved treatments for patients infected with it.
Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus Céline M. O'Gorman,, Hubert T. Fuller,& Paul S. Dyer. Letters to Nature (online) 30th Nov 2008.
This Month
Following on from last month which featured new classes of antifungal drugs emerging at the ICAAC/IDSA 2008 conference, we highlight a number of new topical articles relating to antifungal resistance.
The prevalence of itraconazole resistance amongst clinical A fumigatus isolates was studied in 1219 patients from a centre in the Netherlands. They conclude that azole resistance has emerged in A. fumigatus (32 isolates (2.6%)) and might be more prevalent than currently acknowledged. The presence of a dominant resistance mechanism in clinical isolates suggests that isolates with this mechanism are spreading in our environment.
In addition two recent reviews entitled "Outwitting Multidrug Resistance to Antifungals' and 'The fight against fungi' explore the mechanisms of multidrug resistance in yeast and Candida. 
There is also a comprehensive review in the Japanese Journal of Medical Mycology entitled 'Antifungal resistance mechanisms of Aspergillus'. Understanding drug resistance in fungi is forging ahead!
A series of abstracts from the recent ICAAC meeting and several reviews written this year which we have arranged into a new subsection of the library.
Latest News and Articles
AspICU is a web-based surveillance project of Aspergillus in Intensive Care Units, currently looking for Physicians and researchers to contribute. This is an international, observational survey of ICU patients with evidence of either Aspergillus colonization or invasive aspergillosis, aiming to collect a large series of ICU patients. The gathered data will be used to investigate the epidemiology of invasive aspergillosis in ICU patients, and to validate a diagnostic algorithm that discriminates colonization from invasive disease. For further details visit http://www.aspicu.org
There have been 54 additions (6 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:
Micafungin alone or in combination with other systemic antifungal therapies in hematopoietic stem cell transplant recipients with invasive aspergillosis
Evaluation of 98 hematopoietic stem cell transplant recipients of whom 83 were refractory, treated either by monotherapy or in combination therapy with micafungin supported the use of micafungin -even at high doses - for the treatment of IA in this high risk patient group.
Limitations to the study included the small sample population, amongst others- but the need for a randomised trial of echinocandins in combination with other anti-fungals in this patient group was highlighted.
Is there a need for autopsies in the management of fungal disease?
The decline in autopsy rates in many countries partly due to lack of acceptance by both society and in part the medical profession has been studied in relation to patients with infectious diseases. Data indicates that 20-30% of patients have undetected lesions which can be found at autopsy and some rare fungal diseases are diagnosed by autopsy.
It is suggested that autopsy remains an important tool in medical diagnostic and therapeutic action and is needed in the management of fungal disease for many purposes.
A simple and reproducible 96-well plate-based method for the formation of fungal biofilms and its application to antifungal susceptibility testing
Biofilms have unique properties that can have profound effects including enhanced antifungal resistance during infection of a host. Biofilms are formed on implanted materials as well as on host tissue so work with these structures have a wide range of applicability.
In this paper a simple method is described to create biofilms in vitro for the purpose of testing these structure against antifungal drugs
Reviews
Therapeutic drug monitoring for triazoles
Triazoles have revolutionized the prevention and treatment of invasive fungal infections. There is an increasing body of data demonstarting that triazoles exhibit concentration–effect and concentration–toxicity relationships. The
pharmacokinetics and pharmacodynamics of triazoles is now better understood and this has facilitated the identification of concentrations (or drug exposures) that are both effective and nontoxic. Evidence suggests that routine monitoring of drug levels should be considered for itraconazole and voriconazole to optimize patient outcome. More clinical information is needed before recommendations are made for other triazoles.
Outwitting Multidrug Resistance to Antifungals
Recent understanding of the transcriptional regulation of plasma membrane efflux pumps of modest specificity provides new avenues for the development of broad-spectrum fungicides. Together with improved diagnosis and indirect intervention via inhibition of the energy supply for drug efflux, the authors envisage multifunctional azole analogs that inhibit not only ergosterol biosynthesis and drug efflux-pump activity but also activation of the transcriptional machinery that induces drug efflux-pump expression.
Treatment
The article/review on 'Allergic Fungal Rhinosinusitis (AFRS)' by Professor Arunaloke Chakrabarti has now been updated and includes the definition, diagnosis and treatment of AFRS.
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.
Case Histories
A new case history entited 'ABPA and subacute invasive pulmonary aspergillosis intolerant to triazole anti-fungals and terbinafine' has been added to case histories.
Blog
A joint project between the Health and Environmental Alliance (Heal) and the European Federation of Allergy and Airways Diseases Patients Association (EFA) have launched a website "Know your Air for Health" whose objective is to help communicate EU air quality information and alerts to allergy, asthma and COPD patients in Europe.
The site contains much information on EU legislation on ambient air quality and specifically on emissions. Amongst many useful links "Find your EU pollen forecast" takes you to http://www.polleninfo.org/ where a europe-wide breakdown of pollen spore forecasts can be summarised or viewed for an individual country. Pollen types and mould spores are listed individually in a typical pollen forecast. A Countdown service to the start of the pollen/spore seasons and data charts of pollen counts for individual sites and regions are available for clients of Pollen UK. Much information is available on the site and historical data from ~300 pollen monitoring stations has been used to produce load maps of the likely intensity of pollen loads for a given month and area.
Patients
We run a highly active support group and Question & Answer bulletin boards for all patients and their relatives.
Books
A search form for Google Books has been added to the library. Containing over 10 000 books on Aspergillus this impressive project intends to make every book in the world searchable in time.
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
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.
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