Fungal Infection Trust
June 2016
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Highlights of this month...

Biofilms, diagnostics and treatment

Aspergillus species are prolific biofilm producers and so biofilms are of much interest to clinicians and researchers when faced with optimising treatment of Aspergillus infections as it has been established that once a growing isolate has formed a biofilm it becomes more difficult to treat with antifungal drugs, resistant to immune system effectors and also potentially more difficult to detect with diagnostic tests.
 
This review discusses how diagnostics services can quickly test isolates of Aspergillus for biofilm-forming activity, quantifying them as low, moderate or high biofilm producers. Biofilm activity correlate with the susceptibility of each isolate to antifungal drug treatment in vitro and may also correlate in vivo so this information may be of fundamental importance both to the clinician treating deep internal infection sites and those treating biofilms on invasive medical devices such as catheters.
 
Diagnostics can test antifungal susceptibility of isolates by allowing them to form biofilm prior to treating with antifungal drugs, and this technique is also useful to test novel drugs intended to disrupt biofilms and thus increase the effectiveness of antifungal therapy.
 
Biofilms may well be useful targets for the development of new approaches to the treatment of fungal infections. As researchers start to discover genes and gene products that are modulated in biofilm-forming fungi (and thus correlate with increased resistance to antifungal drugs) they may well discover new clues in the battle against drug resistance.
News
The Mycelium Comedian Visits the National Aspergillosis Centre and attempts to make mycology more accessible to the public!
 
Damp homes Symptoms reported by people who live in damp, mouldy homes have a long been puzzled over by the medical community as attempts to study the phenomenum have often been frustrated by variable, inconsistent results. Recently updated reviews have formally accepted that damp homes can cause asthma in children but the mechanism involved remains unsolved.

Doctors tend to treat allergies in these patients, however this month NIH researchers have reported some progress on this subject using a mouse model for inhalation of fungal spores. They find that both allergic and inflammatory responses can be triggered by inhaling spores and suggest that doctors treating patients reporting illness caused by damp homes should be mindful to treat both aspects rather than allergy alone.
 
Check out CPA patient Stewart Armstrong's daily vblog An eye-opening account of what living life with aspergillosis is like, every day!
Featured Website Section
This new section lists many of the new candidate drugs in development that have some activity against Aspergillus. For brevity we have tried to limit the list to those that have at least successfully passed through a phase one clinical trial. Likewise when a new drug is finally approved for use against aspergillus we will remove it from the list, moving it to the treatment section of the website.
 
The information we are storing about each drug & trial comes from a variety of resources including clinicaltrials.gov, business news and conference abstracts, as well as any articles if available.
 
 
Search engine: Every item of information on the website is indexed by our dedicated search engine. You can refine search results by title, date, author, section (i.e. content type) so you should always be able to find what you need. 
Articles
Owning a pet was associated with ABPA in patients with CF. Future prospective multicenter longitudinal studies are needed to investigate chronological causality between pet ownership, ABPA development, and pulmonary exacerbations and to determine whether these estimates are generalizable for ABPA susceptible patients beyond CF (asthma, bronchiectasis).
 
Detection of Aspergillus fumigatus in Blood Samples from Critically Ill Patients in Intensive Care Units by Use of the SeptiFast Assay.
We retrospectively analyzed the performance and relevance of the SeptiFast assay in detecting Aspergillus fumigatus DNA in whole blood samples from 38 critically ill intensive care unit (ICU) patients with probable or proven invasive aspergillosis (IA) and 100 ICU patients without IA. The assay exhibited 66% sensitivity, 98% specificity, a 93% positive predictive value, and an 88% negative predictive value. A. fumigatus DNAemia was associated with poor outcome.
Reviews
Development of enzyme technology for Aspergillus oryzae, A. sojae, and A. luchuensis, the national microorganisms of Japan
This paper describes the modern enzymology in Japanese bioindustries. The invention of Takadiastase by Jokiti Takamine in 1894 revolutionized the world of industrial enzyme production by fermentation. In 1949, a new γ-amylase from A. luchuensis, was found by Kitahara. RNase T1 was discovered by Sato and Egami. Ando discovered Aspergillus nuclease S1. Aspergillopepsin I from A. tubingensis activates trypsinogen to trypsin. Shintani et al. demonstrated Asp76 of aspergillopepsin I as the binding site for the basic substrate, trypsinogen. The new oligosaccharide moieties Man10GlcNAc2 and Man11GlcNAc2 were identified with α-1,2-mannosidase from A. tubingensis. A yeast mutant compatible of producing Man5GlcNAc2 human compatible sugar chains on glycoproteins was constructed. The acid activation of protyrosinase from A. oryzae at pH 3.0 was resolved. The hyper-protein production system of glucoamylase was established in a submerged culture.
 
Cell wall structure and biogenesis in Aspergillus species
Aspergillus species are among the most important filamentous fungi from the viewpoints of industry, pathogenesis, and mycotoxin production. Fungal cells are exposed to a variety of environmental stimuli, including changes in osmolality, temperature, and pH, which create stresses that primarily act on fungal cell walls. In addition, fungal cell walls are the first interactions with host cells in either human or plants. Thus, understanding cell wall structure and the mechanism of their biogenesis is important for the industrial, medical, and agricultural fields. Here, we provide a systematic review of fungal cell wall structure and recent findings regarding the cell wall integrity signaling pathways in Aspergilli. This accumulated knowledge will be useful for understanding and improving the use of industrial Aspergilli fermentation processes as well as treatments for some fungal infections.
 
Aspergillus spp. is frequently isolated in respiratory samples from patients with severe COPD; however, the clinical significance of this mould is unclear and its presence may indicate temporary passage, benign chronic carriage, or onset of invasive disease. The definitive diagnosis of pulmonary aspergillosis in COPD patients is often difficult owing to the lack of specific clinical and radiological signs. However, retrospective studies show the risk for developing pulmonary aspergillosis in older patients with severe COPD, and a high number of comorbidities who have received treatment with corticosteroids and/or broad spectrum antibioties. The development of algorithms based on microbiological and radiological data and risk factors for pulmonary aspergillosis can help to differentiate between colonization and infection.
 
The purpose of this chapter is to provide an overview of the medically important fungal pathogens, as well as to discuss the patient characteristics, antifungal-therapy considerations, and laboratory tests used in current clinical practice for the immunocompromised host.
Veterinary
A total of 1011 animals (292 dogs, 229 cats, 168 horses, 100 camels, 98 cows, 60 squirrels, 37 birds, 15 sheep, 6 goats, 5 rabbits and 1 fox) suspected of having dermatomycoses were examined.
Microsporum canis (M. canis) was the most frequent fungus isolated from dogs and fox, Malassezia pachydermatis (M. pachydermatis) from cats, horses and squirrels, Trichophyton verrucosum (T. verrucosum) from cows and camels, T. mentagrophytes var. mentagrophytes from sheep, goats and rabbits, and Aspergillus fumigatus (A. fumigatus) from birds.
 
The results suggested that periodic screening of animals suspected of having dermatomycoses and necessary treatments could help in the management of their public health problem.
Courses
We have modified our listing of courses so that you can now see them as a list as well as on a calendar.
 
Medical Mycology taught MSc, University of Manchester. One year course beginning in September every year.
 
MSc/Diploma Medical Mycology (Distance Learning), University College London. Online course.
 
 
Azole Resistance in Aspergillus Fumigatus - from Fungicide to Bedside Radboud University, The Netherlands August 8-12 2016
 
Medical Biofilm Techniques 2016, Lyngby, Denmark August 22-25 2016
 
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Patients & carers
Check out CPA patient Stewart Armstrong's daily vblogAn eye-opening account of what living life with aspergillosis is like, every day (NB there is some bad language in the first video, but that is what this illness does to the calmest of people at times!)
 
Patient & Carers meeting in June welcomed Prof David Denning to talk about our use of new antifungal drugs.
 
Our meeting in July will feature talks from our surgery team on when surgery would be considered for the treatment of aspergillosis.
 
Aspergillosis Community (National Aspergillosis Centre) normally meets on the first friday of each month at the Altounyan Suite, North West Lung Centre, Manchester at 1.30pm BST/GMT. If you can't make it in person, you are welcome to listen in to our live broadcast.

If you want a text reminder when each meeting is approaching (UK only) then send us an email at admin@aspergillus.org.uk.
 
Fungal Infection Trust, PO Box 482, Macclesfield, Cheshire SK10 9AR