Wednesday, 29 June 2011

NewsBites: Aspergillus Oryzae Complete Sequence Published

The latest complete genome sequence of an Aspergillus species has been published in the genome databank Genbank.

Aspergillus oryzae is mainly known as a species that has been used by the food industry in the East for many hundreds of years (Soy sauce, koji, sake), but is also occasionally a human pathogen. The availability of this latest sequence is in addition to a different strain of the same species sequenced 6 years ago. Much is known about the differences in the characteristics of these 2 different strains and now we can compare the genome sequences we can start to 'map' those differences to variations in the DNA sequence of the two strains. Much will be learned during this process.

Tuesday, 28 June 2011

Ten per cent of Patients taking Triazoles for Chronic Pulmonary Aspergillosis suffer from neuropathy

The National Aspergillosis Centre treats chronic fungal infections using antifungal drugs, often as a means to reduce the dose of steroids necessary to maintain good breathing. The main drugs used are the triazoles - in order of historic availability: itraconazole, voriconazole and more recently posaconazole which have many advantages over their predecessor, amphotericin B and its derivatives.

The nature of the treatment is to provide antifungal for extended periods of time as although it is active against the fungus it cannot eradicate the fungus as a general rule, it simply keeps it in check. Any drug taken for long periods of time is likely to start to cause unwanted side effects and triazoles are no different, as a quick glance at the list of side effects will testify.

The National Aspergillosis Centre uses these antifungals to treat rare conditions such as chronic pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS), none of which have been extensively studied with regard to side effects caused by the triazole drug used to treat, partly because this is a fairly recent, novel use for these antifungals.

One particularly problematic side effect noted was a collection of symptoms consistent with peripheral neuropathy; numbness and tingling of the fingers & toes, limb weakness. This is potentially a serious side effect which can necessitate the patient stopping treatment. Consequently a study has been carried out to look at how frequent peripheral neuropathy symptoms occurred in patients taking long term triazole therapy.

Results Between 2007 and 2010 those of those patients taking itraconazole, 17% developed peripheral neuropathy, of those taking voriconazole 9% developed peripheral neuropathy and for posaconazole the figure was 3%.

It is noteworthy that the newer drugs are better in this respect - they cause less neuropathy. Unfortunately they are also the more expensive drugs so most patients will have to be tried on the cheaper drugs first. This study shows us the importance of monitoring patients on triazoles for signs of neuropathy (and patients monitoring themselves), and also shows us that there is a clear progression available to patients where they can be put onto less side effect prone triazoles if needs be.

Monday, 27 June 2011

NewsBites: What makes Aspergillus fumigatus such a good pathogen?

Aspergillus fumigatus is usually described as requiring good levels of oxygen to support growth. However when growing as a pathogen in a human body there are poor levels of available oxygen - hypoxic conditions.
A recent report in the Journal of Proteome Research,
"The mold Aspergillus fumigatus is the most important airborne fungal pathogen. Adaptation to hypoxia represents an important virulence attribute for A. fumigatus. Therefore, we aimed at obtaining a comprehensive overview about this process on the proteome level."
This led to "identiļ¬cation of 117 proteins with an altered abundance under hypoxic in comparison to normoxic conditions."

Friday, 24 June 2011

TV Soap Star Struck Down by Aspergillosis

BBC Scotland TV soap actor Frank Gallagher (not the character with the same name in the Channel 4 series Shameless) has been treated for aspergillosis. Frank played the 'hardman' Lenny Murdock in the series and was suddenly struck down with severe respiratory difficulties which did not respond to antibiotics.

Antibiotics would successfully treat the normal cause of these symptoms (bacteria) but it was only after this course of treatment failed that it was realised that Aspergillus was the culprit. One factor that makes it more difficult to diagnose Aspergillosis is that during each course of antibiotics Frank (in common with other patients suffering from this infection) felt better for a short time so making it appear that the antibiotic was working, before relapsing again. Several courses of antibiotics were probably tried before further investigations were carried out and aspergillosis was discovered as it is highly unusual for the average doctor to come across a case of aspergillosis.

In Frank's case the delay before treating his aspergillosis with an antifungal drug does not seem to have made his illness markedly worse as he now feels much better, but in some cases it can be very dangerous. Better techniques for more rapid diagnosis are desperately needed and are currently under research but there is a lot of work to do yet.

Research into diagnostic techniques is one of the main aims of the Aspergillosis research charity Fungal Research Trust and its £150 000 fundraising campaign

Frank is now well enough to return to River City thanks to a course of antifungals.

Thursday, 23 June 2011

Worlds First Double Lung Transplant for Chronic Pulmonary Aspergillosis

Becky Jones has Cystic Fibrosis (CF) which in common with many other people who live with CF  makes her lungs vulnerable to infection.  Aspergillosis is a common infection for this group of people (up to 11% of people with CF get aspergillosis), usually in the form of ABPA but this occasionally progresses to the more aggressive forms of aspergillosis such as Chronic Pulmonary Aspergillosis.
No forms of aspergillosis are currently curable with antifungal drugs and treatment usually consists of managing the condition using antifungals and steroids in order to prevent scarring of lung tissue and loss of lung function.

Unfortunately there are increasing cases where the infecting fungus is resistant to all  usable antifungal drugs, and in those cases treatment becomes very difficult. Ultimately what is really needed is to replace the diseased tissue with new - a lung transplant.

This strategy has never been tried before as there is a 'self defeating' scenario that has to be carefully managed. Someone who has an organ transplant has to take immunosuppressant drugs to prevent rejection of the donor tissue by the patients immune system. This also makes the patient vulnerable to infection and if he/she is already infected with Aspergillus that was thought to make the patient highly likely to become re-infected. Fortunately there have been some advances in the administration of antifungal drugs direct into lung tissue, and if the tissue match is good it might be possible to minimise immunosupression - the stage was set to try to treat a CPA patient in this way.

Becky had extensive Chronic Pulmonary Aspergillosis which had became resistant to all useable antifungal drugs  so her infection could no longer be managed. Like many CPA patients Becky would most likely have been treated with steroids to minimise inflammation caused by the aspergillus infection (and so allow her to breathe), which in turn would also make her a little less able to fight the infection - another 'self defeating' vicious circle but this time one that relies on the availability of an antifungal that the infection is not resistant to in order to keep the infection in check - as long as that continues the condition is manageable. In Becky's case there was no antifungal left to use, there was no alternative but to consider a transplant.

To look at Becky in the news reports is to see the hope that this technique, used for the first time to treat CPA can bring. She will now be closely monitored to check for infection and will be given an antifungal 'inhaler' to keep aspergillosis at bay. Becky is a pioneer and is leading the way for hopefully many more in the future.

Becky is also a torchbearer for the new £150 000 fundraising appeal for the UK's foremost aspergillosis research charity The Fungal Research Trust. This appeal aims to provide a new postdoctoral researcher for 3 years to work towards new diagnostic techniques and treatments.

Her personal message is:
" Without the research they have funded, my new lease of life would not be possible. As a young child I coped pretty well with my cystic fibrosis. When I was about 10 I first got Aspergillus infections - which never went away. In my teens, I was often miserable and had lots of steroid medicine. Later balls of fungus were found inside my lungs. Antifungal treatment helped a bit to start with and then stopped working, because my Aspergillus had developed resistance to the treatment. The only way to improve my life was a double lung transplant and receiving intravenous Antifungals. I have made it through the transplant and I can breathe again– please help support the campaign because I have made it through – please help others make it through their difficult times with fungal infection.” Becky's story
(visit Press release)

The Fungal Research Trust works closely with the National Aspergillosis Centre in Manchester, UK

Thursday, 16 June 2011

Aspergillus as Beautiful Art Pieces

Aspergillus flavus by Fiona Hepburn
Fiona Hepburn's work (currently being exhibited by Hemingway) is strongly anatomical. She recreates extraordinary detailed pieces featuring fungi, lichen and marine and terrestrial plants, all of which are made from cut-worked paper.
Aspergillus fumigatus by Fiona Hepburn

In Aspergillus Fumigatus Fungus I (le) as in other pieces she works in exquisite detail to create tiny components by screen printing her paper and then cutting out minute sections to mount on pins, thus creating a layered vibrant work.

Constructing the work

Quoting the artist : I have always had a tendency to make sculptural work, I find it difficult to make a print and leave it untouched. I'm always eager to pierce holes, emboss the surface or cut with a scalpel. As a printmaker I am interested in the construction and reconstruction of prints. I see the potential to 'reproduce' images - like nature’s ability to regenerate; it is the force of controlling impermanence. Printmaking is a reproduction process; it is a way of making a multiple, a way of reproducing an image over and over again.
The final images I produce are one-off pieces, made up of thousands of multiples. Each tiny 'spore' is printed using hand drawn stencils exposed on to a screen. The screenprinted spores are printed on to fragile Japanese paper. I reproduce the spores until I have thousands of them, often in variations of colours and tones. Each tiny 'spore' is hand cut with a scalpel and attached to a pin. I construct the work by pushing these pins in to a background image either made through screenprint or woodcut. It allows me to control the growth of the image, allowing for different parts of the image to be seen at different levels. Making the work is like watching the cells of growing mould multiply. The labour intensive, obsessive process is an integral part of my practice. The cutting and piercing is irreversible and destructive, and it mimics the precarious, fragile state of the natural world.

Spores by Fiona Hepburn   
Hepburn is holding a tempting ‘come and make’ session on the afternoon of July 3, where, under her tutelage, one can create one’s own screen print and cut work.

The exhibition is at HEMINGWAYART, Cassington, Oxford, UK and open Thursday to Sunday 2-7pm continuing till July 3.

Wednesday, 15 June 2011

NewsBites: Easy to Mistake Bipolaris Infection for Aspergillosis

Veterinary Pathology journal reports:
 a case of Bipolaris infection in a dog with granulomatous meningoencephalitis, nephritis, and vasculitis. The clinical and histological features resembled those of the more common aspergillosis, thus warranting confirmation by molecular methods.

Tuesday, 14 June 2011

NewsBites: Endotoxin Impairs Excretion of Antifungal Drug, Micafungin

Experiments reported in the Journal of infection and chemotherapy show that endotoxin reduces the excretion of micafungin (commonly used to treat aspergillosis and other fungal infections). The authors suggest this information could be useful when treating endotoxemia, reducing the need for dose adjustments.

Friday, 10 June 2011

NewsBites: An Attempt to Distinguish Invasive Pulmonary Aspergillosis (IPA) and Pulmonary Lymphoma (PL)

Scientists in Basel, Switzerland have attempted to find reliable criteria to distinguish invasive pulmonary aspergillosis (IPA) and pulmonary lymphoma (PL) using CT scanning techniques due to the high level of detail offered by this technique.
The attempt concluded that CT could only be suggestive for either IPA or PL, it was not possible to distinguish between these two conditions using CT alone and that other addtional tests are necessary.

Thursday, 9 June 2011

NewsBites: Patients' Mobiles Phones carry Aspergillus & Other Pathogens

A recent study in the American Journal of Infection Control (abstract) and covered in some detail by The Times of India examines the fungal and bacterial contamination found on the mobile phones of doctors and their patients. Potentially a route of infection, mobile phones of doctors were found to be contaminated in an earlier study (opening up the possibility that doctors may need to pay more attention to how and where they use their phones), but this study shows twice as many mobile phones owned by patients are contaminated compared with doctors - suggesting doctors are already cleaner mobile phone users compared with the general population.
Regardless, we all need to be aware of the potential of infection of the devices we all carry around.

Wednesday, 8 June 2011

NewsBites: Invasive Pulmonary Aspergillosis increasingly associated with Hepatitis B infection

NewsRx website reports:
"Invasive pulmonary aspergillosis (IPA) has been increasingly frequent in severe liver disease. We aim to investigate the clinical presentation, predisposing factors, and treatment of IPA in patients with liver failure caused by hepatitis B virus (HBV) infection scientists in Shijiazhuang, People's Republic of China report."
 "Medical records from 798 patients with HBV-related liver failure were reviewed. A total of 43 patients with probable IPA were selected as the case group, another 43 patients with bacterial infection and 43 patients without any infections were selected"
 "Patients with HBV-related liver failure are predisposed to IPA and may have a more severe condition and poorer prognosis."

Tuesday, 7 June 2011

NewsBites: Peking University devises Rapid Test for Fungi in Sinusitis

NewsRx website reports:
"According to recent research from Beijing, People's Republic of China, "Rapid detection and differentiation of Aspergillus and Mucorales species in fungal rhinosinusitis diagnosis are desirable, since the clinical management and prognosis associated with the two taxa are fundamentally different. We describe an assay based on a combination of broad-range PCR amplification and reverse line blot hybridization (PCR/RLB) to detect and differentiate the pathogens causing fungal rhinosinusitis, which include five Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, and A. nidulans) and seven Mucorales species (Mucor heimalis, Mucor racemosus, Mucor cercinelloidea, Rhizopus arrhizus, Rhizopus microsporus, Rhizomucor pusillus, and Absidia corymbifera).""

Monday, 6 June 2011

Aspergillus niger provides clues to help solve our future energy crisis

Motorists will be very aware that the price of petrol and diesel fuels are rising ever faster as supply fails to meet demand throughout the world. Some of this shortage is due to political troubles in oil producing parts of the world and some due to ever increasing demand in parts of the world that are formerly low consumers of energy per head of population eg China & India. See also this graph of daily oil consumption around the world.

Of course ultimately gas & oil supplies will dwindle as stocks are finite (report), so the stage is set for further price rises, to levels that make the use of traditional fuels for vehicles unaffordable and impractical. New fuels must be found, preferably cleaner fuels!

As the search for new ways to power the world's transport goes on Aspergillus is playing its part. Aspergillus is already well established as an organism that can be used to mass produce substances like citric acid, enzymes & food supplements via fermentation technology.
Aspergillus niger (Aspergillus website Wikipedia) is particularly good  at breaking down complex materials such as polysaccharides (e.g. cellulose plant stalks - often thrown away) into useful sugars, thus making food production more efficient by making use of waste by-products of the food & farming industries.

Very similar technology can be used to break down waste matter into simple molecules that can be used as cleaner-burning biofuels while at the same time not using up valuable foods such as grain - currently a major problem for the scaling up of the production of biofuels.

While Aspergillus niger is already good at this process, every little improvement counts in this vital race to secure our energy production for the future. This is where research into the genomes of Aspergillus niger comes in.  Sequencing entire A. niger genomes, each taken from strains of A. niger that are used in different parts of the fermantation industries and comparing them with each other it is hoped that we can learn more about how each strain works, why some are better at some parts of the process that others and so on in the hope of improving all strains for our own purposes.

Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88.

So successful was this approach many further strains are being sequenced to be subjected to the same analysis.

Aspergillus is a serious pathogen of humans and animals and as such quite rightly gets a bad press, but here we can see that it is also a formidable ally if used and controlled. It may even help solve the worlds forthcoming energy crisis!

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