Monday, 29 August 2011

NewsBite: Molecular mechanism of Aspergillus fumigatus adherence to host constituents

Inhaled conidia of Aspergillus fumigatus rapidly adhere to pulmonary epithelial cells and other host constituents. Identifying molecular mechanisms underlying A. fumigatus adherence has therefore been the focus of a number of studies aimed at identifying novel therapeutic targets.
Recent advances have suggested an important role for fungal carbohydrate components of the cell wall and extracellular matrix in adherence, including sialic acid and mannose residues, and the
newly described polysaccharide galactosaminogalactan. Read more

Wednesday, 24 August 2011

Assessment of exposure to harmful mycotoxins through breast milk in Egyptian babies

Aspergillus species cause health problems in humans and animals by direct colonisation through the lungs, but can also cause harm through the production of substances called mycotoxins. These can contaminate crops and grain when food is not dried and stored correctly.

If contaminated grain is eaten over longer periods of time -then the aspergillus mycotoxins can cause cancers, they are highly toxic also causing DNA mutations.

A recent study of 150 mothers and infants fed exclusively on breast milk in Egypt has produced some alarming results. Mothers are exposed to many toxins that can reach infants through breast milk. Scientists measured aflatoxin M1 which is excreted in breast milk and derives from several well known types of Aspergillus - such as flavus and parasiticus, found as crop contaminants.

Infant weights were documented at birth and 6 months. At 6 months - prior to weaning - aflatoxin M1 was measured along with liver markers alanine and aspartate aminotransferases, in both mothers and infants.

65% of mothers had aflatoxin M1 (>0.05ug/ml) in their breast milk - the range was 0.2- 19ug/ml. The infants of aflatoxin positive mothers had lower standard deviation scores both at birth and at 6 months. Also the levels of liver enzymes in both mothers and infants whose breast milk contained aflatoxin were significantly higher than those who were aflatoxin negative.

The study concludes that aflatoxins represent a real health threat in Egypt and the raised levels of liver enzymes in this group must be taken seriously as a potential warning for monitoring for liver cancers. Increased public education about correct food storage and aflatoxin hazards must be a priority. Link to paper

Friday, 12 August 2011

Yeast as a Universal Antifungal Vaccine?

We mentioned a few weeks ago that a research group in the US was working on a vaccine to help prevent aspergillosis. This is an alternative to attempts to identify and isolate specific antigens on the Aspergillus fungus which might form a viable basis for a vaccine that specifically prevents infection by Aspergillus. Developing specific vaccines is a long process and although they are very precise and well worth the time and effort it takes to make them there will be a long delay before they are available.

Liu et. al. set out to test which pieces of Aspergillus were most suitable to act as a vaccine by cloning them into yeast, but then realised that the yeast controls without any cloned Aspergillus were acting as a good vaccine!
To use killed yeast as a vaccine could be available relatively quickly as it is far simpler to achieve than a specific vaccine and already has a good safety record with regard to toxicity.

The researchers have shown that using yeast as a protective vaccine works well against aspergillosis in a mouse model system, so we must assume that a component of yeast is so similar to Aspergillus (both are of course fungi) that it stimulates our immune system in the same way as Aspergillus. Work so far indicates that the important components are cell wall components glucan and mannan.

Other fungi share these cell wall components so we seem to have the makings of a pan-fungal vaccine that would be useful for a wide variety of fungal infections.
What would normally happen now is that the component of the heat killed yeast that is active in providing a protective effect would be isolated and subcloned, but in this case the crude preparation is already known to be safe and lacks toxicity so the possibility remains that the crude preparation could be used as a rapidly available vaccine to provide protection against aspergillosis and a variety of other fungal infections - a remarkable discovery if hopes are borne out.

Wednesday, 10 August 2011

NewsBite: Immobilization of Aspergillus oryzae β galactosidase on nanoparticles

A demonstration of the immobilization of Aspergillus oryzae β galactosidase on native zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO-NP) by simple adsorption mechanism. Useful for a wide variety of applications in constructing enzyme-based analytical devices for clinical, environmental and food technology (biosensors).

Friday, 5 August 2011

Collaborative Cross Mice and Mapping Susceptibility to Aspergillus fumigatus

The ability of a pathogen to infect one of its hosts involves complex  interactions between the two parties. The host organism can bear genetic propensities to be resistant or susceptible to the infection and this can take many different forms, some known and some not. Unfortunately in natural populations each individual differs from other individual - this is the primary mechanism that protects every species from attack by pathogens as if an infection rapidly spreads through a population the chances are that it will not be able to infect every individual - some will be resistant.

Why aren't all individuals resistant? One reason is that it would be very costly in terms of energy or other resources for any organism to carry all 'resistance genes', and of course it is not able to predict which organism will attack & how it will attack so effectively it is unable to know which gene is likely to confer resistance. One illustrative example is the genes that confer resistance to malaria in humans. Recessive genetic differences that make the host resistant to malaria also make the host likley to produce double recessive offspring that have a crippling blood disorder - the positive finely balances the negative.

One model of choice for investigating these genes is the mouse. Over many years laboratory mice have been bred that are very close to being genetically identical. These represent the living 'blank canvas' on which to study isolated groups of genes. If all of the genes of the mouse are the same except for a small group it is possible to ignore the unchanging gene effects - this is a way to study the effects of several gene differences at once in the same mouse line. This is thought to be the next step after years of looking at single genes changes in the mouse.

This paper uses this technology to identify genes in the mouse which are important for resistance and susceptibility to aspergillosis. 371 mice from 66 separate lines were tested for resistance to Aspergillus fumigatus using a well established pulmonary infection protocol. Survial times were assessed and found to vary significantly between the lines, indicating that some loci conferred resistance better than others.

The authors were able to further narrow down the indicated loci to suggest several candidate genes conferring resistance to infection. Irf2 (Harada et al. 1989; Masumi et al. 2009) which is involved in host reposnse to infection, Laptm4b (Kawai et al. 2001) which is a transmembrane protein, Hrsb12 (Samuel et al. 1997) which is a heat responsive protein.

This demonstrates the power of this approach and more specifically indicates several novel targets for research into aspergillosis.

Monday, 1 August 2011

Steph Smith Award goes to Sally Michie

Sally Michie (23) of Aberdeen has followed a lifelong ambition to work with children and her commitment to education saw her receive the Steph Smith Award for 2011.
The award was created in memory of University of Aberdeen BEd student Steph Smith, from Nairn, who died in April 2009.

It is presented to the fourth year student on the Bachelor of Education course recognised by peers and tutors as exemplifying excellence in their values and commitment to community learning, life and laughter.  

Sally was presented with the award by Steph’s parents. She said: “I felt privileged to receive such a special award and I’ll never forget that day. It meant a lot that her mum and dad presented the award. It’s so important to keep her memory alive.  I was overwhelmed and it was a very emotional day.”

While studying for her degree, Sally, a former Oldmachar Academy pupil, was also working for the charity Voluntary Service Aberdeen (VSA) to support autistic children.
She plans to teach in Aberdeen and will undertake her probationary year at the city’s Braehead Primary School.

She said: “My heart has always been working with children and I’m so excited to begin my probationary year at Braehead in August.”
Sally will be graduating, with a 2:1 degree classification.

Steph's mum Liz speaking about her daughter to the Aspergillosis Support Group, Edinburgh

NewsBite: New Rapid Diagnostic Technique Successful in Tests

In diagnosis of invasive aspergillosis speed is essential so that appropriate treatment can begin with minimal delay. In this paper a new pan-Aspergillus rapid PCR test passed its first assessments with flying colours and is a step closer to being validated for clinical use.

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