Thursday, 27 June 2013

€6.1million project to develop antifungal agents to treat infections

The University of Manchester and F2G Ltd, a privately-held antifungal drug discovery and development company and today announced the start of a 6.1 million euro EU-funded project to discover and develop novel antifungal drugs to treat serious, life-threatening fungal infections.

The NOFUN project is a collaborative project under the 7th Framework Program of the European Commission which brings together five partners to accelerate the development of a number of F2G’s broad spectrum antifungal agents.

About two million people die each year because of fungal infection and resistance is rapidly emerging to the most common drugs used to treat these diseases. This project aims to develop novel agents with completely new ways of acting in order to combat the increasing tide of drug resistant fungal infections. NOFUN will use F2G’s discovery assets and the University’s fungal genomics platforms in addition to the drug development and characterisation expertise of the other partners.

Participants in the NOFUN Project are F2G Ltd (UK), The University of Manchester (UK), Pharmacelsus GmbH (Germany), OncoTargeting AB (Sweden) and Universitat i Rovira Virgili (Spain).

Dr Mike Bromley, NOFUN Project Coordinator from The Manchester Fungal Infection Group at The University of Manchester, said: “We are delighted that this project has been funded and it confirms The University of Manchester as a centre of excellence in fungal biology and disease. Hopefully this cash boost will help us to create new treatments to tackle serious, life-threatening fungal infections.”

Dr Mike Birch of F2G and Scientific Coordinator of NOFUN added: “Competition for funding in this call was immense and the NOFUN award represents a significant validation of the project and the partners. F2G is delighted to lead the scientific program to develop much needed new antifungal agents”.

Notes for editors
For further information, please contact Alison Barbuti, Media Relations Officer, Faculty of Medical and Human Sciences, 0161 275 8383, alison.barbuti@manchester.ac.uk

Wednesday, 26 June 2013

Barcoding All Life on Planet Earth


DNA Barcoding is the process of defining a short DNA sequence which is unique to a particular species. Once we have such a piece of DNA for a species we can use it to identify that species by looking for that sequence whenever we are trying to find out what species an unknown organism (or part of an organism) belongs to - rather like scanning the barcode of a product in a supermarket in order to find out what it costs and other information.

All supermarkets have tens of thousands of products that all need a unique barcode and those are provided by the manufacturer of the goods. Bold Systems are attempting to record a unique barcode for every living species on the planet - or at least every one that can be practically achieved. That is quite some undertaking as there are many millions of life forms on earth and the current count has reached over two million barcodes - there is a long way to go! The map heading this blog gives an idea of the spread of barcoded species that have already been collected.

Of the species already barcoded around 2500 are fungi.

Bold Systems are one part of this work that attempts to aid the collection of barcodes by providing access to the tools & resources needed free of charge, however there are other groups including the Consortium for the Barcode of Life





Tuesday, 25 June 2013

Aspergillus felis: new fungus found in Australia, causes infections in humans, cats

Originally posted at ProMED, this article described a new species of Aspergillus that is pathogenic to humans in a similar way to known species of Aspergillus that are pathogenic to humans - it is very rare for any infection to become established unless the human has a badly compromised immune system and is already vulnerable to all types of infection.

A multinational team of biologists writing in the open-access journal PLoS ONE has identified a new species of fungus that causes life-threatening infections in humans, dogs, and cats.
Study lead author Dr Vanessa Barrs from the University of Sydney said: "this all originated from spotting an unusual fungal infection in 3 cats I was seeing at the University's cat treatment centre in 2006."
"These cats presented with a tumor-like growth in one of their eye sockets, that had spread there from the nasal cavity. The fungal spores are inhaled and in susceptible cats they establish a life-threatening infection that is very difficult to treat.
Finally I was able to confirm this as a completely new species, Aspergillus felis, which can cause virulent disease in humans and cats by infecting their respiratory tract. We were able to demonstrate that this was a new species of fungus on a molecular and reproductive level and in terms of its form."
Dr Barrs said that similar to the closely related fungus _Aspergillus fumigatus_, "this new species of fungus can reproduce both asexually and sexually -- and we discovered both phases of the fungus."
Since the 1st sighting of _Aspergillus felis_, more than 20 sick domestic cats from around Australia and one cat from the United Kingdom have been diagnosed with the fungus.
The fungus appears to infect otherwise healthy cats but in the 2 humans identified it attacked an already highly compromised immune system.
The disease is not passed between humans and cats but its study in cats will not only help their treatment but also provide a good model for the study of the disease in people. There is only a 15 percent survival rate of cats with the disease and it has so far proved fatal in humans.
To date only one case has been identified in a dog.
"We are right at the start of recognizing the diseases caused by this fungus in animals and humans. The number of cases may be increasing in frequency or it may just be we are getting better at recognizing them."
"Fungi like _Aspergillus felis_ can be easily misidentified as the closely related fungus _Aspergillus fumigatus_, which is a well-studied cause of disease in humans. However, _Aspergillus felis_ is intrinsically more resistant to antifungal drugs than _Aspergillus fumigatus_ and this has important implications for therapy and prognosis," Dr Barrs concluded.
Bibliographic information: Barrs VR et al. 2013. _Aspergillus felis_ sp. nov., an Emerging Agent of Invasive Aspergillosis in Humans, Cats, and Dogs. PLoS ONE 8(6): e64871; doi:10.1371/journal.pone.0064871;http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0064871
--Communicated by:ProMED-mail from HealthMap Alerts
[This article indicates this is a new fungus, which does not transfer between humans and cats. The logical corollary is it does not transfer between cats and humans either, but that is not clearly stated. It may also be a discovery too new to completely understand the transfer of the fungus between organisms.

Monday, 24 June 2013

New Antifungal Drug Development Encouraged

The Food and Drug Administration (FDA or Agency) is proposing a regulation to establish a list of "qualifying pathogens" that have the potential to pose a serious threat to public health. The proposed rule would implement a provision of the Generating Antibiotic Incentives Now (GAIN) title of the Food and Drug Administration Safety and Innovation Act (FDASIA).

GAIN is intended to encourage development of new antibacterial and antifungal drugs for the treatment of serious or life-threatening infections, and provides incentives such as eligibility for designation as a fast-track product and an additional 5 years of exclusivity (when drug companies have sole rights to market the new drug) to be added to certain exclusivity periods. 

FDA is proposing that the following pathogens comprise the list of "qualifying pathogens:" Acinetobacter species, Aspergillus species, Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium difficile, Enterobacteriaceae(e.g., Klebsiella pneumoniae), Enterococcus species, Mycobacterium tuberculosis complex, Neisseria gonorrhoeae, N. meningitidis, Non-tuberculous mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus agalactiae, S. pneumoniae, S. pyogenes, and Vibrio cholerae.

Wednesday, 12 June 2013

Genomics Powering the Search for Answers to Drug Resistance

There is a small but significant chance that a patient who is treated for a fungal infection with one of the azole class of antifungal drug will have to be switched to a different antifungal as their infection becomes resistant to the first drug used. This is of course a familiar type of story as battles with bacterial resistance to antibiotics are now very familiar to us with the present of MRSA for example.

The resistance of fungi to antifungal drugs is not new but it is becoming clearer that we need to start developing new strategies to beat resistance as research results accumulate from around the world and large specialist medical centres like the National Aspergillosis Centre are able to report on research from large numbers of patients being treated with antifungals over the longer term.

Happily we are seeing the development of newer tools with which to carry out research more rapidly and one such tool is the use of rapid DNA sequencing and comparative genomics. 

In this study the researchers have compared the genomes of four strains of Aspergillosis, two that are resistant to an antifungal with two that are not resistant (a research strategy unthinkable 5 years ago as it would have been slow and very expensive). All isolates came from one patient! 

As a result they have found a new mechanism for resistance to azoles involving the gene HapE. They identified a mutation in this gene and then proved that the presence of the mutation was consistent with resistance by conducting (old fashioned but very powerful) genetic crossing experiments. When a mutated form of HapE was moved into a non-resistant strain using molecular biology techniques the resistance reappeared! This is powerful proof that a particular mutated form of HapE confers resistance - and this gene is not known to be involved in resistance up to this point in time so this may well be a new mechanism for resistance.

This is the first time that whole genome sequencing and sexual crossing strategies have been used to find the genetic basis of a trait of interest in A. fumigatus. The discovery may help understand alternate pathways for azole resistance in A. fumigatus with implications for the molecular diagnosis of resistance and drug discovery.

Tuesday, 11 June 2013

Nebulisers are a Potential Source of Respiratory Infection

Nosocomial infections (infections acquired in hospital) are a serious problem in the hospital care environment - it isn't difficult to imagine that when you are surrounded by people with serious infections there is a high chance that you could be infected by the same organism that is infecting them if thorough safeguards are not put in place to prevent this.

Despite many precautions to prevent them nosocomial infections do still occur so extensive efforts are made to detect what could be causing these problems. This recent research article investigates one such cause for respiratory infections; the equipment often used to assist breathing eg nebulizers, oxygen humidifiers and the tubing used to connect the different components together.

The investigators tested all equipment for microbial contamination in a hospital in India. Surprisingly 76% of all equipment swabbed bore Aspergillus as a contaminant and perhaps even more worryingly 87% were contaminated with bacteria. Nearly 30% of the bacteria were multidrug resistant strains.

This clearly illustrates the importance of effective cleaning of all components of this type of equipment between patients and preventing sharing! In all probability this is already standard practice in many hospitals but this research work serves to illustrate how important it is to ensure policies are in place and adhered to!



Monday, 10 June 2013

Comparing a novel Aspergillus lateral-flow device with the Platelia EIA for rapid diagnosis.

The detection of galactomannan in patient's serum is central to the diagnosis of invasive fungal infection. Any delay in diagnosing an invasive fungal infection and therefore a delay in treatment leads to a poor outcome. A recent paper has compared the performance from a novel  lateral flow device method, Aspergillus-(LFD) with the widely used Patelia® galactomannan (EIA) detection method.

Serum was tested from 101 patients after undergoing an allogeneic stem cell transplantation.By the end of hospitalisation, one proven, nine probable and 20 possible cases of invasive fungal infection were identified.
The Aspergillus-LFD showed a comparable diagnostic performance to the GM-EIA. However, if the results have to be confirmed by a second positive serum, then the GM-EIA exhibited a superior sensitivity.

Comparing the 2 methods in terms of practicability, the Aspergillus-LFD was demonstrated to be a quick (15 min) and easy-to-use test for single-patient detection of Aspergillus antigens or to rule them out, but not if more than one positive serum is required. Link



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