News Video | Policy | GPs | Hospitals | Medical | Mental Health | Welfare | Search

 


Otago discovery aids fight on antifungal drug resistance

4 February 2014

Otago discovery aids in fight against antifungal drug resistance

A new University of Otago research breakthrough from the Sir John Walsh Research Institute is helping pave the way for novel antifungal drugs designed to overcome the world-wide problem of growing resistance to current treatments.

Fungal infections by organisms such Candida, Aspergillus and Cryptococcus play an increasingly significant role in disease. Infections such as thrush affect premature babies, the elderly, females of reproductive age, individuals with dry mouth and terminal cancer patients. They can be fatal; 1.4 million people die annually due to fungal infections made worse by co-infections with tuberculosis and AIDS or by medically-induced immune deficiency.

To date, efforts to expand the array of antifungal treatments available have been hindered by the lack of molecular-level understanding of potential drug targets and mechanisms causing drug resistance.

Now, Otago researchers led by Dr Brian Monk, and working with colleagues at the University of California San Francisco, have determined the complex structure of a key cell membrane protein involved in sterol metabolism and resistance in a yeast model. Their findings appear in the latest online early edition of the prestigious US journal Proceedings of the National Academy of Sciences (PNAS).

Dr Monk says the research team’s feat will provide new insights into mechanisms underlying fungal resistance to triazole drugs and aid in efforts to develop new broad-spectrum drugs with minimal side-effects.

“Membrane proteins in general are important molecules in cells and they also represent around 70 per cent of all drug targets. However, they are notoriously tricky for scientists to extract from cells and successfully study, so we are delighted that we have been able to do so.”

The researchers’ X-ray crystallography images of the structure reveal new features likely to be held in common with up to half of all membrane proteins, including closely related proteins that modify the action of most commonly prescribed drugs.

“They tell us how the fungal enzyme and its relatives interact with the membrane and provide important clues about relationships with substrates, inhibitors and products that have broad implications for biology, drug design and personalised medicine.”

Dr Monk notes that their success in solving the membrane protein structure parallels a similar recent achievement by Professor Greg Cook’s team in Otago’s Department of Microbiology and Immunology.

Last month, Professor Cook and colleagues published the structure of a membrane protein essential for bacteria to generate energy, a finding which opens the way to developing new classes of antimicrobial drugs. Less than 0.5% of the protein structures so far determined worldwide are for membrane proteins.

It is particularly impressive for two groups at Otago to have published such structures in 2014, which is the United Nations-sanctioned International Year of Crystallography in honour of a century of multidisciplinary contributions to humanity, Dr Monk says.

The next steps for Dr Monk and colleagues are further study of the membrane protein in several important fungal pathogens and use state-of-the-art screening technology to identify new broad-spectrum drugs that target this protein.

The newly published research was supported by the US National Institutes of Health, the Marsden Fund of New Zealand, and the Otago Medical Research Foundation. The ongoing research is supported by the Health Research Council of New Zealand.

Dr Monk’s international co-authors on the PNAS paper include Dr Thomas Tomasiak and Professor Robert Stroud of the University of California, San Francisco and Associate Professor Jeffrey McDonald of the University of Texas Southwestern Medical Center. Local co-authors include Professor Richard Cannon, Associate Professor Joel Tyndall, Dr Mikhail Keniya and PhD student Franziska Huschmann.

Publication Details:

Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer
Brian C. Monk, Thomas M. Tomasiak, Mikhail V. Keniya, Franziska U. Huschmann, Joel D.A. Tyndall, Joseph D. O’Connell III, Richard D. Cannon, Jeffrey G. McDonald, Andrew Rodriguez, Janet S. Finer-Moore, and Robert M. Stroud
www.pnas.org/cgi/doi/10.1073/pnas.1324245111

About the Sir John Walsh Research Institute:
The Sir John Walsh Research Institute (SJWRI) is one of the University of Otago’s 14 designated flagship Research Centres. SJWRI advances research and increases knowledge for the improvement of oral health in New Zealand, and provides a focus for dental research in this country. Dr Monk is a member of the SJWRI research programme “Molecular Microbiology” led by co-author Professor Richard Cannon.
http://sjwri.otago.ac.nz

ENDS

© Scoop Media

 
 
 
 
 
Culture Headlines | Health Headlines | Education Headlines

 

Christchurch: Fixing Town Hall Means Performing Arts Precinct Rethink

Christchurch City Council’s decision to spend $127.5 million fixing the Town Hall means not all the land currently designated for the city’s Performing Arts Precinct is required, Canterbury Earthquake Recovery Minister Gerry Brownlee says. More>>

ALSO:

With Hunters & Collectors: The Rolling Stones Announce New Auckland Date

It’s the news New Zealand has been waiting for. The Rolling Stones today confirmed the rescheduled dates and venues for both the Australian and New Zealand legs of their highly anticipated ’14 On Fire’ tour. Now, Frontier Touring is also delighted ... More>>

ALSO:

Flying Things: Conchords, Pretties Help BATS Fly Home

The launch of BATS theatre’s fundraising campaign has taken off – with a bit of help from their friends. And with friends like theirs… An event last night hosted by Te Radar at Wellington’s latest waterfront venue, Shed 6, featured Fly My Pretties and, in a dream-come-true scenario, Flight of the Conchords. More>>

ALSO:

Environment: Zoo’s Own Wētā Workshop Produces Rare Giants For Release

Following unprecedented breeding and rearing success, Auckland Zoo is today releasing 150 of New Zealand’s largest giant wētā, the wētā punga, onto pest-free Motuora Island in the Hauraki Gulf. A further 150 will be released onto Tiritiri Matangi next month. More>>

Girls On Film: Divergent Hits The Big Screen

n January, Catching Fire (the second film in the Hunger Games series) not only became the biggest US box office success of 2013 : it also became the first film starring a female actor (ie. Jennifer Lawrence) to top the annual domestic earnings chart since The Exorcist, 40 years ago. More>>

ALSO:

Wellington.Scoop: No Travel Sanctions For Russian Billionaire’s Superyacht

On the same day that New Zealand announced travel sanctions against selected Russians, a Russian billionaire’s superyacht berthed in Wellington Harbour. More>>

ALSO:

Mental Health: UC Researchers Believe Robots Can Persuade People To Conform

A team of University of Canterbury (UC) researchers and scientists believe robots can persuade people to conform through group pressure... ``Our results showed that robots can induce conformity but to a significantly lesser degree than humans." More>>

NZ On Air: Local Content Holds Steady At 32% Of Television Schedules

Since 1989 NZ On Air has measured local free-to-air television content. The report compares the schedules of the six national free-to-air channels, to observe trends and changes in the local content landscape. More>>

Arts Fest: 2014 New Zealand Festival A Spectacular Celebration

The New Zealand Festival welcomed the world to Wellington over 24 days (21 Feb – 16 Mar) of arts events across the city. “[current figures show] slight increase on the 110,000 tickets issued in 2012. It’s a great result.” More>>

Get More From Scoop

 

LATEST HEADLINES

 
 
 
 
Health
Search Scoop  
 
 
Powered by Vodafone
NZ independent news