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Microbiology Australia Microbiology Australia
Issue 2




Vertical Transmission, May 2010
Science Meets Parliament was held as usual in early March and ASM again sponsored two of our members to attend. This year it was Glen Ulett, The Queensland Branch Chair and Gabrielle Belz from Victoria. They will report in the next issue of Microbiology Australia on why they found the experience to be useful and positive.
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Biodiscovery and industrial applications of microbial resources
This issue of Microbiology Australia focuses on an aspect of microbiology increasingly becoming important to us microbiologists – the applied and industrial microbiology. The majority of microbiologists in the global context are in the business of dealing with the challenges that microorganisms bring to society involving processes and products that are of major economic, environmental and social importance. These include production of valuable microbial products via fermentation processes such as fermented foods, beverages and dairy products as well as direct application of microorganisms or their products in environmental and biotechnological operations. In addition, over the past 20 years, many traditional and established industrial fermentation processes have advanced through the contribution of genetic engineering, which has facilitated the development of many novel processes and products.
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Biodiscovery from microbial resources: Actinomycetes leading the way
Biodiscovery from microbial resources can be defined as the exploration of microbial metabolic products to detect, identify and evaluate their potential for medicinal, agricultural and biotechnological operations. Microbial resource centres house microbial compounds produced under different physical and nutritional parameters to maximise the production of metabolites and are subsequently tested in different bioassays to define targeted activity.
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From discovery to commercialisation of vaccines
Having spent the first 25 years of my [IG] working life involved in research on vaccine development and delivery and then a decade in industry, working for and with, companies that actually made vaccines, I am reminded of the observation, attributed to Charles Dickens: "When I was 14, I thought my Father was the stupidest person on earth. When I was 21, I was amazed at how much he had learnt in the past 7 years." Exposure to the harsh realities of product development challenged my academic preconceptions, gave me a greater insight into the nature and complexity of the development process and a greater respect for the skills of those involved.
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Endophytes and the microbial genetics of traditional medicines
Traditional medicine continues to play an essential role in the healthcare systems of many cultures. In some Asian and African countries up to 80% of the population depend on these ancient and culturally based medicinal practices for their primary healthcare needs. Plants and their derived natural products are frequently employed as traditional medicine and such plants are viewed as attractive targets for the discovery of novel therapeutic agents in natural product investigations. A variety of useful drugs has been discovered following the investigation of traditional herbs, such as morphine (analgesic), digitoxin (cariotonic) and ephedrine (sympathomimetic). These ethnopharmacology approaches to drug discovery are based on the premise that plants used as traditional medicines have shown some form of bioactivity and have the increased likelihood of containing bioactive compounds in comparison to plants selected at random. Three systems of traditional medicine that are relevant to Australian drug discovery researchers include the Chinese, Australian Aboriginal and Indonesian systems.
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Searching for the dengue virus Achilles heel
Dengue viruses are a major public health problem throughout the tropical world, with up to 100 million people infected annually. Infection can result in acute febrile illness (dengue fever) and in severe cases is associated with abnormalities in vascular permeability and haemostasis (dengue haemorrhagic fever) that can lead to sudden and fatal hypovolemic shock (dengue shock syndrome). The incidence of dengue has steadily increased over the last two to three decades such that it is now endemic throughout much of the tropics and is the leading cause of infant mortality in some South-East Asian countries. Australia has not escaped this territorial expansion of dengue, with regular epidemic outbreaks now occurring in North Queensland. The epidemic that lasted for most of the summer of 2008–2009 involved the circulation of all four dengue virus serotypes and more than 1,000 confirmed cases. Coupled with the potential impact that climate change may have in increasing the range of its mosquito vector, there is growing concern that dengue may become endemic in Australia. Considerable challenges have accompanied the development of vaccine strategies for dengue and this has reinforced the importance of the complementary development of antiviral therapies. Part of our dengue research efforts has been focused on identifying viral targets for inhibitor design.
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Bacteriophages as tools in drug discovery programs
Screening of microbial natural products continues to represent an important route to the discovery of novel bioactive compounds for the development of new therapeutic or other important industrial agents. However, a continuous supply of diverse compounds is needed to meet the needs of industry. Such a supply can only be derived through systematic screening of bioactive compound-producing microorganisms from natural sources.
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Queensland is not just a beautiful place to live and visit. Behind the beauty is unparalleled biodiversity, unique tropical expertise and unsurpassed opportunities. Nowhere else on earth has such rich potential when it comes to our rainforests and reefs as sources of new drug discoveries. In Queensland we are proud of our natural assets and want to ensure biodiscovery is carried out in a sustainable manner. In 2004, the Queensland Government introduced best-practice legislation to create legal certainty for biodiscovery activities in the State. The Biodiscovery Act 2004 (Qld) provides sustainable access to Queensland’s biodiversity and fulfils Queensland’s commitment to Article 15 of the international Convention on Biological Diversity.
 
 

Australian microbial biodiscovery: from bugs to drugs
To maintain and improve the quality of life offered by modern healthcare requires an ongoing commitment to the development of new drugs, to improve and replace those that have become less effective, and to bring to the community safer treatments for an ever-wider array of important diseases. Irrespective of the specific medical need, the drug discovery pipeline is critically dependent on access to diverse, high-quality molecular libraries capable of inspiring drug-led discovery, and ultimately new drugs. A poor choice of chemistry leads to wasted resources and no drugs. Historically the pharmaceutical industry has relied heavily on microbial natural products, which represent an extraordinarily diverse, preassembled pool of biologically active molecules, programmed to be potent and selective modulators of key biopolymers, cells, tissues, organs and animals. Knowledge of Nature’s intellectual property, gleaned from the evolutionary equivalent of a billion-year global drug discovery program, with an unlimited budget and a workforce of trillions, can disclose privileged bioactive structures that inform, guide and inspire modern drug discovery, re-purposing ecological advantage to pharmaceutical benefit.
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Large-scale recombinant protein production and structure-based drug design capabilities at CSIRO
CSIRO has opened its large-scale Recombinant Protein Production Facilities (RPPF) as part of the National Collaborative Research Infrastructure Scheme (NCRIS).
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Biofuels: the next generation
There are many issues with the continued use of fossil fuels for energy, including finite supply, energy security and their contribution to rising atmospheric CO2 concentrations and climate change, leading to substantial, increased interest in the research and development of renewable energy. In 2006, renewable energy provided only 2.5% of global energy needs, which is well short of the national renewable energy targets of many countries for the period 2020-2030, including Australia. For these reasons there is substantial investment in the development of renewable fuel technologies. Bioethanol and biodiesel derived from biomass are alternative fuels for which production capacity and demand is rapidly increasing.
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Mitochondria, oxidative stress and the petite phenotype in Saccharomyces cerevisiae
Oxidative stress has long been recognised as biologically important and is increasingly implicated in a variety of phenomena, such as mutation, carcinogenesis, degenerative and other diseases, inflammation, ageing, and development. The role of the mitochondrion in oxidative stress and the production of reactive oxygen species (ROS) and other radical species is well-established, with mitochondria providing a fascinating area of study within the oxidative stress field. Mitochondria are essential organelles for the viability of all eukaryotic organisms. While mitochondria perform important processes associated with oxidative phosphorylation and energy production, and numerous other metabolic processes, such as iron sulfur cluster biogenesis, lipid and amino acid synthesis, they also appear to be the largest intracellular source of ROS in aerobic cells. The steady state concentration of O2 in the mitochondrial matrix is five- to tenfold higher than in the cytosol or nuclear space according to one estimation. Therefore, mitochondrial macromolecules such as mitochondrial DNA are particularly susceptible to oxidative damage.
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Biodiscovery of chemo preventatives of Alzheimer’s disease using yeast
Yeasts have been used as models for just about everything, from basic studies in molecular biology and genetics to cancer and studies of drug resistance. Initially Alzheimer’s disease (AD) was seen as an extracellular disease, so it was hard to see how yeast might make a contribution to AD research. However, there is now recognition that the main player, A?, has intracellular and extracellular effects. Furthermore, it is now clear that yeast studies are relevant to AD.
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Generating interspecific wine yeast hybrids for funky wines
When we think of Saccharomyces cerevisiae, fermentation immediately comes to mind, but this is not the only trait that makes this yeast the organism of choice for bread, beer and wine production. The winemaking industry, for example, requires robust strains, capable of converting sugar to ethanol in challenging conditions; high osmotic stress and low pH in the initial grape must, followed by high ethanol concentration at the later stages of fermentation. Winemakers also look for ways of using fermentation to introduce aroma and flavour diversity to their wines as a means of improving style and for product differentiation. Choice of wine yeast from the plethora of strains available to winemakers is one way of achieving this, particularly with the new breed of interspecific hybrid yeast strains currently being generated.
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Salmonella in food products – a vector for distribution of antibiotic resistance
Non-typhoidal Salmonella spp. are common food-associated pathogens, and Salmonella infections are one of the most common causes of death associated with food-associated illness, especially in developing countries. As in many other developing countries, raw food hygiene and antimicrobial resistance epidemiology are in their infancy in Vietnam. In addition, the lack of stringent controls on antimicrobial usage in human health and particularly in animal production systems increases the risk of food-borne pathogens harbouring and disseminating antibiotic resistance genes. For countries such as Vietnam, Thailand and other Asian countries, Salmonella vaccination is a more cost-effective way of controlling Salmonella in food production animals than the use of antibiotic therapy.
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Fungal phospholipid metabolism for antifungal drug discovery
Invasive fungal infections often respond poorly to antifungal drugs. The fungal invasin phospholipase B (PLB) and/or its biosynthetic pathway are novel targets for drug development. Compounds with structural similarities to phosphatidylcholine, which is a preferred substrate of cryptococcal PLB1, were purchased or synthesised. For many, there was a correlation between antifungal and anti-PLB activity but not all demonstrated selectivity for fungal compared with mammalian phospholipase, and some were toxic to mammalian cells in culture. The most promising, a bis-pyridinium compound, is undergoing toxicity testing in mice. Miltefosine (MI), a stable phospholipid analogue used in the treatment of leishmaniasis also has broad spectrum fungicidal activity, but inhibition of PLB is not its major mode of action. To improve antifungal potency and reduce toxicity of MI, analogues of this alkyl phospholipid have been synthesised and are under investigation.
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Victoria taking biotechnology from strength to strength
Victoria is Australia’s leading biotechnology location, with strengths in cancer, neuroscience, stem cells, infectious disease and immunity, and agricultural biotechnology. With its clusters of world-class universities, teaching hospitals, research institutions and industry, the state continues to advance in its aim to become one of the top five biotechnology locations worldwide.
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A tribute to Professor Arnold L Demain – a lifetime in industrial microbiology
Professor Arnold (Arny) Lester Demain is one of the few scientists who have witnessed the progress of biotechnology in a career that has spanned almost 60 years. He is one of the world’s leading industrial microbiologists who has pioneered discovery in genetic and nutritional regulation of biosynthetic pathways leading to overproduction of a suite of primary and secondary metabolites, and their subsequent scale-up in manufacturing processes. These metabolites have huge economic value due to their application in the food, pharmaceutical and agricultural sectors. In this article, Arny’s story is summarised and put in context of the changing face of biotechnology in the various ‘golden ages’ of biotechnology. A former Rubbo Orator in 1979, Arny will be visiting Australia again in 2010 to present the closing plenary address at the Genetics of Industrial Microorganisms Symposium (GIMS) in Melbourne, a role he played before at the first GIMS in 1970.
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Past Issues

 

Volume 38

Issue 3 (September 2017)
Issue 2 (May 2017)
Issue 1 (March 2017)

Volume 37

Issue 4 (November 2016)
Issue 3 (September 2016)
Issue 2 (April 2016)
Issue 1 (March 2016)


Past Years

2010 to 2015
2002 to 2009



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Guide to Mosquitoes of Australia

Guide to Mosquitoes of Australia

Provides a comprehensive, user-friendly guide to the mosquitoes of Australia and key strategies for managing them.

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