What are Actinomycetes?

Actinomycetes are a group of gram-positive microorganisms some of which can produce unique bioactive compounds. These micro-organisms are found in a wide range of aquatic and terrestrial environments and when, faced with harsh conditions have the ability to activate the metabolic pathways that ensure their survival. The unique bioactive compounds which may be produced through this process may have commercial applications.

History and Background.

Historically a large percentage of the world’s antibiotics have been found initially in a group of micro-organisms known collectively as actinomycetes. Anti-cancer agents and other interesting bioactive compounds have also been detected in actinomycetes. Currently throughout the world there are a series of institutes and a number of companies devoted to the commercialisation of bioactive compounds from actinomycetes. The fields of application for these bioactive compounds or the actinomycetes range from human and veterinary antibiotics through to bio-remedial processes. Recently with the advent of wide ranging antibiotic resistance to presently available antibiotics there is a resurgence in the search for new antibiotics in clinically important bacteria, especially in actinomycetes. This is of particular importance due to the increasing occurrence of virulent infections in hospitals worldwide.

The company has isolated 2 actinomycetes [streptomycetes] (isolates) that produce bioactive compounds which show significant antibiotic activity against “Superbug” Methicillin Resistance Staphylococcus Aureus (MRSA) also known as Golden Staph and Vancomycin Resistant Enterococci (VRE) bacteria.

During 2006 the multinational company Merck Sharp and Dohme reported, in the scientific journal, Nature, on the discovery of a new antibiotic that has the ability to disrupt fatty acid metabolism in bacteria. This represents a discovery of a completely new mode of action for antibiotics. The source of this antibiotic was the result of the isolation of a new actinomycete from Merck Sharp and Dohme’s large scale isolation programmes for actinomycete detection from the environment at large. This illustrates the continuing potential for the discovery of new antibiotics.

In the early 1980s one of the Company’s directors, Associate Professor David Keast, undertook what was probably and still is the largest study in Western Australia on Australian soil actinomycetes. One of the original reasons for that study being developed in Australia was the fact that its large landmass provides for a wide range of climatic variables including the unique dry sclerophyll forest environments of the south west of Western Australia. During the course of the study which had its basis in locating actinomycetes that might produce unique antibiotics, many isolates, mainly streptomycetes, were collected over a period of 3-4 years and some 12-20 different varieties were identified. The study also identified a wide range of isolates producing interesting bioactive compounds having properties such as antifungal activity. None of the isolates identified by the study were retained in Western Australia.

Actinomycetes samples often come from the soil. Western Australia is well know for its diverse set of flora and fauna, which influence evolution of unique actinomycetes.

The study provided crucial information and expertise to the scientific community about Australian soil actinomycetes and their biology. It provided information about the varieties of actinomycetes present in soils ranging from the tropics to the south west of Western Australia, the most likely sites within the soil at which they could be detected, plant species focal sites and the effects of climate change on their chances of detection and recovery. It is this basic information about Australian soil actinomycetes which the Company is utilising in its research programmes. This work has been published in a series of scientific papers in international journals.

The Company’s Projects.

Actinogen has recently discovered a completely new way to produce pure Anacardic Acid, currently offered by others for sale at around $1,000.00 per gram!

Anacardic Acid has many varied uses such as in anti-corrosives and new potential growing uses in the nanotechnology area.

The company has lodged provisional patents and/or had significant results for new anti-fungals, antibiotics and bio-degradation of plastic and paper, as well as research in the areas of new organic dyes and extracting metals from ores. 

Equally exciting is that we are also now moving to commercialise a range of biodegradable nappies and other products, containing actinomycetes that should biodegrade much faster than current products. THE GLOBAL MARKET FOR DISPOSABLE NAPPIES ALONE IS ESTIMATED IN EXCESS OF $25 BILLION.  CURRENT DISPOSABLE NAPPIES REPRESENT A LANDFILL AND ENVIRONMENTAL PROBLEM.  They are believed to sometimes take centuries TO BREAK DOWN IN LAND FILL.  Even current biodegradable plastic bags, paper and packaging products without bioactives added, may still take centuries to break down.  We believe this has inhibited the widespread take up of biodegradable products.  With Actinogen eco-friendly actinomycetes included in products in the future this could change very dramatically.

Other Projects

The Company has commenced research into the detection and isolation of soil actinomycetes found in the Western Australian environment and the Company intends to become a forerunner in this field in Australia. The Company believes that this is an exciting concept in the field of biotechnology in Australia. The Company is directing its efforts to the isolation of actinomycetes by selection techniques developed by the Company and using the isolates to locate, through selective screening processes, those producing biologically active compounds of potential medical, agricultural and industrial significance. The isolates are then broadly classified and catalogued. Site histories from soil sampling are also maintained in order that repeat sampling can be easily carried out if apparently unique bioactive compounds are identified from a particular site.

The Company intends to partially characterize bioactive compounds that have the potential for use as antibiotics directed specifically against the clinically important Methicillin Resistant Staphylococci Aureus (MRSA) and the Vancomycin Resistant Enterococci (VRE) bacteria and/or as antifungal agents specifically directed against clinically important Candida yeasts and Taphrina deformans. DNA sequencing techniques will provide more precise information on the genera and/or speciation of the selected organisms. These compounds and their source actinomycetes will then either be offered for sale or the Company will seek to enter into joint venture programs with other companies for the proving and seeking of commercial applications.

The company has identified a series of isolates that are capable of tolerating saline solutions that may have application for the rehabilitation of salt affected soils.

The Company also intends to actively seek specific cooperative programs by approaching companies with industrial and environmental problems which might be suited for rectification by actinomycetes from the Australian environment.

Several of the Company’s screening techniques have widespread application. For example, the Company has developed a “Bench Manual” for the detection and isolation of unique bioactive compounds. This manual provides for the practical requirements for the detection and isolation of unique bioactive compounds which includes initial soil sampling techniques, isolation procedures and specific screening tests to locate actinomycetes with the required characteristics.

The Company has established an arrangement with the PathWest laboratories at the QE II Medical Centre, Sir Charles Gardiner Hospital, Shenton Park, Perth, Western Australia, to utilise laboratories and equipment for carrying out its research into the detection and isolation of the desired actinomycetes and their bioactive compounds.

The bench protocols are now well established and the Company has isolated 2 actinomycetes [streptomycetes] that are producing significant antibiotic activity against the Methicillin Resistant Staphylococcus Aureus (MRSA) and the Vancomycin Resistant Enterococci (VRE) bacteria.

The Company has also identified a series of isolates which produce bioactive compounds that are active against clinically important fungal infections and some common agricultural diseases.

Currently the Company’s initial screening assays are simple and rapid to perform. Using these techniques the Company’s laboratories can screen between 100-200 actinomycete isolates a day as required.

Any actinomycetes that appear to be producing antibiotic and/or antifungal activity against the Company’s target organisms are then screened against a panel of 10 further MRSA bacteria with a wide range of antibiotic resistance patterns and also against a panel of 10 Candida yeasts of clinical importance, some of which are resistant to currently used antifungal chemicals.

Actinomycetes that prove to be active against these panels are then moved to the second level of the Company’s screening program. In the second level of the Company’s screening program the identified active actinomycetes are grown in liquid cultures and their supernatants tested for the excretion of antibiotic activity. The stability of the bioactive compounds produced are tested at room temperature, +4C, -18C and -80C over time.

The Company has commenced research into the detection and isolation of soil actinomycetes found in the Western Australian environment.

The supernatants are also screened for bacteriostatic and fungiostatic properties as well as bactericidal and fungicidal properties.

The Company intends to conduct further tests using liquid chromatography and centrifugal analysis to determine if more than one bioactive compound is present in the supernatants. Preliminary molecular weight analyses of the identified bioactive compounds will also be determined.

In the future the Company intends to conduct in vitro and in vivo tests to obtain information on toxicity and intestinal absorption of the identified bioactive compounds. Any compounds that successfully pass these tests will then be reproduced in quantities large enough for

chromatographic purification and structural analysis.

Concurrently with these tests a more detailed analysis of the actinomycetes producing the bioactive compounds will be carried out. A wide range of biochemical substrate analyses will be conducted along with DNA sequencing to better delineate the classification of the actinomycetes under test.

The Company also has the capacity to test for the ability of actinomycetes isolated from West Australian soils to digest 3 types of plastic currently in use in the domestic market and to screen for the capacity of the actinomycetes to tolerate different concentrations of saline. Salt tolerant actinomycetes form a separate sub library of microorganisms which may be of use in the rehabilitation of salt affected soils.

Other Applications.

In addition to the specific activities described above there are numerous potential commercial applications for the bioactive compounds that may be identified by the Company through selective screening techniques.

Those applications include other antibiotics and anti– fungal, anti-viral and anti-cancer agents.

It is anticipated that the Company’s screening techniques may be extended to identifying micro-organisms that have application for bio-remedial control of environmental and mining pollutants. Examples include microorganisms that may digest various sources of cellulose, domestic wastes, toxic chemicals in polluted ground or water, plastics and the treatment of salt affected soils.

The Company intends to partially characterize bioactive compounds that have the potential for use as antibiotics.

Other potential applications for actinomycetes and the compounds which they produce may include the concentration and extraction of various metals in the mining industry, the discovery of new fluorescent dyes for paints and colour directed pH indicators, the discovery of new methods of production of amino acids and the discovery of new sunscreens.

Recent developments by other researchers unrelated to the Company have led to the discovery of bioactive compounds produced by actinomycetes which are capable of alleviating clinical conditions such as blood clots and obesity in humans.