CHEMICAL ECOLOGY - Can be defined as the chemical exploration of natural molecules (natural products) that influence behavior within or between species, genera, phylla or even Kingdoms.
For example, sex, trail, alarm or aggregation pheromones can drive behavioral responses between members of the same species, in turn delivering a valuable survival advantage. On occasion the same chemical can exert contradictory responses across different species. For example, the alarm pheromone of the Australian meat ant, Iridomyrmex purpureus, is also a selective attractant for the spider Habronestes bradleyi, a specialist predator of meat ants. In this instance, the alarm response elicited a defensive posture that protected the nest, while the attractant response lead to the death of a handful of individual ants – on balance the pheromone enhanced nest (species) survival. Chemical ecology plays out within and between many living organisms, including microbes, plants, insects and animals. The Capon Group seeks to explore and understand the ecological role of natural products, to gain knowledge, to develop protocols and tools, to enhance our efforts in microbial, pharmaceutical and agrochemical biodiscovery.
Our chemical ecology research can be considered against several sub-themes (see below).
Microbial. We are keen to explore microbial chemical ecology as it plays out between microbes, as well as between microbes and plants, microbes and animals, and microbes and insects.
Microbes vs Microbes: In 2014 we reported that ~10% of fungal cultivations treated with very low concentrations (0.6 ng/mL) of the Gram –ve cell wall constituent lipopolysaccharride (LPS) responded by altering the transcriptional status of biosynthetic gene clusters (BGCs) – either enhancing or accelerating the production of selected natural products, or activating the production of entirely new natural products, including new antibacterials. Similarly, in unpublished studies we established that selected microbial cultivations respond to treatment with mycelia acid, the cell wall constituent of mycobacteria, by stimulating the production of new natural products - including those exhibiting anti-mycobacterial activity. In ongoing studies we have demonstrated that co-cultivation of bacteria + bacteria, bacteria + fungi, and fungi + fungi can lead to the transcriptional activation of otherwise silent secondary metabolite gene clusters (BGCs). For example, we documented numerous events where as a result of co-cultivation, a chemical cue produced by microbe A activated the transcription of otherwise silent defensive natural products in microbe B. On other occasions this chemical dialogue was more complex, with the activated defensive chemical(s) from microbe B acting as a secondary chemical cue, inducing a counter defensive response by microbe A. Our efforts to detect, identify and operationalize the routine use of microbial chemical cues to activate microbial silent BGCs has the potential to inform innovative new strategies for microbial, pharmaceutical and agrochemical biodiscovery.
Microbes vs Plants: In an unpublished (confidential) collaborative study we demonstrated that bacteria isolated from the rhizosphere of plants are stimulated by the presence of a plant pathogen to produce a chemical cue that induces a biochemical change in pathogen cells, leading to the release of a secondary chemical cue that stimulates the plant innate immune system – thereby fighting off infection. Building on this discovery, we successfully synthesised the primary bacterial and secondary pathogen chemical cues, and demonstrated that pre-treatment of either soil or seedlings with the former defends against infection. We are currently exploring the scope of this discovery against an array of plant pathogens, prior to patent protection.
Microbes vs Animals: In yet another unpublished (confidential) study we recovered bacterial and fungal isolates from sheep feces and pastures heavily infected with livestock nematode parasites, and demonstrated that selected cultivations respond to parasite chemical cues leading to activation of silent BGCs and the production of new anthelmintics. This discovery represents a potential paradigm shift in anthelmintic discovery that we hope to exploit, to enhance our efforts in agrochemical biodiscovery.
Microbes vs Insects: In yet another unpublished (confidential) study we isolated a fungal strain from a specimen of mud dauber wasp. Chemical analysis of this strain across a panel of cultivation conditions (the Matrix) identified conditions that produced a beetle contact sex pheromone (CA). Remarkably, CA had only previously been isolated in trace quantities from beetles, limiting its prospect for agrochemical application. Our discovery that CA was fungal in origin suggested an unprecedented “pheromonal” relationship between beetles and beetle-associated fungi. As bark beetles are a major cause of damage to plantation timbers, we are exploring the possibility that the sexual cycle of bark beetles can be disrupted in trees inoculated with our wasp-associated fungal strain. A fungal biocontrol against bark beetle infestation would be of enormous value to both native forests and plantations under beetle assault. We hope to exploit the chemical ecology between microbes and insects, to enhance our efforts in agrochemical biodiscovery.
Venom. Better known for bioactive peptides, we are exploring the natural product (small molecule) chemical ecology of cone snail, spider, centipede and scorpion venoms. To date we have isolated and synthesized a selection of bioactive natural products, and are evaluating their biological properties. Building on an interest in microbial chemical ecology, we isolated multiple taxonomically distinct bacterial strains from different species of cone snail. Surprisingly, extracts prepared from all isolates exhibit identical secondary metabolite profiles – characterized by a suite of known antifungal polyketide macrolactams. Consistent with this level of antifungal protection, all cone snail samples were devoid of fungal biodiversity. The discovery of a highly conserved chemical ecology between cone snails and associated bacteria suggests a level of co-evolution. We are currently exploring this at a genomic level.
Cane Toad. Since their 1935 introduction to northern Queensland as a failed biological control for cane beetles, the South American cane toad Rhinella marina (formerly Bufo marinus) has invaded west into the Northern Territory and across to Western Australia, and south into northern New South Wales. The ecological impact of the cane toad invasion has been profound, leading to many deaths among native predator species (e.g. lizards, snakes, crocodiles and mammals), as well as domestic pets. This assault on Australian animals and ecosystems is of great concern to the Australian public, none more so than indigenous peoples who are confronted with the poisoning of animal species and the despoiling of areas of cultural significance. Despite public and government concern, the cane toad invasion of Australia continues unabated. Disappointingly, historic cane toad control in Australia (and elsewhere) has largely been limited to the hand and trap collection of accessible adult toads, and the occasional use of barriers to impede and redirect toad movement. For a nation as vast as Australia we need more.
Our research focuses on understanding the chemical ecology of the cane toad, to identify weaknesses that might be exploited as a means of control. In this regard we have been very successful, with three very promising lines of enquiry.
Tadpole Trapping: After identifying the pheromone cane toad tadpoles use to hunt down an eat cane toad eggs, we used this knowledge to develop an tadpole attractant bait that when used in combination with a funnel trap can selectively capture and remove tadpoles from managed water bodies (e.g. dams, lakes, creeks etc…). This technology has been patented and licensed, and is currently under commercial development.
Toad Detox: Following a detailed analysis of cane toad toxin we determined that during a predatory attack pro-toxins stored within the parotid gland are co-secreted with an enzyme that rapidly potentiates the toxin. Using chemical, transcriptomic and proteomic analyses we identified and sequenced this enzyme, and went on to characterise its kinetics and substrate specificity. In exploring this phenomena further we isolated bacteria from within the parotoid gland and demonstrated they were capable of selectively degrading/biotransforming chemicals within the toxin. Knowledge we have acquired of the relationship between cane toad toxin, enzymes and associated-bacteria has the potential to inform innovative new approaches to minimising the impact of cane toads on vulnerable native predator species.
Cane Toad Challenge (CTC). The CTC is a community engagement and citizen science program aimed at raising our profile, and attracting corporate and public sponsorship/donations/grants, to support our ongoing cane toad control research. The CTC also serves as a mechanism for informing, inspiring and partnering with, and supplying tadpole attractant baits and advice direct to the public. This initiative is gaining remarkable traction, and is poised to deliver unprecedented access to cane toad control solutions, direct to the public, community organizations, industry and government agencies.
For further information on cane toads consider reading the following;
An ugly menace
Myth-busting cane toads
Chemists vs cane toads
(Engineering World, 2009, p. 22-25)
Myth busting - cane toads in Australia
(Chemistry in Australia, 2009, p. 3-6)
Use of chemical ecology for control of the cane toad?
Cane toad chemical ecology: Getting to know your enemy