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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DEFEAT (DiseasE-FreE social life without Antibiotics resisTance)

Teaser

Summary

The application of antimicrobial compounds produced by hosts or defensive symbionts to counter the effects of diseases has been identified in a number of organisms, but despite extensive studies on their presence, we know essentially nothing about why these antimicrobials do not always trigger the rampant evolution of resistance in target parasites. Fungus-farming termites have evolved a sophisticated agricultural symbiosis that pre-dates human farming by 30 million years and, in stark contrast to virtually any other organism, does not suffer from specialised diseases. I will capitalise on recent pioneering work in my group on proximate evidence for antimicrobial defences in the termites, their fungal crops, and their complex gut bacterial communities, to develop this farming symbiosis as a unique model to test three novel concepts that may account for the evasion of resistance evolution. First, the antimicrobial compounds may have properties and evolve in ways that preclude resistance evolution in pathogens. Second, resistance may only be possible towards individual compounds and not antimicrobial cocktails. Third, pathogens may only be able to successfully invade and proliferate if they bypass several consecutive lines of defence, analogous to the six hallmarks of metazoan defence against cancer development. Testing these concepts will give us fundamental insights into the remarkable success of these symbionts complimentary contributions to defence, and more broadly, clarify the forces of multilevel natural selection that have allowed long-lived insect societies to evolve sustainability in the face of continued pathogenic threats. Documenting and understanding these disease management principles is fundamentally important for several branches of evolutionary biology, and strategically important for adjusting human practices for future antimicrobial stewardship.

Work performed

We have confirmed that termite fungus combs are vastly dominated by Termitomyces, and showed that this is not driven by obligate gut passage of substrates. This points to key behavioural and chemical defences of termite or Termitomyces. This is in line with our discovery that termites avoid substrates with virulent pathogens, and that termites rapidly use soil to cover exposed fungal gardens (WP3). Cultivation efforts have allowed us to establish a series of putative pathogens to be used to test defences (WP3) and for future experimental evolution work (WP2). Gut metabolome analyses from South African species is in progress, including network analyses and caste-specific compound identifications, forming the backbone for targeted metabolome changes associated with pathogen challenges and comparative analyses across the termite subfamily (WP1). Our hypothesis that Termitomyces plays a major role in defence appears to hold true and terpenes appear to be a major player (WP1,3). With three genomes finalised, and DNA/RNA from 18 strains (8 species) sequenced, analyses are progressing as planned, and this work will be supplemented with in situ colony measurements (WP1). Gut metagenomics is also progressing, with about 60 metagenomes analysed for one termite species performed for which we have addressed vertical transmission across host generations and are in the process of characterising potentially defensive bacteria-derived secondary metabolites (WP1,3).

Final results

The project has so far generated substantial data that points to novel means of defence of monoculture farming in fungus-growing termites, in addition to elaborating on the role of key social immunity mechanisms. At this point most of the experimental work is ongoing of unpublished, but the project is well on the way to generate results that will substantially improve our understanding of defences in farming termites and beyond