The fast approaching post-antibiotic era has focused efforts on the search for new classes of antimicrobial compounds to arrest the increase in mortality levels attributed to microbial infections. Key to this has been the realisation that persistent infections arise from changes in polymicrobial communities, and the interactions between the protagonists within these communities can markedly affect the effectiveness of antibiotic-based interventions. Understanding the impact of key interactions within these ecosystems is key to priming the effectiveness of drug-based interventions.

We are pursuing a chemico-biological approach to investigate the molecular mechanisms underlying the anti-infective activity of small molecules from microbe-host interactomes. Evolved through co-existence, these novel molecular entities offer an effective means of pathogen control through a form of ‘chemical messaging’. Accessing the thesaurus of microbial messaging through rational design has led to a suite of distinct bioactive frameworks that can influence inter-species behaviours, moderating chronic and acute phases of virulence and pathogenesis in and other pathogens. Similarly, at the interkingdom level, small molecular entities with anti-inflammatory and anti-cancer activities have been identified. Elucidating the molecular mechanisms underpinning the bioactive potential of these small molecules is key to unlocking their potential to deliver next generation medicines. This can only be done with a deeper understanding of the pathoadaptive phenotypic and genotypic heterogeneity that is emerging from clinical studies.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.

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