Exploring and Exploiting Chemical Interactions in the Microbial World
Speaker: Thomas Böttcher (University of Vienna)
Host: Heike Brötz-Oesterhelt (CMFI)
Lecture Hall 3M07, Geo- und Umweltforschungszentrum (GUZ)
Our research group investigates chemical interactions of human commensal and pathogenic microorganisms with the aim to exploit these molecules as customized antibiotics against infectious diseases and to develop strategies to selectively interfere with behaviors that contribute to bacterial virulence. I will here present our recent advances in the field of the synthesis and quantification of quinolone derivatives produced by Pseudomonas aeruginosa and Burkholderia species as well as their effects on other species of the human microbiome. We demonstrated for example highly selective effects of 4-quinolone-N-oxides as bacterial weapons against Staphylococcus aureus and highlight the swiss-army knife-like nature of producing a cocktail of structurally similar but functionally distinct quinolone metabolites. I will also highlight our recent advances in generating chemical tools to modulate and control the biosynthesis of bacterial quinolones. We have demonstrated the utility of this profiling strategy by screening inhibitors of the quinolone biosynthesis enzyme PqsD and HmqD of Pseudomonas aeruginosa and Burkholderia. Chemical probe strategies have also been useful to aid the isolation and disovery of new bacterial metabolites, for example bacterial inhibitors of the proteasome. Finally, I will present ongoing work on small molecule control of the induction of latent bacterial viruses (prophages). We have demonstrated that metabolites of one species can influence the lysogeny-lysis decision switch of a prophage residing in another species, giving insights into a new form of interspecies competition.