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Humboldt-Universität zu Berlin | IRI Life Sciences | Events | IRI Talks | Dates | IRI-Talk: Nassos Typas - Drugs & Bugs: unexplored relationships

IRI-Talk: Nassos Typas - Drugs & Bugs: unexplored relationships

What
  • Past
  • IRI Talk
When Nov 26, 2018 from 04:15 PM to 05:15 PM (Europe/Vienna / UTC100) iCal
Where IRI Life Sciences, Seminar Room 104 (Ground Floor); Philippstr 13, Building 18

Abstract:

Do drugs impact our gut residential flora, and if so is this restricted to antibacterials? Are there any general principles behind drug-drug interactions, and if so, can such principles help us identify effective drug combinations against multi-drug resistant (MDR) bacterial infections? Here I will present how systematic and quantitative approaches can give us insights into these questions.

We recently established that non-antibiotic drugs have a strong and broad impact on the human gut microbiome. This opens new paths for optimizing drug efficacy and mitigating side-effects, but also has direct implications on the spread of antibiotic resistance. We are now dissecting the collateral damage of antibiotics on the gut microbes, identifying unexpected activities and resistance mechanisms, and discovering ways to bypass this collateral damage.

At a second level, we have performed a large screen of ~3,000 pairwise combinations of different antibiotics, selected human-targeted drugs and food additives in 3 prominent Gram-negative pathogens. This has allowed us to draw conclusions on the conservation of drug interactions, identify mechanistic biases of synergies and antagonisms, and discover potent synergies that are effective against MDR pathogens.

Finally, we have adapted thermal proteome profiling (TPP) in bacteria, which allows to allows us to probe the thermostability of proteins in vivo and in vitro in a proteome-wide fashion. TPP can be used for antimicrobial target deconvolution and for mapping antibiotic resistance mechanisms. In addition, it provides unique insights into cellular physiology, including protein complex architecture and metabolic pathway activity.