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Dr. Alexandre Duprey - Beyond topoisomerases: finding and exploiting new antibiotic targets to control DNA supercoiling in bacteria

 

Alexandre Duprey

Yale School of Medicine, New Haven, CT, USA

Beyond topoisomerases: finding and exploiting new antibiotic targets to control DNA supercoiling in bacteria

Supercoiling is an essential property of DNA with numerous avenues for therapeutic applications, from anticancer drugs to antibiotics. Unfortunately, antibiotic resistance to existing classes of supercoiling-altering drugs like aminocoumarins and fluoroquinolones is widespread and increasingly difficult to overcome, to the point that no new supercoiling-altering drug has been commercialized since the year 2000. This is because all those drugs target the same enzyme (DNA gyrase). In this talk, I will present my foundational work regarding the development of a new high throughput method to measure DNA supercoiling and some potential drug targets that were found thanks to it. Then, I will introduce plans to exploit it further and discover new, unsuspected classes of antibiotics that would also be more specific to killing certain undesirable bacteria like ESKAPE pathogens, or even capable of shutting down virulence factors of pathogens without directly killing them, therefore limiting dangerous side-effects linked to dysbiosis.

Selected references

  • Duprey A & Groisman EA (2020) DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines. PLOS Genetics 16, e1009085
  • Duprey A & Groisman E (2020) FEDS: a novel fluorescence-based high-throughput method for measuring DNA supercoiling in vivo. mBio 11
  • Duprey A & Groisman EA. (2021) The regulation of DNA supercoiling across evolution. Protein Science 30, 2042–2056

Contact: Olivier Neyrolles (Olivier.Neyrolles@ipbs.fr)

Link to attend the seminar:

6 Jul

16:00 - 17:00

Online seminar