Type I toxin-antitoxin systems from bacterial pathogens

Our team focuses on the regulatory mechanisms that govern the expression of type I toxin-antitoxin systems (T1TAs) from pathogenic bacteria. These systems are composed of an antibacterial toxin and a complementary small RNA antitoxin that can prevent the translation of the toxin coding mRNA. Due to their potent killing activity, the production of these toxins is tightly controlled at many levels. We aim at understanding the regulation mechanisms and activation pathways of type I toxin-antitoxin systems. To this end, we are using a recent technique, a genetic screen combined with deep-sequencing. This precise characterization is crucial to ultimately hijack these systems for the development of novel antibiotic strategies. Compared to traditional antibiotics, the activation of type I toxins will allow to target only specific bacteria without affecting the commensal flora, thus hindering the emergence of antibiotic resistance.

Topics

  • Identification of novel toxin-antitoxin systems in bacterial pathogens
  • Post-transcriptional regulation
  • Maturation of bacterial RNA 5′ and 3′ ends
  • Characterization of toxin-antitoxin activation pathways

Approaches

  • Molecular microbiology
  • Bacterial genetics
  • Biochemistry
  • Next-generation sequencing