Maier, Berenike | Higgins, Paul - B 08

Aggregation into colonies and biofilms can protect bacteria from antibiotic treatment. Treatment of biofilm-related infections requires a detailed understanding of the molecular mechanisms of antibiotic tolerance. This project aims at understanding how colony formation protects the human pathogen Neisseria gonorrhoeae from antibiotic treatment. We will focus on the interplay between the physical properties of gonococcal colonies and antibiotic susceptibility.

1. We will study the effect of colony formation and colony fluidity on tolerance.
   To identify molecular mechanisms that confer antibiotic tolerance, we will follow two complementary approaches.
2. We will investigate how colony formation affects genome-wide gene expression and correlate differential gene expression to tolerance.
3. We will study the evolution of antibiotic tolerance.
   In the long term, it will be interesting to investigate the interplay between antibiotic tolerance and antibiotic resistance in the gonococcal system.

According to WHO, gonorrhea is currently the second most common STI worldwide. Vaccination is not available and the probability of failure of treatment with antibiotics is rising rapidly (1). Due to its rapid acquisition of antibiotic resistance, (multi-) drug resistant N. gonorrhoeae have been termed an urgent threat by the US Center for Disease Control. Some aspects of drug resistance are understood at the genetic level, but the effect of biofilm formation and its properties on efficiency of treatment remains poorly understood. This project aims at elucidating potential mechanisms of antibiotic tolerance in gonococcal biofilms.

• Characterize the role of colony formation on antibiotic tolerance
• Determine changes in gene expression in response to colony formation and correlate them to antibiotic tolerance
• Set up laboratory evolution experiment to assess evolution of colony phenotype, tolerance, and resistance