Evolutionary medicine of antibiotic resistance: how to use sequential therapy to minimize drug resistance evolution?
The enormous spread of antibiotic resistance has become a major threat to global health. Evolution is at the core of this antibiotic crisis, because it is the ability of the bacterial pathogens that underlies emergence and spread of resistance. Surprisingly, evolutionary principles are only rarely used for the development of new treatment designs. Thus, the aim of this project is to apply evolutionary knowledge to develop sequential treatment protocols that should minimize bacterial adaptation and then test these protocols using experimental evolution in combination with genomic analysis and functional genetics.
Promising strategies could involve the establishment of fluctuating environments or the exploitation of evolutionary trade-offs (e.g., collateral sensitivity). The expected results will not only be of medical value but can also enhance our understanding of microbial evolution.
Collaborations with other IMPRS groups could be developed in the course of the project, including as examples the groups of Arne Traulsen, Hildegard Uecker, or Tal Dagan.
Barbosa C, Roemhild R, Rosenstiel P, Schulenburg H (2019) Evolutionary stability of collateral sensitivity to antibiotics in the model pathogen Pseudomonas aeruginosa. eLife 8:e51481.
Roemhild R, Schulenburg H (2019) Evolutionary ecology meets the antibiotic crisis: Can we control pathogen adaptation through sequential therapy? Evol Med Public Health 2019:37-45.
Roemhild R, Gokhale CS, Dirksen P, Blake C, Rosenstiel P, Traulsen A, Andersson DI, Schulenburg H (2018) Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy. Proc. Natl. Acad. Sci. USA 115:9767-9772.