An evolutionary perspective on antibiotic treatment and the spread of resistance

Antibiotic resistance at its core is a problem of evolutionary biology. Bacteria evolve resistance to antibiotics either through the accumulation of resistant variants or of horizontally transferred genes. The selection of these resistance determinants over 80 years of the mass use and misuse of antibiotics has resulted in their widespread dispersal, rendering many antibiotics ineffective. While a multifaceted approach is required to solve this crisis, for a sustainable solution all facets must take evolution into account. In this thesis, I approach the fields of antibiotic treatment and the spread of resistance from an evolutionary perspective.

Within this umbrella, I examine fundamental aspects of the problem such as bacterial interactions under antibiotic treatments, and drivers of horizontal gene transfer of antibiotic resistance genes. On the more translational side, I am involved in identifying principles which can help optimize evolution-informed antibiotic therapy such as rate of spontaneous resistance to antibiotics, it’s resulting cross-effects and conserved patterns of collateral sensitivity between antibiotics. To answer these questions, I combine methods in microbiology, antimicrobial susceptibility testing, experimental evolution, molecular biology, genomics, advanced statistics and insights from mathematical models.

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