Bottlenecks, population dynamics, and antibiotic resistance evolution

• Applicant: Ernesto Berrios, Ph.D.
• Subject Area: Bioinformatics and Theoretical Biology ; Evolution, Anthropology ; Microbial Ecology and Applied Microbiology ; Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 512851323

The emergence and spread of antibiotic resistance have become a global threat to human health. Over the past few decades, this phenomenon has driven different experimental and theoretical studies aimed to prevent or delay its emergence. These studies commonly focus on comparing the efficacy of treatment strategies under a specific set of conditions. To date, however, the influence of population bottlenecks is usually not assessed, even though they are known to occur in vivo and even though they are also known to affect evolutionary dynamics.Population bottlenecks are events that drastically reduce the size of a population. Bacterial populations, in particular, undergo several bottlenecks during infection of host populations, imposed by the transmission of pathogens between hosts, the host immune system, or the antibiotic treatment employed. Despite the relevance of bottlenecks in antibiotic resistance evolution, their combined effect along with features commonly encountered in infections has been largely ignored. This proposal will contribute to filling this current, critical knowledge gap. To achieve this, I will first focus on a mathematical model to assess experimental data from my prospective host group, the Schulenburg group (Aim 1), and subsequently, expand the model to obtain a generalised understanding of the influence of bottlenecks on resistance evolution that can also be applied to clinical conditions (Aims 2 and 3). Thus, my project will address the following three main aims:Aim 1: study the combined effect of bottleneck size and antibiotic-induced selection. Here, I will fine-tune the mathematical model using the available experimental data from the Schulenburg group in order to explore how exactly bottlenecks affect the dynamics of resistance evolution.Aim 2: assess the combined effect of periodic bottlenecks and intraspecific resource competition on mutants resistant to multiple drugs. I will study how resistance is affected by homogeneous and heterogeneous competition. I will also explore the effect of taking into account the stochasticity of the population growth and bottlenecks.Aim 3: explore how bottlenecks that occur at random affect antibiotic resistance evolution. I will study how antibiotic resistance evolution is affected by coupling the bottleneck timing to the population size and determine how they influence the spread of new infections in host populations.

• DFG Programme: WBP Position