Pathogen Evolution
Drug resistance evolution across taxonomic boundaries:
investigating the effects of ploidy, lifestyle, and reproductive strategy
Project background
The escalating threat of drug resistance is a global crisis. Bacteria, fungi, macroscopic parasites, and viruses are constantly adapting to evade drug treatments, leading to devastating human losses and crippling economic costs in agriculture.
Though drug resistance is primarily viewed through a human health lens, the largest volume of drug use occurs in agriculture. The One Health framework reveals the connections between human, animal, and ecosystem health. Our increasing dependence on animals strengthens this link, making the spread of pathogens – and drug resistance – more likely.
We are expanding our team!
We are looking for two PhD students and a postdoc to address the urgent issue of drug resistance evolution. One part of the project focuses on developing a large, comprehensive database of pharmacodynamic data from different sources. The other aims to develop a modular model, that would allow us to investigate important factors influencing resistance evolution: reproductive strategy, lifestyle, and ploidy. Read below!
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PhD in Pharmacodynamic Data Analysis
All positions are shared between ETH and Eawag (Swiss Federal Institute of Aquatic Science and Technology). Read more.
Pharmacodynamic database and data analysis
We aim to collect, map, and analyze the existing knowledge of pharmacodynamic data relevant for drug resistance modeling from various disciplines, from human through veterinary medicine to agriculture.
Modular model
We aim to develop a modular model, combining population genetic principles with a pharmacodynamic approach. This will allow us to investigate the role of reproductive strategy, lifestyle and ploidy.
Project Overview
This project aims to understand how different reproductive strategies affect drug resistance evolution in bacteria, fungi, and helminths. We want to take advantage of the generality of the evolutionary process while still accommodating important differences between the studied organisms. Therefore, we will develop a a modular model that can be tailored to individual species (1).
In parallel, we will extract, collect and catalog as many relevant pharmacokinetic and pharmacodynamic data as possible (2). This will allow us map the landscape of known pharmacodynamic parameter values, pointing out gaps and investigating overlaps. The mined data will be analyzed for trends and patterns, exploring their distributions and ranges, which will help us to come up with reasonable estimates of values that are yet unavailable (2).
Combining the modular model with a large amount of pharmacodynamic data will allow us to model concrete species, investigate specific scenarios, and shed light on the importance of reproductive strategy, ploidy, and lifestyle} in the studied taxa (3). In collaboration with empirical biologists studying these taxa, we will develop testable hypotheses and come up with predictions that can be verified experimentally.
In addition, we will review the literature, identifying temporal and spatial trends and patterns in drug resistance evolution in the studied taxa (4). If there are any differences in the observed trends between species, we will investigate whether these can be at least partially explained by the differences in reproductive strategy and associated aspects, e.g., ploidy or lifestyle.
We focus on drug resistance evolution in three major contributors to disease burden worldwide - bacteria, fungi, and helminths.
Bacteria
Throughout history, bacteria have caused countless fatal diseases. Yet, in recent decades, antibiotics revolutionized treatment. However, bacteria's rapid evolution, fueled by large populations and widespread antibiotic use, leads to alarming resistance, with no antibiotic being spared. We may be facing a dangerous post-antibiotic era where once-treatable diseases threaten lives again.
Parasitic worms
Helminths, especially nematodes, infect plants, animals, and humans alike. Even with advances in sanitation, they persist as some of the most common infections globally, disproportionately affecting those in poverty. The CDC estimates one billion Ascaris infections alone. Even though the diseases they cause can be fatal, they belong to the Neglected Tropical Diseases group – underfunded and often overlooked on the global health agenda.
Anthelminthic drugs are typically effective, but their overuse in livestock has led to the rise of drug-resistant strains. This resistance is a growing global problem, harming agriculture and posing a zoonotic threat with implications for One Health initiatives.
Fungi
Though less publicized than bacterial diseases, fungal infections (mycoses) are a major threat, especially fatal to immunocompromised individuals. In addition, mycoses are especially common in plants, affecting farm production worldwide, causing mass devastation of crops and threatening food security.
However, resistance to many fungicides has already emerged and spread in pathogen populations. Moreover, the time to resistance evolution has been shown to decrease: the later the drug was introduced, the shorter the time until the resistance was recorded.