H2020Индивидуална стипендия2021–2023

EvoSpa · Structured, not stirred: experimental evolution in programmable antibiotic landscapes

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-07-01 → 2023-06-30
Финансиране от ЕС: 174 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Разпределението на антибиотиците в тялото се изучава чрез лабораторни опити, при които бактериите се излагат на лекарства в неравномерна среда. Това помага за разбирането и предвиждането на факторите, които влияят върху развитието на бактериалната резистентност.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Structured, not stirred: experimental evolution in programmable antibiotic landscapes

Our discovery pipeline for new antibiotics is drying and resistance is strongly on the rise. How do we make the most use of our existing antibiotics whilst minimizing resistance evolution? In order to optimize therapy, we need to be able to understand and predict the different factors influencing resistance evolution. We can actually directly study this directly by using experimental evolution. Here, bacteria are exposed to antibiotics in a lab setting and resistance evolves within days to weeks - enabling the tests of the predictive value of evolutionary models. However, these experiments are typically performed in well-mixed environments, whereas antibiotics are typically highly inhomogeneously distributed inside the body. The objective of this project was to develop and exploit a new model system to study the effect of spatial inhomogeneity on antibiotic resistance evolution.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Given the looming antibiotic resistance crisis, it is imperative to understand the fundamental determinants of resistance evolution dynamics. When antibiotics are administered to a patient, imperfect drug penetration leads to a highly inhomogeneous concentration profile. In contrast, evolution experiments to study resistance are commonly performed in homogeneous liquid environments. Recently, there has been a surge of theoretical studies suggesting that spatial drug concentration gradients drastically accelerate resistance evolution as resistant mutants evade resource competition by invading drug-enriched territory. However, the effect of spatial structure on evolutionary dynamics remains unclear due to a lack of experimental assays with well-defined, inhomogeneous landscapes.Here, I propose to develop a novel experimental assay where bacteria migrate and evolve on a landscape consisting of hundreds of independently definable environments. This assay will be implemented using custom liquid handling and imaging robots to systematically program antibiotic landscapes and measure evolution on a wide range of drug environments. By combining this novel assay with theoretical modeling, I will investigate evolution in monotonous and rugged drug landscapes. Motivated by theoretical predictions that multi-drug strategies aimed at preventing resistance evolution become compromised in inhomogeneous environments, I will further investigate the effect of spatial inhomogeneity using defined multi-drug landscapes. This project will provide a unique, quantitative and systematic experimental investigation on how spatial structure affects evolutionary dynamics. Beyond bacteria evolving antibiotic resistance, the same concepts apply for tumor resistance evolution. Overall, this project will greatly advance our understanding of resistance evolution with broad biomedical implications.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAT ZU KOLN · KolnКоординаторГермания