Mechanical feedback promotes bacterial adaptation to antibiotics

Abstract

To maximize their fitness, cells must be able to respond effectively to stresses. This demands making trade-offs between processes that conserve resources to promote survival, and processes that use resources to promote growth and division. Understanding the nature of these trade-offs and the physics underlying them remains an outstanding challenge. Here we combine single-cell experiments and theoretical modelling to propose a mechanism for antibiotic adaptation through mechanical feedback between cell growth and morphology. Under long-term exposure to sublethal doses of ribosome-targeting antibiotics, we find that Caulobacter crescentus cells can recover their pre-stimulus growth rates and undergo dramatic changes in cell shape. Upon antibiotic removal, cells recover their original forms over multiple generations. These phenomena are explained by a physical theory of bacterial growth, which demonstrates that an increase in cell width and curvature promotes faster growth under protein synthesis inhibition. Shape changes thereby make bacteria more adaptive to surviving antibiotics. Certain bacteria cells respond to the stress of long-term exposure to antibiotics by changing their shape. Single-cell experiments and modelling cast this as a mechanical feedback strategy that makes bacteria more adaptive to surviving antibiotics.