4.8 Article

Mechanical feedback promotes bacterial adaptation to antibiotics

Journal

NATURE PHYSICS
Volume 17, Issue 3, Pages 403-+

Publisher

NATURE RESEARCH
DOI: 10.1038/s41567-020-01079-x

Keywords

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Funding

  1. Engineering and Physical Sciences Research Council of the United Kingdom [EP/R029822/1]
  2. Royal Society [URF/R1/180187, RGF/EA/181044]
  3. National Science Foundation Physics of Living Systems Program [NSF PHY-1305542]
  4. National Science Foundation Materials Research Science and Engineering Center at the University of Chicago [NSF DMR-1420709, NSF DMR-2011854]
  5. National Science Foundation [MCB-1953402]
  6. EPSRC [EP/R029822/1] Funding Source: UKRI

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Cells must strike a balance between conserving resources for survival and utilizing resources for growth and division in order to maximize their fitness. This study combines single-cell experiments and theoretical modeling to propose a mechanism for antibiotic adaptation through mechanical feedback between cell growth and morphology. The increase in cell width and curvature promotes faster growth under protein synthesis inhibition, making bacteria more adaptive to surviving antibiotics.
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.

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