Antibiotic Resistance via Bacterial Cell Shape-Shifting

mBio. 2022 Jun 28;13(3):e0065922. doi: 10.1128/mbio.00659-22. Epub 2022 May 26.

Abstract

Bacteria have evolved to develop multiple strategies for antibiotic resistance by effectively reducing intracellular antibiotic concentrations or antibiotic binding affinities, but the role of cell morphology in antibiotic resistance remains poorly understood. By analyzing cell morphological data for different bacterial species under antibiotic stress, we find that bacteria increase or decrease the cell surface-to-volume ratio depending on the antibiotic target. Using quantitative modeling, we show that by reducing the surface-to-volume ratio, bacteria can effectively reduce the intracellular antibiotic concentration by decreasing antibiotic influx. The model further predicts that bacteria can increase the surface-to-volume ratio to induce the dilution of membrane-targeting antibiotics, in agreement with experimental data. Using a whole-cell model for the regulation of cell shape and growth by antibiotics, we predict shape transformations that bacteria can utilize to increase their fitness in the presence of antibiotics. We conclude by discussing additional pathways for antibiotic resistance that may act in synergy with shape-induced resistance.

Keywords: antibiotic resistance; bacterial morphogenesis; drug transport; growth physiology; mathematical modeling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacteria*
  • Cell Shape
  • Drug Resistance, Bacterial
  • Drug Resistance, Microbial

Substances

  • Anti-Bacterial Agents