Department of Physics and Astronomy, Institute for the Physics of Living Systems, University College Londongrid.83440.3b, London, United Kingdom.
School of Biological and Behavioural Sciences, Queen Mary University of London, London, United Kingdom.
mBio. 2022 Jun 28;13(3):e0065922. doi: 10.1128/mbio.00659-22. Epub 2022 May 26.
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.
细菌已经进化出多种策略来对抗生素产生耐药性，这些策略通过有效降低细胞内抗生素浓度或抗生素结合亲和力来实现，但细胞形态在抗生素耐药性中的作用仍知之甚少。通过分析不同细菌在抗生素胁迫下的细胞形态数据，我们发现细菌会根据抗生素的作用靶点来增加或减少细胞表面积与体积之比。利用定量建模，我们表明通过降低表面积与体积之比，细菌可以通过减少抗生素流入来有效降低细胞内抗生素浓度。该模型进一步预测，细菌可以增加表面积与体积之比，从而诱导膜靶向抗生素的稀释，这与实验数据一致。通过使用抗生素调节细胞形状和生长的全细胞模型，我们预测了细菌可以利用的形状转化来增加其在抗生素存在时的适应性。最后，我们讨论了可能与形状诱导耐药性协同作用的其他抗生素耐药途径。
