Antibiotic Resistance via Bacterial Cell Shape-Shifting.

Antibiotic Resistance via Bacterial Cell Shape-Shifting.
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DOI:
10.1128/mbio.00659-22
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发表时间:
2022-06-28
期刊:
影响因子:
6.4
通讯作者:
Banerjee, Shiladitya
Banerjee, Shiladitya
中科院分区:
生物学1区
文献类型:
--
作者:
Ojkic, Nikola;Serbanescu, Diana;Banerjee, Shiladitya

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细菌已经进化为通过有效地降低细胞内抗生素浓度或抗生素结合亲和力来开发抗生素抗性的多种策略,但是细胞形态在抗生素抗性中的作用仍然知之甚少。通过分析抗生素胁迫下不同细菌物种的细胞形态数据,我们发现细菌根据抗生素靶标增加或减少细胞表面积与体积比。使用定量建模,我们表明,通过降低表面积与体积比,细菌可以有效地降低细胞内抗生素浓度,通过减少抗生素流入。该模型进一步预测,细菌可以增加表面积与体积比,以诱导膜靶向抗生素的稀释,与实验数据一致。使用抗生素调节细胞形状和生长的全细胞模型,我们预测细菌可以利用抗生素来增加其适应性的形状转变。最后,我们讨论了抗生素耐药性的其他途径,可能与形状诱导的耐药性协同作用。
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.
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