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Journal article
Understanding Beta-Lactam-Induced Lysis at the Single-Cell Level
Frontiers in microbiology, Vol.12, 712007
27/Jul/2021
PMID: 34421870
Abstract
Mechanical rupture, or lysis, of the cytoplasmic membrane is a common cell death pathway in bacteria occurring in response to β-lactam antibiotics. A better understanding of the cellular design principles governing the susceptibility and response of individual cells to lysis could indicate methods of potentiating β-lactam antibiotics and clarify relevant aspects of cellular physiology. Here, we take a single-cell approach to bacterial cell lysis to examine three cellular features—turgor pressure, mechanosensitive channels, and cell shape changes—that are expected to modulate lysis. We develop a mechanical model of bacterial cell lysis and experimentally analyze the dynamics of lysis in hundreds of single Escherichia coli cells. We find that turgor pressure is the only factor, of these three cellular features, which robustly modulates lysis. We show that mechanosensitive channels do not modulate lysis due to insufficiently fast solute outflow, and that cell shape changes result in more severe cellular lesions but do not influence the dynamics of lysis. These results inform a single-cell view of bacterial cell lysis and underscore approaches of combatting antibiotic tolerance to β-lactams aimed at targeting cellular turgor.
Details
- Title
- Understanding Beta-Lactam-Induced Lysis at the Single-Cell Level
- Creators
- Felix Wong (Corresponding Author) - Massachusetts Institute of TechnologySean Wilson - Harvard UniversityRalf Helbig - Leibniz Institute of Polymer ResearchSmitha Hegde - University of EdinburghOlha Aftenieva - Leibniz Institute of Polymer ResearchHai Zheng - , , , , , , , , , , , , , , , ,Chenli Liu - Shenzhen Institutes of Advanced TechnologyTeuta Pilizota - University of EdinburghEthan C. Garner - Harvard UniversityAriel Amir (Corresponding Author) - Harvard UniversityLars D. Renner (Corresponding Author) - Leibniz Institute of Polymer Research
- Resource Type
- Journal article
- Publication Details
- Frontiers in microbiology, Vol.12, 712007; 27/Jul/2021
- Number of pages
- 18
- Publisher
- Frontiers Media S.A
- Language
- English
- DOI
- https://doi.org/10.3389/fmicb.2021.712007
- PMID
- 34421870
- Grant note
- We thank Sue Sim, Anastasiya Yakhnina, Thomas G. Bernhardt, Douglas B. Weibel, and members of the Weibel lab for providing the assorted E. coli strains summarized in Supplementary Table 1, Georgia Squyres and Yingjie Sun for microscopy assistance, Sven van Teeffelen, Gizem Özbaykal, and Namiko Mitarai for discussions, and the Harvard Department of Statistics Consulting Service for helpful feedback. Funding - FW was supported by the James S. McDonnell Foundation and a National Science Foundation (NSF) Graduate Research Fellowship under Grant No. DGE1144152. SH was supported by the Darwin Trust. SH and TP were supported by the Industrial Biotechnology Innovation Centre (IBioIC) and the Biotechnology and Biological Sciences Research Council UK via the Crossing Biological Membrane Network in Industrial Biotechnology and Bioenergy (CBMNet). EG was supported by the National Institutes of Health under Grant No. DP2AI117923-01, a Smith Family Award, and a Searle Scholar Fellowship. AA was supported by an NSF CAREER Award under Grant No. 1752024. FW and AA were supported by the Kavli Institute for Bionano Science and Technology at Harvard and the Materials Research and Engineering Center at Harvard under Grant No. DMR-1420570. EG, AA, and LR were supported by the Volkswagen Foundation. Author contributions - FW, AA, and LR conceived the project. FW, SW, CL, TP, EG, AA, and LR designed the research. FW, SW, RH, SH, OA, HZ, and LR performed the research. All authors analyzed the data. FW, SW, TP, EG, AA, and LR wrote the paper with the assistance of all authors.
- Record Identifier
- 993407284503596
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