Year: 2021
Type: article
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.
Source: Frontiers in Microbiology
Institutions: Broad Institute, Harvard University, Massachusetts Institute of Technology, Center for Systems Biology, Max Bergmann Center of Biomaterials, Leibniz Institute of Polymer Research, Wellcome Centre for Cell Biology, University of Edinburgh, Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: National Science Foundation, James S. McDonnell Foundation, Volkswagen Foundation, Industrial Biotechnology Innovation Centre, Darwin Trust of Edinburgh, National Institutes of Health, Directorate for Biological Sciences, National Institute of Allergy and Infectious Diseases, Division of Materials Research
Awards: G1020486556, G226688381, G2818530089, G3366412161, G3527015187, CAREER: Stochastic Effects in the Microbial Cell Cycle: From Single-cell Level Variability to Population Growth, Dissecting bacterial cell wall synthesis using in vivo single molecule tracking, G5193373007, G6671297155, G6711204355, Graduate Research Fellowship Program (GRFP), Materials Research Science and Engineering Center, G8954024240
OpenAlex ID: W3184479113