Understanding Beta-Lactam-Induced Lysis at the Single-Cell Level

Mechanical rupture, or lysis, of the cytoplasmic membrane is a common cell death pathway in bacteria occurring in response to beta-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 beta-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 beta-lactams aimed at targeting cellular turgor.

Automated summary

By experimentally analyzing the dynamics of lysis in hundreds of single Escherichia coli cells, it was found that turgor pressure is the only factor that robustly modulates lysis, while mechanosensitive channels do not modulate lysis due to insufficiently fast solute outflow, and cell shape changes result in more severe cellular lesions but do not influence the dynamics of lysis. These results provide insights into a single-cell view of bacterial cell lysis and highlight approaches of combatting antibiotic tolerance to beta-lactams by targeting cellular turgor.