Lecturer: PhD Talk by Adi Rotem (Balaban Lab)
Abstract:
Antibiotic persistence, typically attributed to dormant bacteria, is known to be a major cause of treatment failure. However, despite many years of intense research, no clear consensus on its mechanism has emerged. Here we demonstrate that high-survival under antibiotics may originate from two fundamentally different growth-arrest archetypes: either from a regulated growth-arrest, leading to a protected dormant cellular state, or from a dysregulated disrupted growth-arrest. Using modelling and experimental approaches including transcriptomics, microcalorimetry, and microfluidics, we unveil the characteristics and vulnerabilities of each growth-arrest archetype. In particular, disrupted bacteria show a general impairment of membrane homeostasis. This understanding resolves previous conflicting results regarding characteristics of persisters and allows tailoring treatments that target the different growth- arrested bacteria. The fundamental distinction between regulated and disrupted growth-arrests should be broadly relevant for the description of cells under stress.