The fate of multidrug tolerant bacteria: from single cells to microbial communities. (360G-Wellcome-204684_Z_16_Z)

Many bacterial infections cannot be cured, even when caused by a pathogen that is not resistant to antibiotics. Central to this effect is the presence of a subpopulation of phenotypic variants called persisters, which enter a dormant state and can survive exposure to a broad range of antibiotics, causing recurrent and chronic infections. Persistence can be triggered by a variety of mechanisms, but it is unknown if these different mechanisms lead to the same cell state, and the same tolerance to antibiotics. Because persister cells are rare they are difficult to study with bulk assays. I will use microfluidics and quantitative fluorescence microscopy of Escherichia coli cells to investigate how persistence states differ from one another in their gene expression and their tolerance to antibiotics. I will study how these cells revive from their dormant state, and at what point they become susceptible again. Chronic infections are often associated with biofilm formation, and increased antibiotic tolerance. By imaging persisters within bacterial colonies, I will establish if biofilms directly afford protection against antibiotic treatment, or rather if biofilms simply prevent removal of existing persister cells, allowing them to repopulate after antibiotic treatment finishes.