An integrative approach points to membrane composition as a key factor in E. coli persistence

In spite of its medical importance, the genetic mechanisms of bacterial persistence, particularly spontaneous (type II) persistence, remain largely unknown. We use an integrative approach, combining mutant genome analysis, transcriptomics and lipid membrane composition analysis, to elucidate said mechanisms. In particular, we analyzed the genome of the high persistence mutant DS1 (hipQ), to identify candidate mutations responsible for the high persistence phenotype. Contrary to a recent study, we find no mutation in ydcI. We compared the expression of spontaneous persistent and growing cells using RNAseq, and find that the activation of stress response mechanisms is likely less important in spontaneous persistence than recent reports suggest. It also indicated that modifications in the cell membrane could play an important role. This hypothesis was then validated by the analysis of the fatty acid composition of persister cells of both types, which have markedly different saturation from growing cells and between each other. Taken together, our results indicate that changing membrane composition might be a key process in persistence.