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Jeff Errington, "L-form bacteria: from the origins of life to recurrent infection"
Centre for Bacterial Cell Biology
Abstract: The peptidoglycan cell wall is a defining structure of the bacteria. It is the target for our best antibiotics and fragments of the wall trigger powerful innate immune responses against infection. The genes for peptidoglycan synthesis are present in most bacterial lineages, suggesting that the wall emerged early in cellular evolution. Surprisingly, many bacteria can switch, sometimesspontaneously,into a cell wall deficient “L-form” state in which they become completely resistant to many cell wall active antibiotics. Remarkably, L-form growth is completely independent of the complex FtsZ-based division machine that is essential in almost all bacteria. Proliferation occurs, instead, by a seemingly haphazard process involving membrane blebbing or tubulation and scission, leading to progeny of irregular size and shape. The switch to this mode of proliferation seems to require only the upregulation of membrane synthesis, leading to an increased surface area to volume ratio. Microfluidic methods have recently provided a useful method with which to probe more deeply into the requirements for L-form division. L-forms may provide insights into how primitive cells proliferated before the evolution of the cell wall. Recent results have highlighted remarkable antagonistic interactions between lysozyme and β-lactams with important potential implications for antibiotic evasion and recurrent infection. Finally, we detected L-form like cells in the urine of most patients participating in a recent longitudinal study of elderly patients with recurrent UTI, and show that the isolated bacteria can readily switch in and out of the L-form state.