General principles for the formation and proliferation of a wall-free (L-form) state in bacteria
- Newcastle University, United Kingdom
Abstract
The peptidoglycan cell wall is a defining structural feature of the bacterial-kingdom. Curiously, some bacteria have the ability to switch to a wall-free or 'L-form' state. Although known for decades, the general properties of L-forms are poorly understood, largely due to the lack of their systematic analysis in the molecular biology era. Here we show that inhibition of the peptidoglycan precursor synthesis promotes the generation of L-forms from both Gram-positive and Gram-negative bacteria. We show that L-forms generated have in common a mechanism of proliferation involving membrane blebbing and tubulation, which is dependant on an altered rate of membrane synthesis. Crucially, this mode of proliferation is independent of the essential FtsZ-based division machinery. Our results suggest that the L-form mode of proliferation is conserved across the bacterial-kingdom, reinforcing the idea that it could have been used in primitive cells, and opening up its use in the generation of synthetic cells.
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© 2014, Mercier et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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General principles for the formation and proliferation of a wall-free (L-form) state in bacteria
eLife 3:e04629.
https://doi.org/10.7554/eLife.04629
Further reading
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Some bacteria can survive and thrive despite not having a cell wall.
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- Cell Biology
Niemann–Pick disease type C (NPC) is a devastating lysosomal storage disease characterized by abnormal cholesterol accumulation in lysosomes. Currently, there is no treatment for NPC. Transcription factor EB (TFEB), a member of the microphthalmia transcription factors (MiTF), has emerged as a master regulator of lysosomal function and promoted the clearance of substrates stored in cells. However, it is not known whether TFEB plays a role in cholesterol clearance in NPC disease. Here, we show that transgenic overexpression of TFEB, but not TFE3 (another member of MiTF family) facilitates cholesterol clearance in various NPC1 cell models. Pharmacological activation of TFEB by sulforaphane (SFN), a previously identified natural small-molecule TFEB agonist by us, can dramatically ameliorate cholesterol accumulation in human and mouse NPC1 cell models. In NPC1 cells, SFN induces TFEB nuclear translocation via a ROS-Ca2+-calcineurin-dependent but MTOR-independent pathway and upregulates the expression of TFEB-downstream genes, promoting lysosomal exocytosis and biogenesis. While genetic inhibition of TFEB abolishes the cholesterol clearance and exocytosis effect by SFN. In the NPC1 mouse model, SFN dephosphorylates/activates TFEB in the brain and exhibits potent efficacy of rescuing the loss of Purkinje cells and body weight. Hence, pharmacological upregulating lysosome machinery via targeting TFEB represents a promising approach to treat NPC and related lysosomal storage diseases, and provides the possibility of TFEB agonists, that is, SFN as potential NPC therapeutic candidates.
