L-form bacteria, chronic diseases and the origins of life

Philos Trans R Soc Lond B Biol Sci. 2016 Nov 5;371(1707):20150494. doi: 10.1098/rstb.2015.0494.


The peptidoglycan cell wall is widely conserved across the bacterial domain, suggesting that it appeared early in the evolution of bacteria. It is normally essential but under certain conditions wall-deficient or 'L-form' bacteria can be isolated. In Bacillus subtilis this normally requires two genetic changes. The first, exemplified by mutations shutting down wall precursor synthesis, works by increasing membrane synthesis. This promotes the unusual form of proliferation used by L-forms, involving a range of relatively disorganized membrane blebbing or vesiculation events. The secondary class of mutations probably work by relieving oxidative stress that L-forms may incur due to their unbalanced metabolism. Repression or inhibition of cell wall precursor synthesis can stimulate the L-form transition in a wide range of bacteria, of both Gram-positive and -negative lineages. L-forms are completely resistant to most antibiotics working specifically on cell wall synthesis, such as penicillins and cephalosporins, consistent with the many reports of their involvement in various chronic diseases. They are potentially important in biotechnology, because lack of a wall can be advantageous in a range of production or strain improvement applications. Finally, L-forms provide an interesting model system for studying early steps in the evolution of cellular life.This article is part of the themed issue 'The new bacteriology'.

Keywords: Bacillus subtilis; L-forms; bacterial cell wall; biotechnology; infectious disease; origins of life.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Bacillus subtilis / genetics
  • Bacillus subtilis / physiology*
  • Cell Wall / metabolism*
  • Chronic Disease*
  • L Forms / genetics
  • L Forms / physiology*
  • Mutation
  • Peptidoglycan / metabolism


  • Anti-Bacterial Agents
  • Peptidoglycan