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

Abstract

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.

Figure 1.

Schematic of the key steps in the walled to L-form transition. Walled cells of rod-shaped bacteria (left) typically grow by elongation of the cell cylinder, governed by the MreB cytoskeletal system, followed by FtsZ-dependent division at mid cell. Lysozyme treatment (for example) (second from left) removes the cell wall, leading to formation of protoplasts, but these are unable to grow due to oxidative damage. Mutations that, in the case of aerobically growing B. subtilis, fall into two classes, enable L-form growth (third from left). The right hand panels show phase contrast images of B. subtilis in the walled (upper) and L-form (lower) states. Text at bottom of figure lists some of the mutational lesions characteristic of classes 1 and 2.