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Molecular biology of cell wall regeneration in L-form bacteria

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Understanding cell wall regeneration in bacteria

Bacteria lacking the cell wall structure, also known as L-form bacteria, are believed to play an instrumental role in relapsing or chronic infections. European scientists wished to understand how these bacteria regain their ability to synthesise a cell wall and how this regeneration is linked to an infectious state.

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The bacteria cell wall is the outermost layer encountered in some bacteria, algae and fungi, but is absent from animal cells. The absence of the cell wall renders L-form cells highly abnormal in size and shape, sensitive to osmotic shock but highly resistant to antibiotics that work on the cell wall. L-form cells at some stage revert to the walled state and disease resumes in patients with persistent or recurrent infections. It is, therefore, hypothesised that blocking regeneration may be a way of tackling these infections. However, our knowledge on the mechanisms that are implicated in this reversion is limited. The EU-funded 'Molecular biology of cell wall regeneration in L-form bacteria' (REGENERATE) project aimed to provide insight into the biology of L-form bacteria by focusing on their ability to revert to their cell walled state. Given the difficulty in generating and propagating L-forms, scientists used advanced genetic methods and mutant strains previously developed in the host lab. These tools enabled them to reproducibly obtain L-forms from laboratory strains of Bacillus subtilis. Proteoglycan (PG), the main constituent of the cell wall, is believed to require a primer for its synthesis and thus bacteria completely devoid of PG propagated for a period of time would be unable to regain their original shape. To test this hypothesis, REGENERATE scientists shut down PG synthesis in L-bacteria and propagated them for many generations. Then, by turning these genes on again, they observed that L-form cells could resume PG synthesis and revert to the cell walled state, thus disproving the priming theory. A better understanding of the cell wall regeneration process should provide important insight into the possible role of L-forms as causative agents of chronic infections. Through a delineation of the mechanisms implicated in the transition of L-bacteria to the walled state it will be possible to design novel anti-bacterial therapies to tackle such infections.

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