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Lysozyme Counteracts β-Lactam Antibiotics by Promoting the Emergence of L-Form Bacteria

Lookup NU author(s): Dr Yoshikazu Kawai, Dr Katarzyna Mickiewicz, Professor Jeff ErringtonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 The Authors β-lactam antibiotics inhibit bacterial cell wall assembly and, under classical microbiological culture conditions that are generally hypotonic, induce explosive cell death. Here, we show that under more physiological, osmoprotective conditions, for various Gram-positive bacteria, lysis is delayed or abolished, apparently because inhibition of class A penicillin-binding protein leads to a block in autolytic activity. Although these cells still then die by other mechanisms, exogenous lytic enzymes, such as lysozyme, can rescue viability by enabling the escape of cell wall-deficient “L-form” bacteria. This protective L-form conversion was also observed in macrophages and in an animal model, presumably due to the production of host lytic activities, including lysozyme. Our results demonstrate the potential for L-form switching in the host environment and highlight the unexpected effects of innate immune effectors, such as lysozyme, on antibiotic activity. Unlike previously described dormant persisters, L-forms can continue to proliferate in the presence of antibiotic. Innate immune effectors with lytic activity can paradoxically promote a switch to an antibiotic resistant form that allows bacteria to proliferate in host environments.

Publication metadata

Author(s): Kawai Y, Mickiewicz K, Errington J

Publication type: Article

Publication status: Published

Journal: Cell

Year: 2018

Volume: 172

Issue: 5

Pages: 1038-1049.e10

Print publication date: 22/02/2018

Online publication date: 15/02/2018

Acceptance date: 02/04/2016

Date deposited: 05/03/2018

ISSN (print): 0092-8674

ISSN (electronic): 1097-4172

Publisher: Cell Press


DOI: 10.1016/j.cell.2018.01.021


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