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Cell. 2018 Feb 22;172(5):1038-1049.e10. doi: 10.1016/j.cell.2018.01.021. Epub 2018 Feb 15.

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

Author information

1
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK.
2
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK. Electronic address: jeff.errington@ncl.ac.uk.

Abstract

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.

KEYWORDS:

Bacillus subtilis; Staphylococcus aureus; antibiotic action; antibiotic resistance; bacterial cell biology; bacterial cell wall; bacterial genetics; lysozyme; macrophage; penicillin

PMID:
29456081
PMCID:
PMC5847170
DOI:
10.1016/j.cell.2018.01.021
[Indexed for MEDLINE]
Free PMC Article

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