Cell
Volume 172, Issue 5, 22 February 2018, Pages 1038-1049.e10
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Article
Lysozyme Counteracts β-Lactam Antibiotics by Promoting the Emergence of L-Form Bacteria

https://doi.org/10.1016/j.cell.2018.01.021Get rights and content
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Highlights

  • On isotonic media, β-lactams can kill by non-lytic mechanisms

  • Lysozyme protects from β-lactam killing by enabling L-form escape

  • Immune cells can convert bacteria to L-forms, protecting them from β-lactams

  • L-forms could act as persister cells that grow in the presence of β-lactams

Summary

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

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

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