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Staphylococcus aureus Evades Lysozyme-Based Peptidoglycan Digestion that Links Phagocytosis, Inflammasome Activation, and IL-1β Secretion
Open accessAbstract
IL-1beta produced by phagocytes is important for protection against the mucosal pathogen Staphylococcus aureus. Processing and maturation of this cytokine requires activation of the multiprotein inflammasome complex. We observed that the bacterial cell wall component peptidoglycan (PGN) must be particulate and internalized via phagocytosis to activate NLRP3 inflammasomes and IL-1beta secretion. In the context of S. aureus infection of macrophages, we find that phagocytosis and lysozyme-based bacterial cell wall degradation are necessary to induce IL-1beta secretion. Further, an S. aureus enzyme, PGN O-acetyltransferase A, previously demonstrated to make cell wall PGN resistant to lysozyme, strongly suppresses inflammasome activation and inflammation in vitro and in vivo. These observations demonstrate that phagocytosis and lysozyme-based cell wall degradation of S. aureus are functionally coupled to inflammasome activation and IL-1beta secretion and illustrate a case whereby a bacterium specifically subverts IL-1beta secretion through chemical modification of its cell wall PGN.
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“In contrast to macrophages, which require the internalization of particulate peptidoglycan to activate inflammasome signaling [17], keratinocytes constitutively express IL-1β and thus are primed for activation by surface contact with staphylococci.”
From Staphylococcus aureus activation of caspase 1/calpain signaling mediates invasion through human keratinocytes (2012) · cites this paper as [17]
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Metadata
- Authors
- Shimada, T., Park, B. G., Wolf, A. J., Brikos, C., Goodridge, H. S., Becker, C. A., Reyes, C. N., Miao, E. A., Aderem, A., Götz, F., Liu, G. Y., & Underhill, D. M.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Institute for Systems Biology (US)
- University of Tübingen (DE)
- Corresponding author
- Underhill, David M.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 7
- Issue
- 1
- Pages
- 38-49
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC2818986
- OpenAlex
- W2064358027
- Cited by
- 274
- References
- 65
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 13 · 2023: 12 · 2022: 17 · 2021: 17 · 2020: 11 · 2019: 18 · 2018: 21 · 2017: 13 · 2016: 20 · 2015: 20 · 2014: 13 · 2013: 17 · 2012: 26
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Genentech
- National Institute of General Medical Sciences (GM-085796, R01GM085796)
- National Institute of Allergy and Infectious Diseases (R01AI025032)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Infectious Diseases › Streptococcal Infections and Treatments
- Keywords
- Staphylococcus aureus, peptidoglycan, lysozyme, phagocytosis, NLRP3 inflammasome, IL-1β secretion, macrophages, inflammation, bacterial evasion of host defense
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Bacterial Proteins, Carrier Proteins, Macrophages, Models, Biological, Muramidase, Peptidoglycan, Phagosomes, Staphylococcus aureus, Interleukin-1beta
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