Staphylococcus aureus Small‐Colony Variants Are Adapted Phenotypes for Intracellular Persistence
Abstract
BACKGROUND: Staphylococcus aureus is an important human pathogen of endovascular diseases, which can take a chronic course with a high relapse rate despite antimicrobial treatment. Thus far, persistent and antibiotic-refractory infections have been largely associated with a subpopulation of S. aureus, the small-colony variants (SCVs). METHODS: In this work, we used endothelial cells to investigate infection with the highly virulent wild-type isolate (6850), 2 stable isogenic SCV phenotypes (hemB mutant IIb13 and JB1), and the complemented mutant. RESULTS: All strains were highly invasive in endothelial cells but largely differed in host response induction. Microarray analysis showed that wild-type phenotypes up-regulated a large number of endothelial genes (including genes involved in innate immunity), whereas the SCVs did not cause these dramatic changes. The inflammatory response and cytotoxicity were strongest shortly after infection and largely decreased within the following days, which was accompanied by a fast elimination of intracellular wild-type bacteria. By contrast, SCVs survived within endothelial cells at high numbers. CONCLUSION: S. aureus intracellular persistence via the development of an adapted subpopulation of SCVs most likely represents an important strategy of S. aureus to hide within the host cells, which could be a reservoir for chronic infections.
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SCVs are effectively phagocytosed by host cells and do not elicit potent immune responses or damage host cells.
“SCVs are effectively phagocytosed by host cells, and transcriptomic studies have shown that SCVs do not elicit potent immune responses or damage host cells (5, 9).”
From Overlooked <i>Candida glabrata</i> petites are echinocandin tolerant, induce host inflammatory responses, and display poor <i>in vivo</i> fitness (2023) · cites this paper as [9]
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“Upon cessation of antibiotic treatment, however, such SCVs can rapidly revert to the fully virulent wild-type (WT) phenotype, causing relapse and seeding chronic infections (5, 9).”
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- Authors
- Tuchscherr, L., Heitmann, V., Hussain, M., Viemann, D., Roth, J., von Eiff, C., Peters, G., Becker, K., & Löffler, B.
- Affiliations
- University Hospital Münster (DE)
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10
- Volume
- 202
- Issue
- 7
- Pages
- 1031-1040
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2134765452
- Cited by
- 275
- References
- 36
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 17 · 2023: 20 · 2022: 16 · 2021: 23 · 2020: 15 · 2019: 19 · 2018: 16 · 2017: 16 · 2016: 15 · 2015: 23 · 2014: 17 · 2013: 21 · 2012: 13
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Staphylococcus aureus, small colony variants, intracellular persistence, endothelial cells, host response, innate immunity, bacterial invasion, chronic infection, antibiotic-refractory infection, endovascular infection, cytotoxicity, inflammation
- MeSH terms
- Cells, Cultured, Cytoplasm, Humans, Staphylococcus aureus, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Endothelial Cells, Host-Pathogen Interactions
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