Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection
Open accessAbstract
Staphylococcus aureus is a frequent cause for serious, chronic and therapy-refractive infections in spite of susceptibility to antibiotics in vitro. In chronic infections, altered bacterial phenotypes, such as small colony variants (SCVs), have been found. Yet, it is largely unclear whether the ability to interconvert from the wild-type to the SCV phenotype is only a rare clinical and/or just laboratory phenomenon or is essential to sustain an infection. Here, we performed different long-term in vitro and in vivo infection models with S. aureus and we show that viable bacteria can persist within host cells and/or tissues for several weeks. Persistence induced bacterial phenotypic diversity, including SCV phenotypes, accompanied by changes in virulence factor expression and auxotrophism. However, the recovered SCV phenotypes were highly dynamic and rapidly reverted to the fully virulent wild-type form when leaving the intracellular location and infecting new cells. Our findings demonstrate that bacterial phenotype switching is an integral part of the infection process that enables the bacteria to hide inside host cells, which can be a reservoir for chronic and therapy-refractive 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 [5]
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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).”
Background
- Authors
- Tuchscherr, L., Medina, E., Hussain, M., Völker, W., Heitmann, V., Niemann, S., Holzinger, D., Roth, J., Proctor, R. A., Becker, K., Peters, G., & Löffler, B.
- Affiliations
- University Hospital Münster (DE)
- Helmholtz Centre for Infection Research (DE)
- University of Wisconsin–Madison (US)
- Corresponding author
- Löffler, Bettina
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2011-01-26
- Volume
- 3
- Issue
- 3
- Pages
- 129-141
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC3395110
- OpenAlex
- W2124908338
- Cited by
- 437
- References
- 57
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 34 · 2023: 32 · 2022: 23 · 2021: 31 · 2020: 34 · 2019: 40 · 2018: 28 · 2017: 26 · 2016: 28 · 2015: 32 · 2014: 31 · 2013: 28 · 2012: 21
- FWCI
- 19.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HZI (Helmholtz Centre for Infection Research) (submittedVersion)
- Funders
- Transregional Collaborative Research Centre 34
- Interdisciplinary Center for Clinical Research
- Bundesministerium für Bildung und Forschung (01KI0700, 0315830B)
- SFB 492/B9 ‘Extracellular Matrix’
- Deutsche Forschungsgemeinschaft (HA 3177/2‐1)
- 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, phenotypic switching, small colony variants, chronic infection, intracellular persistence, host immune evasion, virulence factor expression, antibiotic resistance
- MeSH terms
- Animals, Cell Line, Chronic Disease, Disease Models, Animal, Energy Metabolism, Female, Humans, Mice, Inbred C57BL, Phagocytes, Staphylococcal Infections, Staphylococcus aureus, Gene Expression Profiling, Virulence Factors, Microbial Viability, Mice, Metabolic Networks and Pathways, Immune Evasion
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