Intracellular Staphylococcus aureus persisters upon antibiotic exposure
Open accessAbstract
Bacterial persister cells are phenotypic variants that exhibit a transient non-growing state and antibiotic tolerance. Here, we provide in vitro evidence of Staphylococcus aureus persisters within infected host cells. We show that the bacteria surviving antibiotic treatment within host cells are persisters, displaying biphasic killing and reaching a uniformly non-responsive, non-dividing state when followed at the single-cell level. This phenotype is stable but reversible upon antibiotic removal. Intracellular S. aureus persisters remain metabolically active but display an altered transcriptomic profile consistent with activation of stress responses, including the stringent response as well as cell wall stress, SOS and heat shock responses. These changes are associated with multidrug tolerance after exposure to a single antibiotic. We hypothesize that intracellular S. aureus persisters may constitute a reservoir for relapsing infection and could contribute to therapeutic failures.
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Fungal persisters are often recalcitrant to multiple antibiotics, as has been observed in antibiotic persistence.
“In antibiotic persistence, persisters are often recalcitrant to multiple antibiotics [49,50], which has been observed with fungal persisters as well.”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [49]
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- Authors
- Peyrusson, F., Varet, H., Nguyen, T. K., Legendre, R., Sismeiro, O., Coppée, J.-Y., Wolz, C., Tenson, T., & Van Bambeke, F.
- Affiliations
- UCLouvain (BE)
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur (FR)
- University of Tübingen (DE)
- University of Tartu (EE)
- ORCID
- Venue
- Nature Communications
- Published
- 2020-05-04
- Volume
- 11
- Issue
- 1
- Pages
- 2200-2200
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7198484
- OpenAlex
- W3023088732
- Cited by
- 392
- References
- 76
- Citations by year
- 2026: 68 · 2025: 79 · 2024: 73 · 2023: 61 · 2022: 50 · 2021: 40 · 2020: 21
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace repository (University of Tartu) (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR10‐NBS‐09‐08)
- Deutsche Forschungsgemeinschaft (SFB156)
- Eesti Teadusagentuur (PRG335)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Staphylococcus aureus, persister cells, intracellular persistence, antibiotic tolerance, stringent response, cell wall stress response, SOS response, heat shock response, multidrug tolerance, infection relapse, host cell infection, single-cell tracking
- MeSH terms
- A549 Cells, THP-1 Cells, Animals, Anti-Bacterial Agents, Cell Line, Cells, Cultured, Energy Metabolism, Humans, Macrophages, Microbial Sensitivity Tests, Staphylococcus aureus, Gene Expression Regulation, Bacterial, Microscopy, Confocal, Gene Expression Profiling, Drug Resistance, Multiple, Bacterial, Cell Line, Tumor, Microbial Viability, Mice, MCF-7 Cells
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