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Dewachter L, Bollen C, Wilmaerts D, et al. The Dynamic Transition of Persistence toward the Viable but Nonculturable State during Stationary Phase Is Driven by Protein Aggregation. mBio. 2021;12(4):e0070321doi: 10.1128/mBio.00703-21.
Dewachter, L., Bollen, C., Wilmaerts, D., Louwagie, E., Herpels, P., Matthay, P., Khodaparast, L., Khodaparast, L., Rousseau, F., Schymkowitz, J., & Michiels, J. (2021). The Dynamic Transition of Persistence toward the Viable but Nonculturable State during Stationary Phase Is Driven by Protein Aggregation. mBio, 12(4), e0070321. https://doi.org/10.1128/mBio.00703-21
Dewachter, Liselot, et al. "The Dynamic Transition of Persistence toward the Viable but Nonculturable State during Stationary Phase Is Driven by Protein Aggregation." mBio vol. 12,4 (2021): e0070321. doi: https://doi.org/10.1128/mBio.00703-21
Dewachter L, Bollen C, Wilmaerts D, Louwagie E, Herpels P, Matthay P, Khodaparast L, Khodaparast L, Rousseau F, Schymkowitz J, Michiels J. The Dynamic Transition of Persistence toward the Viable but Nonculturable State during Stationary Phase Is Driven by Protein Aggregation. mBio. 2021 Aug 31;12(4):e0070321. doi: 10.1128/mBio.00703-21. Epub 2021 Aug 03. PMID: 34340538; PMCID: PMC8406143.
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mBio. 2021 Aug 31;12(4):e0070321. doi: 10.1128/mBio.00703-21. Epub 2021 Aug 03.

The Dynamic Transition of Persistence toward the Viable but Nonculturable State during Stationary Phase Is Driven by Protein Aggregation.

mBio

Liselot Dewachter, Celien Bollen, Dorien Wilmaerts, Elen Louwagie, Pauline Herpels, Paul Matthay, Ladan Khodaparast, Laleh Khodaparast, Frederic Rousseau, Joost Schymkowitz, Jan Michiels

Affiliations

  1. Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.
  2. Center for Microbiology, VIB-KU Leuven, Leuven, Belgium.
  3. Switch Laboratory, Center for Brain and Disease Research, VIB-KU Leuven, Leuven, Belgium.
  4. Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

PMID: 34340538 PMCID: PMC8406143 DOI: 10.1128/mBio.00703-21

Abstract

Decades of research into bacterial persistence has been unable to fully characterize this antibiotic-tolerant phenotype, thereby hampering the development of therapies effective against chronic infections. Although some active persister mechanisms have been identified, the prevailing view is that cells become persistent because they enter a dormant state. We therefore characterized starvation-induced dormancy in Escherichia coli. Our findings indicate that dormancy develops gradually; persistence strongly increases during stationary phase and decreases again as persisters enter the viable but nonculturable (VBNC) state. Importantly, we show that dormancy development is tightly associated with progressive protein aggregation, which occurs concomitantly with ATP depletion during starvation. Persisters contain protein aggregates in an early developmental stage, while VBNC cells carry more mature aggregates. Finally, we show that at least one persister protein, ObgE, works by triggering aggregation, even at endogenous levels, and thereby changing the dynamics of persistence and dormancy development. These findings provide evidence for a genetically controlled, gradual development of persisters and VBNC cells through protein aggregation.

Keywords: ObgE; VBNC; antibiotic resistance; antibiotic tolerance; chronic infection; dormancy; persistence; protein aggregation; stationary phase

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