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Updated: Jun 26, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Temporal tuning of switch-like virulence expression resolves environmental uncertainty through phenotypic
1Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA; Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
Salmonella Typhimurium tunes virulence gene expression probabilistically. This allows bacteria to adapt to uncertain host environments, ensuring survival and replication within host cells.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Gene Regulation
Background:
- Gene regulatory networks adapt to environmental uncertainty.
- Intracellular bacterial pathogens face dynamic and heterogeneous host environments.
- Virulence gene regulation is crucial for bacterial survival and replication.
Purpose of the Study:
- Investigate Salmonella Typhimurium's SPI-2 gene regulation.
- Determine if SPI-2 expression is tuned to intracellular-like environments.
- Evaluate the role of SsrA and SsrB in SPI-2 regulation.
Main Methods:
- Live-cell reporters
- Single-molecule fluorescence in situ hybridization (smFISH)
- In vitro and in vivo infection models (macrophages)
Main Results:
- SPI-2 expression is bimodal in clonal populations.
- Single-cell SPI-2 activation occurs progressively and is modulated by signal strength.
- SsrA and SsrB levels control SPI-2 heterogeneity, with SsrA gating activation.
- Heterogeneous SPI-2 activation occurs during macrophage infection and is affected by phagosome acidification.
Conclusions:
- Salmonella Typhimurium probabilistically tunes SPI-2 expression to intracellular environments.
- This strategy resolves uncertainty in ambiguous host conditions.
- Bimodal gene expression allows adaptation to dynamic intracellular environments.
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