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Updated: Jun 17, 2026
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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Conserved and context-dependent changes in pathogen and host cell gene expression during Staphylococcus aureus
Elizabeth A Holmes1, Adam Waalkes1, Janessa D Lewis1
1Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
BMC Microbiology
|June 16, 2026
Summary
Staphylococcus aureus intracellular survival depends on specific bacterial and host cell gene expression changes. Most changes varied by bacterial strain and host cell type, revealing context-specific infection dynamics.
Area of Science:
- Microbiology
- Molecular Biology
- Genomics
Background:
- Staphylococcus aureus's opportunistic intracellular lifestyle aids chronic infections.
- Factors enabling bacterial invasion, persistence, and host responses are not fully understood.
- Variability across bacterial strains and host cell types complicates infection dynamics.
Purpose of the Study:
- To investigate S. aureus and host cell transcriptional changes during intracellular invasion.
- To compare these changes across different S. aureus strains and human cell lines.
- To identify conserved and context-specific factors in S. aureus pathogenesis.
Main Methods:
- Dual RNA-sequencing (RNA-seq) of S. aureus and host cells post-invasion.
- Comparison of transcriptional profiles between two S. aureus strains (JE2, ATCC29213) and two human cell lines (THP-1 macrophages, CCL-185 lung epithelial cells) over time (3h and 24h).
- CRISPR interference (CRISPRi) knockdown experiments to assess the phenotypic impact of key bacterial genes.
Main Results:
- Bacterial and host cell transcriptional changes were highly dependent on the specific strain-cell combination.
- Most significant transcriptional alterations occurred early in infection (by 3 hours).
- Conserved bacterial changes included altered metal ion homeostasis and pyrimidine biosynthesis, with downregulated anaerobic respiration and virulence factors.
- Host cell responses differed markedly between cell types and were influenced by the infecting S. aureus strain.
- CRISPRi experiments confirmed the role of significantly altered bacterial genes in host cell invasion (26/32 genes, 81%).
Conclusions:
- A small set of conserved transcriptional changes in S. aureus are crucial for intracellular pathogenesis across various host-pathogen combinations.
- The majority of transcriptional responses are contingent, varying significantly based on the specific bacterial strain, host cell type, or their interaction.
- This highlights the context-dependent nature of S. aureus intracellular infection strategies.
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