Impact of either elevated or decreased levels of cytochrome bd expression on Shigella flexneri virulence
Related Experiment Video
Updated: Oct 25, 2026
Epithelial Cell Infection Analyses with Shigella
Published on: February 9, 2024
S S Way1, S Sallustio, R S Magliozzo
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461-1602, USA.
Abstract:
Shigella spp. are the major cause of bacillary dysentery worldwide. The pathogenic process involves bacterial invasion and lysis of the phagocytic vacuole, followed by replication and movement within the cell cytoplasm and, ultimately, spread directly into adjacent cells. This study demonstrates that S. flexneri cytochrome bd expression is necessary for normal intracellular survival and virulence. Cytochrome bd is one of two terminal oxidases in the bacterial respiratory chain that reduce molecular oxygen to water, utilizing intermediates shuttled through the electron transport chain. S. flexneri mutants that contain a disruption in the cydC locus, which leads to defective cytochrome bd expression, or in the riboflavin (ribE) or ubiquinol-8 (ubiH) biosynthetic pathway, which leads to elevated cytochrome bd expression, were evaluated in intracellular survival and virulence assays. The cydC mutant formed significantly smaller plaques, had significantly decreased intracellular survival, and had a 100-fold increase in lethal dose for mice compared with the wild type. The ribE and ubiH mutants each formed significantly larger plaques and had a 10-fold decrease in lethal dose for mice compared with the wild type. The data indicate that expression of cytochrome bd is required for S. flexneri intracellular survival and virulence.
Insights
Shigella flexneri requires cytochrome bd for intracellular survival and virulence. Disrupting its expression impairs bacterial virulence, while altered expression affects disease severity in mice.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Shigella spp. cause bacillary dysentery globally.
- Pathogenesis involves invasion, intracellular replication, and cell-to-cell spread.
- Cytochrome bd is a key terminal oxidase in the bacterial respiratory chain.
Purpose of the Study:
- To investigate the role of S. flexneri cytochrome bd expression in intracellular survival and virulence.
- To evaluate the impact of altered cytochrome bd expression on bacterial pathogenesis.
Main Methods:
- Construction and analysis of S. flexneri mutants with disrupted cydC or altered ribE/ubiH expression.
- Intracellular survival assays to assess bacterial persistence within host cells.
- Virulence assays in a mouse model to determine lethal dose and plaque formation.
Main Results:
- A cydC mutant with defective cytochrome bd expression showed reduced intracellular survival and a 100-fold increase in lethal dose.
- Mutants with elevated cytochrome bd expression (ribE or ubiH) exhibited increased plaque formation and a 10-fold decrease in lethal dose.
- Cytochrome bd expression levels directly correlate with S. flexneri virulence.
Conclusions:
- Cytochrome bd expression is essential for Shigella flexneri intracellular survival.
- Modulating cytochrome bd levels significantly impacts bacterial virulence and disease outcomes.
- Targeting cytochrome bd may offer a strategy to combat Shigella infections.
Related Concept Videos
01:28Regulation of Bacterial Virulence
01:20Determinants of Bacterial Pathogenicity and Virulence