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Updated: Jan 10, 2026
Author Spotlight: Advancements in Understanding and Combatting Shigella Infections
Published on: February 9, 2024
The pcnB gene sustains Shigella flexneri virulence
Thibault Frisch1, Petra Geiser1, Margarita Komi2
1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Abstract:
The enteropathogen Shigella flexneri employs a Type Three Secretion System (T3SS) to colonize intestinal epithelial cells. Genes encoding the T3SS are located on a large IncFII virulence plasmid, pINV. T3SS expression comes at the expense of slowed Shigella growth and is therefore strictly controlled by both transcriptional and post-transcriptional mechanisms. Following up on a recent genome-wide screen, we here show that the chromosomal gene pcnB, encoding the poly-A polymerase I (PAP-I), slows Shigella growth at 37°C, while it at the same time promotes early colonization of a human epithelial enteroid model. Proteomic profiling revealed that pcnB drives global increase of the Shigella T3SS virulence program. Accordingly, pcnB upholds pINV replication to a level favourable for Shigella virulence. This is achieved through increased degradation of the antisense RNA CopA, involved in plasmid replication control. The pcnB effect on pINV replication was found to also ensure longer-term intraepithelial expansion of Shigella following human intestinal epithelium invasion. Our findings exemplify how an adequate pINV level, sustained by pcnB, underpins the successful execution of Shigella´s infection cycle.
Insights
The poly-A polymerase I (PAP-I) enzyme, encoded by pcnB, enhances Shigella flexneri virulence by promoting colonization and Type Three Secretion System (T3SS) expression. This occurs by increasing virulence plasmid replication, despite slowing bacterial growth.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Shigella flexneri utilizes a Type Three Secretion System (T3SS) for intestinal colonization.
- T3SS genes reside on the pINV virulence plasmid, and their expression is tightly regulated.
- T3SS expression impacts Shigella growth, necessitating a balance between virulence and replication.
Purpose of the Study:
- Investigate the role of the chromosomal gene pcnB, encoding poly-A polymerase I (PAP-I), in Shigella flexneri pathogenesis.
- Determine how pcnB influences T3SS expression, virulence plasmid replication, and bacterial growth.
- Elucidate the mechanisms by which pcnB contributes to Shigella colonization and infection.
Main Methods:
- Genome-wide screening to identify host factors affecting Shigella.
- Growth curve analysis of Shigella strains at 37°C.
- Proteomic profiling to assess global changes in gene expression.
- Enteroid model colonization assays to evaluate early infection dynamics.
- Analysis of pINV plasmid replication and antisense RNA CopA levels.
Main Results:
- The pcnB gene slows Shigella growth at 37°C but promotes early colonization of human enteroids.
- pcnB significantly upregulates the Shigella T3SS virulence program.
- pcnB sustains pINV plasmid replication by increasing degradation of the antisense RNA CopA.
- pcnB-mediated pINV maintenance supports longer-term intraepithelial expansion post-invasion.
Conclusions:
- pcnB is a key regulator linking bacterial growth, virulence plasmid replication, and T3SS expression in Shigella flexneri.
- Adequate pINV levels, maintained by pcnB, are crucial for successful Shigella infection cycle execution.
- pcnB represents a potential target for therapeutic strategies against Shigella infections.
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