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Updated: Jun 16, 2026

Quantifying Yersinia pseudotuberculosis Type III Secretion System Activity Following Iron Starvation and Anaerobic Growth
Published on: May 31, 2024
The yersiniabactin transport system is critical for the pathogenesis of bubonic and pneumonic plague
Jacqueline D Fetherston1, Olga Kirillina, Alexander G Bobrov
1Department of Microbiology, Immunology, and Molecular Genetics, MS415 Medical Center, University of Kentucky, Lexington, KY 40536-0298, USA.
Abstract:
Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an approximately 24-fold-higher 50% lethal dose (LD(50)) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.
Insights
The Yersinia pestis yersiniabactin (Ybt) system is crucial for iron acquisition and virulence in plague models. While essential for bubonic plague, its role in pneumonic plague differs between Ybt synthesis and transport.
Area of Science:
- Microbiology
- Pathogenesis
- Bacterial Iron Acquisition
Background:
- Iron acquisition is vital for bacterial pathogens like Yersinia pestis.
- The yersiniabactin (Ybt) siderophore system is a primary iron uptake mechanism for Y. pestis.
- Ybt facilitates iron acquisition from host proteins like transferrin and lactoferrin.
Purpose of the Study:
- To investigate the role of the Ybt system in Yersinia pestis virulence.
- To compare the importance of Ybt siderophore synthesis versus transport in different plague models.
- To identify other virulence factors involved in pneumonic plague pathogenesis.
Main Methods:
- Construction and testing of Y. pestis mutants deficient in Ybt transport or synthesis.
- Evaluation of mutant virulence in mouse models of bubonic (subcutaneous injection) and pneumonic (intranasal instillation) plague.
- Assessment of bacterial growth under iron-restricted conditions in vitro.
- Comparison of virulence loss between Ybt mutants and a pgm deletion mutant.
Main Results:
- Ybt system mutants were avirulent in the bubonic plague model.
- In the pneumonic plague model, Ybt biosynthetic mutants showed significantly reduced virulence (24-fold higher LD50) compared to transport mutants.
- In vitro, Ybt transport mutants exhibited a more severe growth defect under iron limitation than biosynthetic mutants.
- A deletion mutant of the pgm locus showed a greater loss of virulence than the Ybt biosynthetic mutant.
Conclusions:
- The Ybt system is essential for Y. pestis virulence in bubonic plague.
- Differential roles of Ybt synthesis and transport are evident in pneumonic plague.
- The pgm locus encodes a significant virulence factor for pneumonic plague, independent of Ybt.
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