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Shigella Serotypes Associated With Carriage in Humans Establish Persistent Infection in Zebrafish
Vincenzo Torraca1,2,3, Dominik Brokatzky1, Sydney L Miles1
1Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Abstract:
Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the men who have sex with men (MSM) community are attributed to 3 serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic tolerant. Establishment of persistent infection depends on the O-antigen, a key constituent of the bacterial surface and a serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to persist. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans.
Insights
Shigella bacteria can establish persistent infections in zebrafish, evading the immune system and becoming antibiotic tolerant. This persistence is linked to the O-antigen, crucial for Shigella serotypes common in men who have sex with men (MSM) infections.
Area of Science:
- Microbiology and Immunology
- Infectious Diseases
- Zebrafish Models in Research
Background:
- Shigella, a group of enteroinvasive Escherichia coli, comprises over 40 serotypes.
- Most infections in men who have sex with men (MSM) are linked to Shigella sonnei, Shigella flexneri 2a, and 3a.
Purpose of the Study:
- To investigate Shigella's ability to establish persistent infections in vivo.
- To identify bacterial factors contributing to persistent Shigella infections.
- To evaluate the zebrafish model for studying Shigella pathogenesis.
Main Methods:
- Utilizing the zebrafish model to study Shigella infection dynamics.
- Assessing bacterial clearance, antibiotic tolerance, and immune response (macrophage death).
- Analyzing the role of the O-antigen in persistent infection establishment.
Main Results:
- Shigella establishes persistent, antibiotic-tolerant infections in zebrafish, evading immune clearance.
- O-antigen, a serotype determinant, is essential for establishing persistent infection.
- Shigella isolates linked to MSM transmission persisted in zebrafish, unlike other serotypes.
- Persistent Shigella serotypes induced less macrophage death compared to non-persisting ones.
Conclusions:
- The zebrafish model effectively illuminates factors underlying persistent Shigella infections.
- The O-antigen plays a critical role in Shigella persistence and serotype-specific pathogenesis.
- Understanding these mechanisms can inform strategies against Shigella infections, particularly in vulnerable populations.
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