Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Enteric yersiniae infections can lead to persistent enteritis and autoimmune disorders.
• Bacterial survival during intestinal transmigration and colonization relies on overcoming host immune responses.
• Mechanisms by which yersiniae establish persistent infections are not fully understood.

Purpose of the Study:

• To investigate the role of the CNFY toxin in enteric yersiniae pathogenesis.
• To understand how CNFY influences host immune responses and bacterial persistence.
• To explore strategies for controlling persistent yersiniae infections.

Main Methods:

• Analysis of CNFY toxin function in vitro and in vivo.
• Assessment of host immune responses, including inflammatory markers and interferon-gamma.
• Microbiota analysis and bacterial transcriptional profiling.

Main Results:

• The CNFY toxin induces inflammatory responses, leading to tissue destruction and bacterial clearance.
• Suppression of CNFY enhances interferon-gamma-mediated antimicrobial activities and tolerogenesis.
• Reduced CNFY function triggers early bacterial transcriptional reprogramming towards persistence.

Conclusions:

• CNFY toxin plays a dual role in yersiniae infections, initially promoting inflammation but its suppression facilitates persistence.
• Interferon-gamma mediated responses are crucial for controlling yersiniae, and CNFY suppression redirects bacterial strategy towards a commensal lifestyle.
• Targeting CNFY function could offer new therapeutic avenues for managing persistent enteric yersiniae infections.