Pathogenesis and virulence of Rhodococcus equi

Area of Science:

• Microbiology
• Immunology
• Veterinary Medicine

Background:

• Rhodococcus equi is a soil-borne bacterium causing severe pyogranulomatous pneumonia in foals and immunocompromised humans.
• The bacterium resists macrophage defenses, establishing intracellular residence, and can disseminate to other body sites.
• Ulcerative colitis is a common sequela in foals infected with R. equi.

Purpose of the Study:

• To investigate the virulence factors of Rhodococcus equi, focusing on plasmid-encoded proteins.
• To understand the role of VapA and other plasmid-associated factors in R. equi pathogenesis in different hosts.
• To explore mechanisms of R. equi virulence and host immune response in experimental models.

Main Methods:

• Comparative analysis of R. equi strains isolated from horses and humans.
• Assessment of bacterial replication within macrophages.
• Experimental infection models in mice to evaluate bacterial clearance and granuloma formation.
• Investigation of plasmid possession and VapA expression in relation to virulence.

Main Results:

• All R. equi strains from horses with disease possess a large plasmid and express VapA.
• Plasmid-containing R. equi strains replicate within mouse tissues and are associated with granuloma development.
• Most human R. equi isolates express VapA-related proteins with reduced virulence, or beta-lactam resistance in plasmid-negative strains.

Conclusions:

• Plasmid possession and VapA expression are critical virulence determinants in equine R. equi infections.
• Human R. equi infections exhibit diverse virulence mechanisms, with VapA being less common than in horses.
• Host immune status significantly influences the outcome of R. equi infections, with intact cellular immunity necessary for bacterial clearance.