Characteristic Metabolic Changes in Skeletal Muscle Due to Vibrio vulnificus Infection in a Wound Infection Model

Area of Science:

• Microbiology
• Pathogenesis
• Metabolomics

Background:

• Vibrio vulnificus is a marine bacterium causing severe wound infections and septicemia.
• Invasive V. vulnificus infections can lead to necrotizing fasciitis and high mortality.
• Metabolic alterations in host skeletal muscle during V. vulnificus infection remain poorly understood.

Purpose of the Study:

• To elucidate metabolic changes in mouse skeletal muscle infected with V. vulnificus.
• To investigate the role of the multifunctional-autoprocessing repeats-in-toxin (MARTX) in V. vulnificus-induced metabolic dysregulation.
• To understand the mechanisms of V. vulnificus proliferation and host immune evasion in skeletal muscle.

Main Methods:

• Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) for metabolome analysis.
• Comparative analysis of wild-type V. vulnificus and a MARTX deletion mutant in a mouse wound infection model.
• Assessment of bacterial proliferation and metabolite changes in infected skeletal muscle.

Main Results:

• V. vulnificus infection significantly altered muscle catabolites and energy metabolites, notably increasing succinic acid and decreasing fumaric acid.
• Deletion of the MARTX virulence factor abolished bacterial proliferation and associated metabolic changes in skeletal muscle.
• Immunosuppression (cyclophosphamide treatment) negated the difference in bacterial counts and metabolite levels between wild-type and MARTX mutant infections.

Conclusions:

• Vibrio vulnificus induces significant metabolic reprogramming in host skeletal muscle.
• The MARTX toxin plays a critical role in V. vulnificus proliferation and immune evasion within skeletal muscle.
• Understanding these metabolic shifts offers insights into severe V. vulnificus pathogenesis and potential diagnostic markers.