Pathoadaptive mutations in Salmonella enterica isolated after serial passage in mice

Area of Science:

• Microbiology
• Evolutionary Biology
• Genomics

Background:

• Pathogenic bacteria evolution within hosts is complex.
• Understanding Salmonella Typhimurium adaptation is crucial for disease control.

Purpose of the Study:

• Identify mutations enabling Salmonella Typhimurium adaptation to mouse systemic growth.
• Quantify the competitive advantage conferred by specific adaptive mutations.

Main Methods:

• Whole genome sequencing of serially passaged Salmonella Typhimurium LT2 populations.
• Competition experiments in mice using wild-type and mutant strains.
• Analysis of flagellar gene regulation and expression.

Main Results:

• Pathoadaptive mutations were identified in global regulators phoQ and stpA, increasing bacterial competitive index 3-5 fold.
• All adapted lineages inverted the hin element, switching flagellum production to FliC type, yielding a 5-fold competitive advantage.
• Combined mutations in hin and stpA increased competitive index up to 20-fold.

Conclusions:

• Salmonella Typhimurium rapidly adapts to the mouse environment through acquiring mutations.
• Mutations in global regulators and flagellar type switching provide substantial growth advantages.
• Combined moderate-effect mutations lead to significant increases in bacterial fitness during host infection.