In-host evolution of Yersinia enterocolitica during a chronic human infection

Area of Science:

• Microbiology
• Genomics
• Evolutionary Biology

Background:

• Bacteria demonstrate significant adaptability to environmental pressures like antibiotic treatment.
• Pathogenic bacteria can evolve within a host during prolonged infections.

Purpose of the Study:

• To characterize the genetic and phenotypic evolution of Yersinia enterocolitica during a 14-year chronic infection.
• To identify specific genetic mutations and proteomic changes associated with antibiotic resistance and in-host adaptation.

Main Methods:

• Whole-genome sequencing of sequential bacterial isolates.
• Proteomic analysis to assess protein expression and remodeling.
• Phenotypic testing for antibiotic susceptibility and growth characteristics.

Main Results:

• Identified genome reduction (approx. 100 genes lost) and a novel deletion in gyrA conferring quinolone resistance.
• Observed third-generation cephalosporin resistance linked to OmpF truncation and increased beta-lactamase production (BlaA, AmpC).
• Detected significant proteome remodeling, including perturbed stringent response and impaired metabolism, leading to in vitro growth defects.

Conclusions:

• Yersinia enterocolitica undergoes substantial genetic and phenotypic changes during prolonged in-host evolution under antibiotic pressure.
• These adaptations contribute to antibiotic tolerance and may explain therapeutic failures.
• The study highlights previously undocumented mechanisms of bacterial adaptation within a host environment.