Insights on Recurrent and Sequential Clostridioides difficile Infections From Genomic Surveillance in Minnesota, USA,...

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Clostridioides difficile infection (CDI) frequently recurs, posing challenges in treatment and management.
• Recurrence can stem from relapse with the same strain or reinfection with a new strain.
• Understanding the genetic basis of recurrent CDI is crucial for developing effective interventions.

Purpose of the Study:

• To assess the genetic diversity and molecular evolution of C. difficile strains causing recurrent or sequential CDI.
• To differentiate between relapse and reinfection as causes of CDI recurrence using whole-genome sequencing (WGS).

Main Methods:

• Analysis of isolates from 306 patients with multiple CDI events (2019-2021) via population and laboratory surveillance.
• Whole-genome sequencing (WGS) to identify multi-locus sequence types (MLSTs), nucleotide variants, and mobile genetic elements (MGEs).
• Comparative genomic analysis of sequential C. difficile isolates within patients.

Main Results:

• Most recurrent CDI events (64.7%) involved the same multi-locus sequence type (MLST), suggesting relapse or evolution of the same strain.
• No significant correlation was found between accumulated mutations and time between same-MLST CDI events.
• Mobile genetic elements (MGEs) were gained or lost in 45.6% of sequential same-MLST C. difficile genome pairs, indicating strain evolution.

Conclusions:

• Recurrent CDI is a complex interplay of reinfection, strain selection in mixed infections, and relapse.
• This study expands knowledge on the evolutionary dynamics of C. difficile within the human gastrointestinal tract.
• WGS provides critical insights into the mechanisms driving CDI recurrence.