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Flagellar switch inverted repeat impacts flagellar invertibility and varies Clostridioides difficile RT027/MLST1
Nguyen T Q Nhu1,2, Huaiying Lin2, Ying Pigli3
1Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Biorxiv : the Preprint Server for Biology
|October 10, 2024
Summary
Clostridioides difficile RT027 strains show varied virulence due to flagellar gene expression. Longer DNA repeats in the flagellar switch correlate with greater disease severity and phenotypic heterogeneity.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Clostridioides difficile (C. diff) RT027 strains cause infections with unpredictable severity.
- The molecular mechanisms driving this variability in C. diff virulence remain unclear.
Purpose of the Study:
- To investigate the relationship between flagellar gene expression variability and virulence in C. diff RT027 clinical isolates.
- To identify genetic factors influencing flagellar gene expression heterogeneity.
Main Methods:
- Comparative analysis of C. diff RT027 clinical isolates.
- Examination of flagellar gene expression patterns.
- Correlation analysis between genetic features (inverted repeat sequences) and virulence phenotypes.
Main Results:
- Greater variability in flagellar gene expression correlated with increased virulence in vivo.
- Flagellar gene expression is phase-variable, controlled by inversion of the flgB 5'UTR region.
- Longer inverted repeat (IR) sequences in the switch region (6A/6T) were associated with greater phenotypic heterogeneity (60%-75% ON) and more severe disease compared to shorter IRs (>99% ON or OFF).
Conclusions:
- Phenotypic heterogeneity in flagellar gene expression contributes to the variable disease severity observed in C. diff infections.
- The length of IR sequences in the flagellar switch region is a key determinant of C. diff virulence and expression variability.
