Flagellar switch inverted repeat sequence variation impacts Clostridioides difficile RT027/MLST1 virulence.
Nhu, N. T. Q.; Lin, H.; Sia, J. K.; Snitkin, E. S.; Young, V. B.; Kamboj, M.; Pamer, E. G.; Rice, P. A.; Dong, Q.
Show abstract
Clostridioides difficile RT027 strains cause infections that vary in severity from asymptomatic to lethal, but the molecular basis for this variability is poorly understood. Through comparative analyses of RT027 clinical isolates, we determined that isolates that exhibit greater variability in their flagellar gene expression exhibit greater virulence in vivo. C. difficile flagellar genes are phase-variably expressed due to the site-specific inversion of the flgB 5UTR region, which reversibly generates ON vs. OFF orientations for the flagellar switch. We found that longer inverted repeat (IR) sequences in this switch region correlate with greater disease severity, with RT027 strains carrying 6A/6T IR sequences exhibiting greater phenotypic heterogeneity in flagellar gene expression (60%-75% ON) and causing more severe disease than those with shorter IRs (> 99% ON or OFF). Taken together, our results reveal that phenotypic heterogeneity in flagellar gene expression may contribute to the variable disease severity observed in C. difficile patients.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genomic surveillance of vancomycin-resistant Enterococcus faecium reveals spread of a linear plasmid conferring a nutrient utilization advantage 95%
- Protection from lethal Clostridioides difficile infection via intraspecies competition for co-germinant 94%
- Genomic adaptation in group B Streptococcus following intrapartum antibiotic prophylaxis and childbirth 94%
Similar papers in this journal
- Phylogenomics of 8,839 Clostridioides difficile genomes reveals recombination-driven evolution and diversification of toxin A and B 95%
- Targeted IS-element sequencing uncovers transposition dynamics during selective pressure in enterococci 94%
- Unique growth and morphology properties of Clade 5 Clostridioides difficile strains revealed by single-cell time-lapse microscopy 94%
Similar papers in this journal
- Vibrio cholerae serotype impacts pathogenicity 96%
- Convergent within-host evolution alters key virulence factors in a Klebsiella pneumoniae clone during a large hospital outbreak 96%
- Genomic dissection of the bacterial population underlying Klebsiella pneumoniae infections in hospital patients: insights into an opportunistic pathogen 95%
Similar papers in this journal
- Clostridioides difficile-mucus interactions encompass shifts in gene expression, metabolism, and biofilm formation 95%
- The initial gut microbiota and response to antibiotic perturbation influence Clostridioides difficile colonization in mice 95%
- Clearance of Clostridioides difficile colonization is associated with antibiotic-specific bacterial changes 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.