Polysaccharide lyase PL3.3 possibly potentiating Clostridioides difficile clinical symptoms based on complete genome analysis of RT046/ST35 and RT012/ST54

Int Microbiol. 2025 Jan 20. doi: 10.1007/s10123-025-00634-x. Online ahead of print.

Abstract

Clostridioides difficile has rapidly become a major cause of nosocomial infectious diarrhea worldwide due to the misuse of antibiotics. Our previous study confirmed that RT046/ST35 strain is associated with more severe clinical symptoms compared to RT012/ST54 strain. We conducted genome comparison of the RT046/ST35 and RT012/ST54 strains using whole-genome sequencing technology. The RT046/ST35 strain had a genome length of 7,869,254 bp with a GC content of 29.49%. The original length of the RT012/ST54 strain was 7,499,568 bp with a GC content of 29.64%. Additionally, we detected plasmid1 in the RT046/ST54 strain. We found that the RT046/ST35 strain had more genomic islands compared to the RT012/ST54 strain, and we identified polysaccharide lyase (PL) in the region around 2.2 M. Furthermore, we discovered that the increased severity of clinical symptoms in the RT046/ST35 strain compared to the RT012/ST54 strain was unrelated to virulence factors and emphasized the potential crucial role of PL in RT046/ST35. There were almost no differences in eggNOG annotation and KEGG annotation between RT046/ST35 and RT012/ST54. RT046/ST35 had more mRNA processes in GO annotation. In conclusion, our study suggests that the core factor contributing to the more serious clinical symptoms of the RT046/ST35 strain compared to the RT012/ST54 strain is possibly PL.

Keywords: Clostridioides difficile; Clinical symptom; Complete genome; Infection recurrence; Spore germination.