Colorectal cancer-associated Streptococcus gallolyticus: a hidden diversity expose

Area of Science:

• Microbiology and Genomics
• Cancer Research

Background:

• Streptococcus gallolyticus subsp. gallolyticus (SGG) is linked to bacteremia, endocarditis, and colorectal cancer (CRC).
• Intestinal dysbiosis, with increased SGG proportions, is associated with CRC development.
• Previous research identified specific genetic loci in other bacteria contributing to CRC.

Purpose of the Study:

• To sequence and analyze the genetic diversity of SGG clinical isolates from CRC patients.
• To identify potential pathogenicity factors specific to CRC-associated SGG strains.
• To compare SGG with its non-pathogenic relative, S. gallolyticus subsp. macedonicus.

Main Methods:

• Whole-genome sequencing of five novel and 30 additional SGG clinical isolates from CRC patients.
• Comparative genomics analysis against non-CRC isolates and S. gallolyticus subsp. macedonicus.
• Multilocus sequence typing (MLST), capsular loci, and pilus organization analysis.

Main Results:

• Unexpected genetic diversity was observed among CRC-associated SGG isolates; no specific pathogenicity island was identified.
• Most human-derived SGG isolates displayed multi-antibiotic resistance.
• SGG possesses a rich repertoire of surface proteins for polysaccharide binding and host colonization, C5a peptidase, bile salt hydrolase, and type VII secretion system effectors.

Conclusions:

• The association of SGG with CRC is complex, not attributable to a single strain or pathogenicity island.
• SGG's pathogenicity relies on a versatile set of surface proteins, immune evasion mechanisms, and gut persistence factors.
• Extracellular polysaccharides likely aid SGG survival in challenging environments.