A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors

• DOI: 10.1371/journal.ppat.1009182
• Publication Date: 2021-01-06T21:38:49Z
• Authors: John Culver Taylor; Xinsheng Gao; Juan Xu; Michael Holder; Joseph Petrosino; Ritesh Kumar; Wen Liu; Magnus Höök; Chris Mackenzie; Andrew Hillhouse; Wesley Brashear; Maria Patricia Nunez; Yi Xu
• Keywords: Pathogenicity island

Streptococcus gallolyticus subspecies ( Sgg ) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, molecular determinants involved in pathogenicity gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pathogen interactions their host important for virulence pathogenic mycobacteria Staphylococcus aureus . Through genome analysis, we identified locus strain TX20005 that encodes putative system (designated as T7SS T05 ). We showed core genes within expressed vitro mice. Western blot analysis EsxA, protein predicted to be substrate, is detected bacterial culture supernatant, indicating this functional. Deletion (TX20005Δ esx resulted impaired adherence HT29 cells abolished ability stimulate cell proliferation. Analysis supernatants suggest -secreted factors responsible pro-proliferative activity , whereas requires both surface-associated factors. In murine colonization model, TX20005Δ significantly reduced compared parent strain. Furthermore, mouse model CRC, mice exposed had higher tumor burden saline-treated mice, those did not. Examination load CRC suggests -mediated activities directly promotion Taken together, these results reveal previously unrecognized determinant