Klebsiella pneumoniae LPS drives stromal-mediated repression of p53 and colorectal cancer chemoresistance

ABSTRACT: Evidence has emerged that the bacterial microbiota is a key modulator of colorectal cancer (CRC) response to therapy, but the molecular mechanisms of this interplay are poorly understood. Here, we investigate the effects of microbiota-driven signalling on the tumour suppressor p53 and its impact on chemotherapy. We uncover a mechanism by which lipopolysaccharide (LPS) from Klebsiella pneumoniae and other Enterobacteria impairs p53 activity and promotes chemoresistance via paracrine signalling from the tumour microenvironment. We observed that conditioned media from LPS-stimulated macrophages or fibroblasts suppressed p53 accumulation and attenuated the response to chemotherapeutic agents. Our data revealed selective inhibition of a subset of p53 targets by inflammation. This same subset negatively correlated with inflammatory signature and immune infiltration in patients and was associated with improved survival following chemotherapy. Our findings reveal a microbiota-driven mechanism of p53 suppression via the microenvironment that contributes to chemoresistance and highlight the impact of bacteria on tumour cell fate and therapeutic efficacy in CRC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Akos Vegvari  

LAB HEAD: Akos Vegvari

PROVIDER: PXD064521 | Pride | 2026-04-27

REPOSITORIES: Pride