Orientia tsutsugamushi modulates p53, the cell cycle, and genotoxicity to maintain its intracellular niche.

ABSTRACT: Infections by intracellular pathogens often cause insult to host cell DNA, which stimulates responses that ultimately eliminate the damaged cell and hence the microbial niche. p53 is an innate immunity mediator that responds to DNA damage and intracellular infection by transcriptionally activating pathways that arrest the cell cycle, repair DNA, and elicit apoptosis. How pathogens counter p53 are incompletely understood. Here, we demonstrate that the endotheliotropic obligate intracellular bacterium Orientia tsutsugamushi blocks transcription of TP53 to nearly deplete p53 levels. Contrary to the unrestricted proliferation expected based on the transcriptome of p53-deficient infected cells, Orientia arrests the cell cycle at S phase to promote bacterial replication. It protects host endothe

SUBMITTER: Allen PE 

PROVIDER: S-EPMC12365182 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature