Global expression profile of Enterhemorrhagic Escherichia coli O157:H7 in phagosome of murine macrophages
EHEC O157:H7 causes foodborne outbreaks leading to hemolytic uremic syndrome (HUS) via Shiga toxin (Stx). This study shows that a small percentage of phagocytized bacteria survive inside murine macrophage phagosomes. Using RNA-seq and multi-stress assays mimicking the phagosomal environment, the researchers found that macrophages attack bacteria with DNA damage, membrane damage, and nitric oxide (NO). In response, bacteria activate the SOS response, lipid biosynthesis, and NO detoxification, while conserving energy by downregulating flagella, T3SS, and T6SS. Notably, stx2a A subunit is upregulated inside phagosomes, but without the B subunit, suggesting transcriptional regulation rather than functional toxin production. Under in vitro multi-stress conditions (acidic pH, hydrogen peroxide), bacteria induce different pathways (acid resistance AR2-5, OxyR regulon) and show a more robust adaptive response, including stx1 induction via an SOS-independent route. The study highlights distinct bacterial transcriptional strategies against intracellular vs extracellular stress.