Engineered Bacterial Nanosyringes Induce Transient and Controllable Hepatic Immune-Metabolic Responses

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• The photorhabdus virulence cassette (PVC) is a bacterial nanodevice engineered for targeted protein delivery.
• Its effects on mammalian liver function and gene expression are not well understood.

Purpose of the Study:

• To investigate the impact of engineered PVCs on mammalian liver function and transcriptional networks.
• To assess potential hepatotoxicity and characterize the dynamic transcriptional response to PVC injection.

Main Methods:

• Engineered PVCs were administered intraperitoneally to BALB/c mice.
• Hepatic transcriptomes were analyzed using RNA sequencing (RNA-seq).
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed genes (DEGs).

Main Results:

• No acute hepatotoxicity was observed, evidenced by normal plasma ALT and AST levels.
• RNA-seq identified 6,471 DEGs, with early responses (2-4h) dominated by innate immune pathways (NF-κB, TNF, chemokine).
• Metabolic genes (CYP450, glutathione S-transferases) were downregulated at 12h but recovered by 24h, indicating transient effects.

Conclusions:

• Single intraperitoneal injection of PVC induces a transient and controllable immune-metabolic response in the liver.
• The nanodevice does not cause obvious acute hepatotoxicity.
• PVCs exhibit coordinated immune-metabolic dynamics, characterized by acute inflammation followed by metabolic reprogramming.