The symbiotic system of ATP translocase-expressing bacteria (ATEB) and macrophages.

The endosymbiosis theory indicates that mitochondria evolved from free-living prokaryotes, which entered host cells and remained as endosymbionts. Here we have designed an Escherichia coli - macrophage symbiosis system. By engineering and modifying Escherichia coli to enter cells through membrane fusion, it can bypass lysosomes to avoid being degraded by cells and exist stably in macrophages. Moreover, it has been genetically engineered to express ATP. This symbiotic bacterium can serve as a mitochondrial substitute to provide the energy necessary for the metabolism of life activities of host macrophages. By up-regulating the genes related to tricarboxylic acid cycle and oxidative phosphorylation and down-regulating the genes related to glycolysis, it significantly enhances the metabolic activity of host macrophages. This symbiotic system can still exist within 60 hours and can still maintain certain functionality in the microenvironment of tumor nutritional deficiency. Overall design: RAW264.7cells were co-cultured for 24 h. Total RNA was extracted using RNAiso plus reagent (TaKaRa Biomedical Technology Co., Ltd), and then RNA quality was determined by 5300 bioanalyzer (Agilent). RNA purification, reverse transcription, library construction, and sequencing were performed at Genecreate Biotechnology Co., LTD. (Wuhan, China) in accordance with the manufacturer's instructions. Cell transcriptomic data analysis was performed on the Genecreate Biotechnology cloud platform (China).