Project description:<p>Mobile colistin resistance (mcr) genes undermine the efficacy of last-line polymyxin antibiotics, and the global prevalence of mcr-3 continues to rise despite reduced colistin use. Here, we show that mcr-3-positive Escherichia coli (E. coli) confers a survival advantage by reprogramming macrophage immunity. MCR-3-mediated lipid A modification blunted TLR4-NF-kappaB signaling, suppressed macrophage reactive oxygen species (ROS) generation, and delayed phagosome-lysosome fusion, allowing mcr-3-positive strains to evade intracellular killing. Integrated transcriptomic and metabolomic analyses revealed extensive immunometabolic rewiring in infected macrophages, including altered glycerophospholipid metabolism and iron homeostasis. Consistently, mcr-3 enhanced bacterial tolerance to ferrous iron stress, likely mitigating host-induced ferroptotic damage. In a mouse co-infection model, mcr-3-positive strains outcompeted isogenic mcr-3-negative strains under antibiotic treatment without any difference in antibiotic susceptibility in vitro. These findings reveal a dual-action mechanism that mcr-3 endows E. coli with both antibiotic resistance and host immune suppression, enabling persistence under antibiotic pressure and highlighting the long-term threat of mcr-3 dissemination even in the absence of polymyxin use.</p>
Project description:The purpose of this study is to determine whether the presence of pathogenic Escherichia coli in colon is associated with psychiatric disorders.
Project description:Despite the characterization of many aetiologic genetic changes. The specific causative factors in the development of sporadic colorectal cancer remain unclear. This study was performed to detect the possible role of Enteropathogenic Escherichia coli (EPEC) in developing colorectal carcinoma.
