Chronic Exposure to Titanium Dioxide Nanoparticles Induces Commensal-to-Pathogen Transition in Escherichia coli

Due to daily exposure to nanostructured titanium dioxide (nTiO2) for various purposes, concerns have been raised regarding the potential health impact of this material. Few studies have researched the chronic effect of nTiO2 on commensal gut bacteria, and the exposure scenario is typified by long durations, low doses, and dark conditions. We repeatedly exposed Escherichia coli to 5 mg/L nTiO2 for 200 subcultures (400 days) in the dark. Adaptive morphogenesis (i.e., filamentation, thickening of the cell wall, and biofilm formation) was observed, which diminished the sensitivity of the cells to oxidative stress and multiple antibiotics. The bacterial mobility was enhanced by approximately 66%, which was ascribed to the significant increases in flagellar assembly and fimbria biosynthesis. These adaptive traits were associated with increased pathogenicity, as corroborated by a higher death rate of macrophages in vitro and more severe bacterial infection in mice in vivo. The adaptive evolution was attributed to hydroxyl radical production by 5 mg/L nTiO2 in the dark due to surface oxygen vacancies. Therefore, although nTiO2 is generally considered inert in the absence of light, additional precautions should be taken when it is applied in food and daily products considering its potential toxic effects on the commensal microbial community.