Identifying resistance molecules in TiO₂ nanoparticle-tolerant strains to facilitate the development of strategies for combating TiO₂ nanoparticle pollution

The severity of environmental pollution caused by TiO₂ nanoparticles (nTiO₂) is increasing, highlighting the urgent need for the development of strategies to combat nTiO₂ pollution. Insights into resistance molecules from nTiO₂-tolerant strains may facilitate such development. In this study, we utilized multi-omics, genetic manipulation, physiological and biochemical experiments to identify relevant resistance molecules in two strains (Physarum polycephalum Z259 and T83) tolerated to mixed-phase nTiO₂ (MPnTiO₂). We discovered that a competing endogenous RNA (ceRNA) network, comprising one long non-coding RNA (lncRNA), four microRNAs, and nine mRNAs, influenced metabolic rearrangement and was associated with significant resistance in these strains. Additionally, we found that the lncRNA in the ceRNAs network and certain small-weight metabolites associated with the ceRNA exhibited notable mitigation effects not only against MPnTiO₂ but also against other types of nTiO₂ with broad species applicability (they significantly improved the resistance of several non-nTiO₂-tolerant cells/organisms in the laboratory and reduced cell damage of non-nTiO₂-tolerant cells/organisms in highly suspected nTiO₂-polluted areas of the real world). In summary, this study deepens our understanding of nTiO₂-tolerant strains, provides valuable insights into resistance molecules in these strains, and facilitates the development of strategies to combat nTiO₂ pollution.