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

The severity of environmental pollution caused by TiO nanoparticles (nTiO) is increasing, highlighting the urgent need for the development of strategies to combat nTiO pollution. Insights into resistance molecules from nTiO-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 nTiO (MPnTiO). 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 MPnTiO but also against other types of nTiO with broad species applicability (they significantly improved the resistance of several non-nTiO-tolerant cells/organisms in the laboratory and reduced cell damage of non-nTiO-tolerant cells/organisms in highly suspected nTiO-polluted areas of the real world). In summary, this study deepens our understanding of nTiO-tolerant strains, provides valuable insights into resistance molecules in these strains, and facilitates the development of strategies to combat nTiO pollution.