Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose radical-mediated TiO2 photocatalytic action of such nanocomposites and evaluate the genome/proteome-wide expression profiles of Pseudomonas aeruginosa PAO1 cells after two minutes of intervention. The results indicate that the impact on the gene-wide flux distribution and metabolism is moderate in the analysed time span. Rather, the photocatalytic action triggers the decreased expression of a large array of genes/proteins specific for regulatory, signalling and growth functions in parallel with subsequent selective effects on ion homeostasis, coenzyme-independent respiration and cell wall structure. The present work provides the first solid foundation for the biocidal action of titania and may have an impact on the design of highly active photobiocidal nanomaterials.

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The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such as PHD3, which in turn increases the stability of hypoxia-inducible factor (HIF)-1α. In the present study, we identify the serine/threonine kinase DYRK2 as SIAH2 interaction partner that phosphorylates SIAH2 at five residues (Ser16, Thr26, Ser28, Ser68, and Thr119). Phosphomimetic and phospho-mutant forms of SIAH2 exhibit different subcellular localizations and consequently change in PHD3 degrading activity. Accordingly, phosphorylated SIAH2 is more active than the wild-type E3 ligase and shows an increased ability to trigger the HIF-1α-mediated transcriptional response and angiogenesis. We also found that SIAH2 knockdown increases DYRK2 stability, whereas SIAH2 expression facilitates DYRK2 polyubiquitination and degradation. Hypoxic conditions cause a SIAH2-dependent DYRK2 polyubiquitination and degradation which ultimately also results in an impaired SIAH2 phosphorylation. Similarly, DYRK2-mediated phosphorylation of p53 at Ser46 is impaired under hypoxic conditions, suggesting a molecular mechanism underlying chemotherapy resistance in solid tumors.