Nanomaterial-microbe cross-talk: physicochemical principles and (patho)biological consequences.

The applications of nanoparticles (NPs) are increasing exponentially in consumer products, biotechnology and biomedicine, and humans, as well as the environment, are increasingly being exposed to NPs. Analogously, various (pathogenic) microorganisms are present at all the major exposure and entry sites for NPs in the human body as well as in environmental habitats. However, the field has just started to explore the complex interplay between NPs and microbes and the (patho)biological consequences. Based on recent insights, herein, we critically reviewed the available knowledge about the interaction of NPs with microbes and the analytical investigations including the latest intravital imaging tools. We have commented on how the NPs' characteristics influence complex formation with microorganisms, presented the underlying physicochemical forces, and provided examples of how this knowledge can be used to rationally control the NP-microbe interaction. We concluded by discussing the role of the biomolecule corona in NP-microbe crosstalk and speculated the impact of NP-microbe complex formation on the (patho)biological outcome and fate of microbial pathogens. The presented insights will not only support the field in engineering NPs with improved anti-microbial activity but also stimulate research on the biomedical and toxicological relevance of nanomaterial-microbiome complex formation for the anthropocene in general.

Taspase1: a 'misunderstood' protease with translational cancer relevance.

Proteolysis is not only a critical requirement for life, but the executing enzymes also play important roles in numerous pathological conditions, including cancer. Therefore, targeting proteases is clearly relevant for improving cancer patient care. However, to effectively control proteases, a profound knowledge of their mechanistic function as well as their regulation and downstream signalling in health and disease is required. The highly conserved protease Threonine Aspartase1 (Taspase1) is overexpressed in numerous liquid and solid malignancies and was characterized as a 'non-oncogene addiction' protease. Although Taspase1 was shown to cleave various regulatory proteins in humans as well as leukaemia provoking mixed lineage leukaemia fusions, our knowledge on its detailed functions and the underlying mechanisms contributing to cancer is still incomplete. Despite superficial similarity to type 2 asparaginases as well as Ntn proteases, such as the proteasome, Taspase1-related research so far gives us the picture of a unique protease exhibiting special features. Moreover, neither effective genetic nor chemical inhibitors for this enzyme are available so far, thus hampering not only to further dissect Taspase1's pathobiological functions but also precluding the assessment of its clinical impact. Based on recent insights, we here critically review the current knowledge of Taspase1's structure-function relationship and its mechanistic relevance for tumorigenesis obtained from in vitro and in vivo cancer models. We provide a comprehensive overview of tumour entities for which Taspase1 might be of predictive and therapeutic value, and present the respective experimental evidence. To stimulate progress in the field, a comprehensive overview of Taspase1 targeting approaches is presented, including coverage of Taspase1-related patents. We conclude by discussing future inhibition strategies and relevant challenges, which need to be resolved by the field.