TY  - JOUR
A1  - Brachner, Andreas
A1  - Fragouli, Despina
A1  - Duarte, Iola F.
A1  - Farias, Patricia M. A.
A1  - Dembski, Sofia
A1  - Ghosh, Manosij
A1  - Barisic, Ivan
A1  - Zdzieblo, Daniela
A1  - Vanoirbeek, Jeroen
A1  - Schwabl, Philipp
A1  - Neuhaus, Winfried
T1  - Assessment of human health risks posed by nano-and microplastics is currently not feasible
JF  - International Journal of Environmental Research and Public Health
N2  - The exposure of humans to nano-and microplastic particles (NMPs) is an issue recognized as a potential health hazard by scientists, authorities, politics, non-governmental organizations and the general public. The concentration of NMPs in the environment is increasing concomitantly with global plastic production and the usage of plastic materials. NMPs are detectable in numerous aquatic organisms and also in human samples, therefore necessitating a risk assessment of NMPs for human health. So far, a comprehensive risk assessment of NMPs is hampered by limited availability of appropriate reference materials, analytical obstacles and a lack of definitions and standardized study designs. Most studies conducted so far used polystyrene (PS) spheres as a matter of availability, although this polymer type accounts for only about 7% of total plastic production. Differently sized particles, different concentration and incubation times, and various biological models have been used, yielding hardly comparable data sets. Crucial physico-chemical properties of NMPs such as surface (charge, polarity, chemical reactivity), supplemented additives and adsorbed chemicals have been widely excluded from studies, although in particular the surface of NMPs determines the interaction with cellular membranes. In this manuscript we give an overview about the critical parameters which should be considered when performing risk assessments of NMPs, including novel reference materials, taking into account surface modifications (e.g., reflecting weathering processes), and the possible role of NMPs as a substrate and/or carrier for (pathogenic) microbes. Moreover, we make suggestions for biological model systems to evaluate immediate toxicity, long-term effects and the potential of NMPs to cross biological barriers. We are convinced that standardized reference materials and experimental parameters along with technical innovations in (nano)-particle sampling and analytics are a prerequisite for the successful realization of conclusive human health risk assessments of NMPs.
KW  - nanoplastics
KW  - nanoparticles
KW  - microplastics
KW  - microparticles
KW  - human exposure
KW  - biological barriers
KW  - biofilm
KW  - microbe carrier
KW  - toxicity
KW  - neurotoxicity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219423
SN  - 1660-4601
VL  - 17
IS  - 23
ER  - 
TY  - JOUR
A1  - Barthels, Fabian
A1  - Marincola, Gabriella
A1  - Marciniak, Tessa
A1  - Konhäuser, Matthias
A1  - Hammerschmidt, Stefan
A1  - Bierlmeier, Jan
A1  - Distler, Ute
A1  - Wich, Peter R.
A1  - Tenzer, Stefan
A1  - Schwarzer, Dirk
A1  - Ziebuhr, Wilma
A1  - Schirmeister, Tanja
T1  - Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A
JF  - ChemMedChem
N2  - Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were found to have single‐digit micromolar Ki values and caused up to a 66 % reduction of S. aureus fibrinogen attachment at an effective inhibitor concentration of 10 μM. This new molecule class exhibited minimal cytotoxicity, low bacterial growth inhibition and impaired sortase‐mediated adherence of S. aureus cells.
KW  - antibiotics
KW  - biofilm
KW  - drug design
KW  - sortase A
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214581
VL  - 15
IS  - 10
SP  - 839
EP  - 850
ER  -