There is a risk that residues of antibiotics and other antimicrobials in hospital and municipal wastewaters could select for resistant bacteria. Still, direct experimental evidence for selection is lacking. Here, we investigated if effluent from a large Swedish hospital, as well as influent and effluent from the connected municipal wastewater treatment plant (WWTP) select for antibiotic resistant Escherichia coli in three controlled experimental setups.
View Article and Find Full Text PDFThe synthesis and antibacterial activity of two new highly truncated derivatives of the natural product abyssomicin C are reported. This work outlines the limits of structural truncation of the natural product and consequently provides insights for further structure-activity relationship studies towards novel antibiotics targeting 4-amino-4-deoxychorismate (ADC) synthase. Specifically, it is demonstrated that the synthetically challenging bicyclic motif is essential for activity towards methicillin-resistant (MRSA).
View Article and Find Full Text PDFThere is concern that sewage treatment plants (STPs) serve as hotspots for emergence and selection of antibiotic resistant bacteria. However, field studies investigating resistance selection by comparing bacterial populations in influents and effluents have produced variable and sometimes contradictive results. Also, large taxonomic changes between influents and effluents make interpretation of studies measuring relative gene abundances ambiguous.
View Article and Find Full Text PDFModulation of the elongation phase of protein synthesis is important for numerous physiological processes in both neurons and other cell types. Elongation is primarily regulated via eukaryotic elongation factor 2 kinase (eEF2K). However, the consequence of altering eEF2K activity on the synthesis of specific proteins is largely unknown.
View Article and Find Full Text PDFThe rapid regulation of cell signaling in response to calcium in neurons is essential for real-time processing of large amounts of information in the brain. A vital regulatory component, and one of the most energy-intensive biochemical processes in cells, is the elongation phase of mRNA translation, which is controlled by the Ca(2+)/CaM-dependent elongation factor 2 kinase (eEF2K). However, little is known about the dynamics of eEF2K regulation in neurons despite its established role in learning and synaptic plasticity.
View Article and Find Full Text PDFAlthough the MAP kinase-interacting kinases (MNKs) have been known for >15 years, their roles in the regulation of protein synthesis have remained obscure. Here, we explore the involvement of the MNKs in brain-derived neurotrophic factor (BDNF)-stimulated protein synthesis in cortical neurons from mice. Using a combination of pharmacological and genetic approaches, we show that BDNF-induced upregulation of protein synthesis requires MEK/ERK signaling and the downstream kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E.
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