bioRxiv Science⌕ Search

Biology subjects

Westphal, V.

Publications and source records attributed to Westphal, V..

2 recordsLinked to original sources

Suppressing selection for antibiotic resistance in the environment: A transparent, ecology-based approach to predicted no-effect concentrations

Selection for antibiotic resistance has been demonstrated at low, environmentally-relevant antibiotic concentrations. Over the past decade, the concept of minimum selective concentrations (MSC) has been adopted in environmental regulation to define maximum permissible antibiotic concentrations. Such empirically determined MSC values often fail to reflect the complexity of natural communities, where susceptibility and resistance-associated fitness costs vary widely across species. To address this limitation, computational approaches have been developed to predict no-effect concentrations for selection of antibiotic resistance (PNECres) from routinely collected minimum inhibitory concentration (MIC) data. However, these approaches often lack a strong ecological basis, undermining confidence in their predictions. Here, we propose a simple but biologically consistent framework to derive PNECres values by integrating MIC data with probabilistic estimates of resistance-related fitness costs. Our results suggest that current regulatory environmental threshold concentrations should be lowered by at least one order of magnitude to guard against selection for antibiotic resistance.

microbiology↗

MINFLUX fluorescence nanoscopy in biological tissue

Optical imaging access to nanometer-level protein distributions in intact tissue is a highly sought-after goal, as it would provide visualization in physiologically relevant contexts. Under the unfavorable signal-to-background conditions of increased absorption and scattering of the excitation and fluorescence light in the complex tissue medium, super-resolution fluorescence microscopy methods are severely challenged in attaining precise localization of molecules. We reasoned that the typical use of a confocal detection pinhole in MINFLUX nanoscopy, suppressing background and providing optical sectioning, should facilitate the detection and resolution of single fluorophores even amid scattering and optically challenging tissue environments. Here, we investigated the performance of MINFLUX imaging for different synaptic targets and fluorescent labels in tissue sections of the mouse brain. Single fluorophores were localized with a precision of < 5 nm at up to 80 {micro}m sample depth. MINFLUX imaging in two color channels allowed to probe PSD95 localization relative to the spine head morphology, while also visualizing presynaptic VGlut clustering and AMPA receptor clustering at the post-synapse. Our two-dimensional (2D) and three-dimensional (3D) two-color MINFLUX results in tissue, with < 10 nm 3D fluorophore localization, open up new avenues to investigate protein distributions on the single-synapse level in fixed and living brain slices.

biophysics↗