Biology subjects

Hobson, C.

Publications and source records attributed to Hobson, C..

3 recordsLinked to original sources

bioRxiv2026

Collective protection drives human gut microbiota response to amoxicillin treatment.

The gut microbiota is central to human health, contributing to nutrient processing, metabolite production and protection against pathogens. Yet it is also an unintended target of antibiotic treatments, particularly after oral administration. Antibiotic exposure can therefore disrupt community structure, leading to dysbiosis and promoting the selection of resistant bacteria. Although studies in patients and animal models have shown that these effects vary markedly between individuals, host-related factors have made it difficult to isolate the specific contribution of the microbiota itself. Here, we used a controlled in vitro gut model (MBRA) to examine how 16 human gut microbiotas from the NutriNet-Sante cohort respond to the widely prescribed {beta}-lactam amoxicillin (AMX). By combining dense temporal sampling, 16S amplicon sequencing and mass spectrometry, we observed highly heterogeneous response trajectories, ranging from near-stable communities to strong but reversible disruptions. These differences were not only reflected in the final magnitude of perturbation, but also in the timing, pace and recovery of microbiota change during treatment. Initial community composition partly structured these responses, as Lachnospiraceae/Bacteroidaceae ratio strongly correlated with perturbation. Dynamic quantification of AMX further showed that microbiotas differed in their capacity to deplete the drug over time, thereby altering the duration of exposure above critical concentration thresholds. Supplementation with clavulanic acid that inhibits {beta}-lactamases confirmed that this process was largely mediated by {beta}-lactamase activity. Finally, microbiotas displaying rapid AMX depletion showed reduced selection of resistant Enterobacteriaceae. Together, our results indicate that both initial community composition and the temporal dynamics of antibiotic inactivation jointly determine microbiota resilience and resistance selection.

microbiology↗

bioRxiv2026

Measuring Amorphous Motion: Application of Optical Flow to Three-Dimensional Fluorescence Microscopy Images

Motion is an essential component of any living system. It is rich with information, but it is often challenging to quantitatively extract biologically informative results from the motion apparent in microscopy images. This challenge is exacerbated by the wide variety in biological movement, which often takes the form of difficult-to-segment amorphous structures undergoing complex motion. An image processing technique known as optical flow can capture motion at each pixel in an image, thus bypassing the need for object segmentation or a priori definition of motion types. This makes it a powerful tool for quantitative assessment of biological systems from the protein to organism scale. However, despite its flexibility and strengths for analyzing fluorescence microscopy images, its adoption in the bioimaging community has been limited by the availability of easy-to-use tools and guidance in results interpretation. Here we describe an optical flow tool, OpticalFlow3D, that can be run in Python or MATLAB and is compatible with three-dimensional microscopy images. Using biological examples across length scales, we illustrate how OpticalFlow3D can enable new biological insight.

bioinformatics↗

bioRxiv2023

Antibiotic skeletal diversification via differential enoylreductase recruitment and module iteration in trans-acyltransferase polyketide synthases

Microorganisms are remarkable chemists capable of assembling complex molecular architectures that penetrate cells and bind biomolecular targets with exquisite selectivity. Consequently, microbial natural products have wide-ranging applications in medicine and agriculture. How the "blind watchmaker" of evolution creates skeletal diversity is a key question in contemporary natural products research. Comparative analysis of biosynthetic pathways to structurally related metabolites is an insightful approach to addressing this. Here we report comparative biosynthetic investigations of gladiolin, a polyketide antibiotic from Burkholderia gladioli with promising activity against multidrug resistant Mycobacterium tuberculosis, and entangien, a structurally related antibiotic produced by Sorangium cellulosum. Although these metabolites have very similar macrolide cores, their C21 side chains differ significantly in both length and degree of saturation. Surprisingly, the trans-acyltransferase polyketide synthases (PKSs) that assemble these antibiotics are almost identical, raising intriguing questions about mechanisms underlying structural diversification in this important class of biosynthetic assembly line. In vitro reconstitution of key biosynthetic transformations using simplified substrate analogues, combined with gene deletion and complementation experiments, enabled us to elucidate the origin of all structural differences in the C21 side chains of gladiolin and etnangien. The more saturated gladiolin side chain arises from a cis-acting enoylreductase (ER) domain in module 1 and in trans recruitment of a standalone ER to module 5 of the PKS. Remarkably, module 5 of the gladiolin PKS is intrinsically iterative in the absence of the standalone ER, accounting for the longer side chain in etnangien. These findings have important implications for biosynthetic engineering approaches to the creation of novel polyketide skeletons.

biochemistry↗