Biology subjects

Stock, A.

Publications and source records attributed to Stock, A..

3 recordsLinked to original sources

bioRxiv2025

Ablation of polysaccharide breakdown in Bacteroides thetaiotaomicron prevents cross-feeding and growth of Salmonella Typhimurium in the mouse gut

Pathogens invading the intestine compete for nutrients with the resident microbiota. However, there is evidence that commensal members of the gut also provide nutritional resources to enteropathogens and thus promote their outgrowth. In this study, we investigated metabolic cross-feeding mechanisms between the abundant gut commensal Bacteroides thetaiotaomicron and the model enteropathogen Salmonella enterica serovar Typhimurium. We discovered that the processing of various dietary and host-derived glycans by B. thetaiotaomicron liberated building blocks available to Salmonella and identified a range of cross-fed metabolites. Interfering with polysaccharide degradation in B. thetaiotaomicron by genetic manipulation of specific polysaccharide utilization loci (PUL) inhibited pathogenic cross-feeding, both in vitro and in a gnotobiotic mouse model. Our findings highlight the complex metabolic commensal-pathogen interaction in the intestine and propose the disruption of polysaccharide breakdown as a potential microbiota-centric strategy to intervene in intestinal infections.

microbiology↗

bioRxiv2025

Expression of the Close homolog of L-1 and embigin identifies activated myofibroblasts.

AbstractFibrosis is driven by the emergence of myofibroblasts, which are the primary producers of the extracellular matrix proteins that form fibrotic lesions. Despite this critical role, detecting myofibroblasts remains challenging due to the paucity of selective markers. We therefore screened for novel myofibroblast-specific markers, discovering that the expression of the close homolog of L1 (ChL-1) and embigin (Emb) distinguish activated myofibroblasts from their quiescent precursors. We report that ChL-1+/Emb+ fibroblasts: (1) emerge during cardiac inflammation, (2) have elevated expression of collagens and inflammatory factors and (3) localise to fibrotic zones - consistent with activated myofibroblasts. Mechanistically, Chl1+/Emb+ myofibroblasts differentiate from resident fibroblasts which upregulate these markers in response to proinflammatory cytokines, such as IL-1 and IL-17. Moreover, we show that embigin could be exploited to target antibody-based therapies to myofibroblasts and confirm this protein as a conserved marker of activated fibroblasts in multiple tissues and settings. Collectively, these findings identify ChL-1 and embigin as novel myofibroblast surface-markers that could be used to identify, enumerate and target this pathogenic population.

cell biology↗

bioRxiv2023

mTOR signaling controls the formation of smooth muscle cell-derived intimal fibroblasts during vasculitis.

The excessive accumulation of fibroblasts within the intimal layer of inflamed vessels is a feared complication of vasculitis, which can lead to arterial stenosis and ischemia. In this study, we have investigated how such intimal fibroblasts develop during Kawasaki Disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that vasculitis-induced intimal fibroblasts develop independently of both adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived intimal fibroblasts - in both mice and in patients with KD, Takayasus arteritis and Giant Cell arteritis - coincided with their activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, the genetic deletion of mTOR signalling in SMCs abrogated the emergence of intimal fibroblasts, demonstrating that mTOR is an intrinsic and essential regulator of vasculitis-induced, SMC-derived intimal fibroblasts. Collectively these findings provide molecular insight into the pathogenesis of arterial stenosis and identify mTOR as a therapeutic target to prevent adverse vascular remodelling in vasculitis.

cell biology↗