Biology subjects

Rohn, J.

Publications and source records attributed to Rohn, J..

3 recordsLinked to original sources

bioRxiv2026

Gut-relevant short-chain fatty acids modulate host-pathogen dynamics of uropathogenic Escherichia coli at the colonic epithelial interface

Urinary tract infection (UTI) ranks among the most prevalent bacterial infections worldwide, affecting over 400 million people each year. Uropathogenic Escherichia coli (UPEC), the main aetiological cause of UTI, colonises the intestinal tract, which is thought to serve as a distal reservoir for gut-UTI recurrence. Despite this, the precise role of the gut in UTI recurrence is still not fully defined. Recent research investigating the gut-UTI axis has revealed that reduced abundance of gut commensals producing short-chain fatty acids (SCFAs, namely acetate, butyrate and propionate) is associated with recurrent and chronic UTI. We therefore aimed to investigate the impact of these gut commensal-derived metabolites on a diverse panel of UPEC strains, including well-studied prototypical strains (UTI89, CFT073), a non-pathogenic isolate E. coli K-12, and various clinical UTI isolates (from the urine of both symptomatic and asymptomatic individuals). We observed that SCFAs modulate bacterial growth kinetics in a concentration- and pH-dependent manner, by prolonging the lag phase without affecting final carrying capacity in vitro. These metabolites further suppressed bacterial swimming motility and biased the orientation of fimS, the phase variable switch for T1 fimbriae, under acidic conditions. In a human polarized, mucus-secreting intestinal infection model, SCFA treatment during UPEC challenge altered bacterial localization patterns, favouring planktonic over mucosal-associated populations, and preserved epithelial barrier function. Together, these in vitro findings demonstrate that SCFAs modulate key UPEC colonization-associated phenotypes and influence host-pathogen dynamics at the colonic epithelial interface. These results provide mechanistic insights into how depletion of SCFA-producing gut commensals may alter the intestinal reservoir environment in vitro and warrants further investigation into the role of gut-derived SCFAs in rUTI susceptibility.

microbiology↗

bioRxiv2025

Neutrophil myeloperoxidase as a functional biomarker for RSV severity: implications for in vitro therapeutic screening.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, yet effective therapeutics are lacking. The aim of this study is to develop an in vitro model that recapitulates key clinical outcomes in infants with RSV bronchiolitis to help accelerate the discovery of effective therapeutics. Neutrophil activation and influx into the airways are hallmarks of severe RSV infection, but these responses are difficult to quantify in clinical trials. Here we profile peripheral blood-derived neutrophils from infants with RSV admitted to the Paediatric Intensive Care Unit (PICU) and identify myeloperoxidase (MPO) as a key indicator of disease severity when compared to age matched controls. To mechanistically model this response, we established a paediatric airway epithelial air-liquid interface (ALI) system incorporating an endothelial layer and primary neutrophils to recapitulate the tissue microenvironment at the blood-airway barrier. Following RSV infection, neutrophil migration and activation were assessed using flow cytometry. The inclusion of an endothelial layer enhanced physiological relevance and more accurately replicated in vivo MPO responses. We then evaluated two antiviral candidates (remdesivir (RDV) and RSV604) to assess their ability to modulate neutrophil activation. While both compounds reduced viral load at 24 hours post-infection, only RSV604 attenuated MPO expression. These findings establish MPO as both a biomarker of RSV disease severity and a functional readout of therapeutic efficacy and demonstrate that targeting neutrophildriven inflammatory pathways may be critical for reducing pathology in infant RSV infection. Take home messageAntiviral drug discovery should include neutrophil MPO reduction as a readout of therapeutic efficacy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC="FIGDIR/small/682115v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@170058corg.highwire.dtl.DTLVardef@17c344corg.highwire.dtl.DTLVardef@14d79baorg.highwire.dtl.DTLVardef@172ac3c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Bidirectional Crosstalk Between Bladder Cancer Cells and Normal Fibroblasts Drives Phenotypic Reprogramming and Modulates Chemosensitivity

During early bladder cancer progression, invading tumour cells first encounter normal fibroblasts (NFs) residing in the lamina propria. Whether and how this interaction shapes tumour behaviour and treatment response, however, has not been systematically examined. While cancer-associated fibroblasts (CAFs) are established drivers of tumour progression and therapy resistance, the role of their precursor NFs in shaping bladder cancer behaviour has been largely overlooked. Here we dissect bidirectional interactions between bladder cancer cells and NFs using indirect (conditioned media) and direct co-culture systems. Fibroblast-conditioned media (FCM) significantly reduced proliferation while accelerating migration in both RT112 and T24 bladder cancer cells, consistent with a pro-migratory "go-or-grow" phenotypic shift. Immunofluorescence revealed FCM-induced cadherin switching reduced E-cadherin and elevated N-cadherin, indicative of an epithelial-to-mesenchymal transition (EMT)-like state. Reciprocally, NFs acquired CAF-like features within 48 hours of tumour cell exposure, with significant upregulation of SMA and FAP confirmed by both immunofluorescence and flow cytometry. Functionally, increasing fibroblast-to-cancer cell ratio progressively attenuated mitomycin C (MMC)-induced cytotoxicity, demonstrating a stromal-mediated, ratio-dependent protective effect against intravesical chemotherapy. Data from the Cancer Genome Atlas (TCGA) for Urothelial Bladder Carcinoma provided corroboratory evidence that fibroblast-enriched tumours exhibited a strong transcriptional correlation with EMT, elevated resistance-associated transcriptional signatures, and significantly poorer overall survival. Collectively, these findings establish tumour-NF crosstalk as a critical and bidirectional regulator of bladder cancer phenotypic plasticity and chemoresistance, and suggest that fibroblast-targeting strategies combined with intravesical chemotherapy may offer a rational approach to overcoming stromal-mediated treatment failure.

cancer biology↗