Biology subjects

Becker, S. L.

Publications and source records attributed to Becker, S. L..

5 recordsLinked to original sources

bioRxiv2026

Pathogen-driven reactivation of metabolite prodrugs defines nitroxoline's iron-deprivation antibiotic activity

The rise of antimicrobial resistance warrants renewed attention to established but overlooked antibiotics such as nitroxoline (NTX). Here, we systematically dissect NTXs mode of action and investigate the contribution of its first-pass metabolites, NTX-sulphate and NTX-glucuronide. We identified metallophore-mediated cellular iron deprivation as the principal antibacterial mechanism of NTX, characterized by induction of iron acquisition pathways and Fe-S cluster proteins, and concomitant loss of protein-bound iron. In contrast, NTX metabolites were biologically inactive and lacked metal-chelating properties. Ex vivo assays demonstrated that clinically relevant uropathogens, including Escherichia coli and Klebsiella pneumoniae, efficiently reconvert these metabolites into active NTX in human urine. Together, our findings establish a mechanistic framework linking NTX antibacterial activity, host detoxification, and pathogen-dependent metabolite reactivation, and providing a molecular explanation for NTXs enduring therapeutic potential and favourable safety profile.

microbiology↗

bioRxiv2025

Tracheal tuft cell-released leukotrienes promote antibacterial immune responses

Tuft cells act as crucial sentinels in the airways that detect bacterial metabolites. In response, tuft cells release signaling molecules that trigger immune responses essential for clearing the infection. The molecular mechanisms driving immune cell activation following tuft cell stimulation in pneumonia are still not fully understood. Here, we identify tuft cells as the primary source of proinflammatory leukotrienes (LTs), which are released in the presence of pathogenic bacteria in the airways. We show that tracheal tuft cells discriminate pathogenic from non-pathogenic bacteria by sensing adenosine triphosphate (ATP) released from pathogens such as Pseudomonas aeruginosa and Rodentibacter pneumotropicus within the first 4 h of invasion, and recruit neutrophils and macrophages to the trachea and alveolar spaces. Taste signaling through the chemosensory transient receptor potential cation channel subfamily M member 5 (Trpm5) channel was essential for tuft cell activation and LT release. Mice lacking Trpm5 were not capable of detecting bacteria-released ATP and became colonized upon R. pneumotropicus infection. In contrast, Trpm5+/+ mice cleared the pathogen. We uncover a critical tuft cell-dependent sensing mechanism in pneumonia and establish tracheal tuft cells as both detectors of bacterial extracellular ATP and triggers of acute innate immune responses.

immunology↗

bioRxiv2025

Extracellular vesicles and their RNA cargo facilitate bidirectional cross-kingdom communication between human and bacterial cells

While extracellular vesicles (EVs) are established mediators of intra-species signaling, their role as active participants in cross-kingdom communication remains incompletely understood. Here, we reveal that human colon cells and both Gram-positive and Gram-negative gut bacteria engage in species-specific, EV-mediated molecular dialogue, driven in part by RNA cargo. We show that bacterial EVs (BEVs) induce distinct transcriptomic responses in human cells, and that BEV-RNA independently causes similar effects. Conversely, we demonstrate that human EVs and highly abundant miR-192-5p are differentially internalized by bacteria, affecting their physiology. Our findings support a conceptual model in which EVs function as directional messengers that shape host-microbiome interactions. This study introduces a framework for understanding EVs as cross-kingdom regulators and underscores the importance of tailored, context-specific analyses for understanding the scope of EV-mediated interactions in microbiome-host homeostasis and disease. Highlights[1] L. casei, E. faecalis and P. mirabilis produce BEVs that are internalized by Caco-2 cells at different rates. BEVs produced by L. casei have a positive influence on the viability of Caco-2 cells. Incubation of Caco-2 cells with BEVs leads to changes in the gene expression of immune-response-related genes. [2] BEVs carry RNAs and the type of RNA cargo varies significantly between the BEVs from the different bacteria. Comparison of Caco-2 gene deregulation between BEVs and transfection of RNA isolated from BEV highlights component-specific effects. [3] Caco-2 EVs are taken up by E. faecalis and influence their growth. MiRNA-192-5p can be frequently detected in EVs from Caco-2 cells. Synthetic miR-192-5p is internalized by P. mirabilis and the ability to take up human miRNAs by L. casei and E. faecalis can be increased by packaging of the miRNA in artificial liposomes.

molecular biology↗

bioRxiv2025

Joint bacterial traces in the gut and oral cavity of Colitis patients provide evidence for saliva as rich microbial biomarker source

The human microbiome, distributed across various anatomical sites, holds promise for identifying diagnostic biomarkers and therapeutic targets in disease. In inflammatory bowel disease (IBD), including ulcerative colitis (UC), interactions between the gut and oral microbiomes are crucial for understanding disease mechanisms and guiding interventions. The IMAGINE study sequenced 1,931 specimens from saliva, plaque, stool, and other sources in patients and healthy controls. Here, we assess whether the oral (saliva/plaque) or gut microbiota provides greater diagnostic potential in IBD and examine shared dysregulation across sample types. Among 177 oral samples (102 healthy, 75 IBD) and 92 stool samples (57 healthy, 35 IBD), we identified 240 distinct strains in plaque, 229 in saliva, and 231 in stool, with 46 strains present in all three. Saliva showed a significantly higher average effect size (0.2) than stool (0.04) and plaque (0.06). Notably, Actinomyces sp., Bifidobacterium dentium, and Veillonella parvula exhibited increased effect sizes, suggesting their potential as diagnostic markers or therapeutic targets. These findings indicate that microbiome profiling in IBD may improve diagnostics and treatment strategies.

microbiology↗

bioRxiv2023

Time series of chicken stool metagenomics and egg metabolomics in changing production systems

Different production systems of livestock animals influence various factors, including the gut microbiota. We investigated whether changing the conditions from barns to free-range impacts the microbiome over the course of three weeks. We compared the stool microbiota of chicken from industrial barns after introducing them either in community or separately to a free-range environment. Over the six time points, 12 taxa - mostly lactobacilli - changed significantly. As expected, the former barn chicken cohort carries more resistances to common antibiotics. These, however, remained positive over the observed period. At the end of the study, we collected eggs and compared metabolomic profiles of the egg white and yolk to profiles of eggs from commercial suppliers. Here, we observed significant differences between commercial and fresh collected eggs as well as differences between the former barn chicken and free-range chicken. Our data suggest that the gut microbiota can change over time following a change in production systems. This change also influences the metabolites in the eggs. We understand the study as a proof-of-concept that justifies larger scale observations with more individual chicken and longer observation periods.

zoology↗