Biology subjects

Kreuzer, M.

Publications and source records attributed to Kreuzer, M..

7 recordsLinked to original sources

bioRxiv2026

Multiscale mapping of venous remodelling in idiopathic pulmonary fibrosis

The integrity of the pulmonary vasculature is a key determinant of lung health, yet challenges in visualisation and quantification have hindered interrogation of its pathophysiological role in chronic lung disease. Here, we align recent advances in microscale image acquisition with novel computer vision-based vessel segmentation models to demonstrate expansion of the bronchial and pulmonary veins across varying severities of tissue remodelling in idiopathic pulmonary fibrosis (IPF). Relating these imaging findings to molecular data in control, mild, and severe fibrosis, we show that bronchial venous endothelial cells expand beyond their physiological peribronchial niche even in mild disease, acquiring persistent angiogenic, inflammatory, and matrix-remodelling programmes that define a specialised fibrovascular-immune interface. Finally, we relate these microscale and molecular observations to clinical CT imaging, demonstrating that intrapulmonary vein enlargement independently associates with worsened survival across three IPF cohorts. Collectively, our multimodal, multiscale approach connects previously unresolved three-dimensional venous architecture to its molecular endothelial correlate, establishing venous enlargement as a prognostically significant and clinically relevant feature of IPF. Our analytical approach also demonstrates how biological discoveries made in intact ex vivo human organs can translate into measurable phenotypes in living patients, providing a template for other organs and diseases.

pathology↗

bioRxiv2026

Pre-anaesthetic anxiety phenotype stratifies cortical excitability, learned navigation, and post-anaesthetic sleep in sevoflurane-exposed mice

Trait anxiety is a common pre-surgical phenotype and has been linked to adverse postoperative cognitive outcome, but whether it modulates the response to general anaesthesia has not been tested in a controlled design that isolates the anaesthetic from surgical injury. We classified 42 male C57BL/6N mice as low-anxiety (LA, n = 24) or high-anxiety (HA, n = 18) by unsupervised k-medoids clustering on cued fear-retrieval freezing, and exposed all animals to sevoflurane under live-EEG titration without surgery. At adequate anaesthetic depth, HA mice carried a flatter aperiodic (1/f) cortical slope than LA mice (AUC = 0.85, [0.70, 0.95]). Conventional water-cross-maze scoring returned null at post-anaesthetic re-test, but unsupervised decomposition of the same trial videos localised the effect to loss of a specific learned transition in HA mice (AUC = 0.72, [0.56, 0.86]). The dark-phase REMS response reversed direction, with HA mice losing REMS against their own baseline while LA mice gained it (AUC = 0.82, [0.65, 0.94]). The three effects are directionally consistent with modulation of cortical excitation-to-inhibition balance under sevoflurane. The aperiodic exponent and emergence-phase EEG trajectory, both recoverable from routine frontal EEG, are candidate pre-anaesthetic biomarkers.

neuroscience↗

bioRxiv2025

Synthetic communities of maize root bacteria interact and redirect benzoxazinoid metabolization

Plant roots are colonised by diverse microbial communities. These communities are shaped by root exudates including plant specialized metabolites. Benzoxazinoids are such secreted compounds of maize. Individual microbes differ in their ability to tolerate and metabolize antimicrobial benzoxazinoids. To investigate how these traits combine in a community, we designed two synthetic communities of maize root bacteria that share six common strains and differ in their ability to metabolize benzoxazinoids based on the seventh strain. We exposed both communities to the benzoxazinoid MBOA (6-methoxybenzoxazolin-2(3H)-one) and found that the metabolizing community did not degrade MBOA to its aminophenoxazinone, as observed for individual strains, but as a community they formed the corresponding acetamide. MBOA shaped differential compositions of both communities and increased the fraction of MBOA-tolerant strains. The benzoxazinoid metabolizing community showed a higher tolerance to MBOA and was able to utilize MBOA as their sole carbon source for growth. Hence, bacterial interaction results in alternative benzoxazinoid metabolization and increases community performance in presence of these antimicrobial compounds. Future work is needed to uncover the genetics of this metabolic interaction and ecological consequences for the bacterial community and the host plant. ImportanceWe investigated how maize root bacteria - alone or in community - tolerate and metabolize antimicrobial compounds of their host plant. We found the capacity to metabolize such a compound to impact bacterial community size and structure and most importantly, to beneeit community eitness. We also found that interacting bacteria redirected the metabolisation of the antimicrobial compound to an alternative degradation product. Our work highlights the need to study the team work of microbes to uncover their community traits to ultimately understand the ecological consequences for the bacterial community and eventually the host plant.

microbiology↗

bioRxiv2023

The lactonase BxdA mediates metabolic adaptation of maize root bacteria to benzoxazinoids

Root exudates contain secondary metabolites that affect the plants root microbiome. How microbes cope with these bioactive compounds, and how this ability shapes root microbiomes remain largely unknown. We investigated how maize root bacteria metabolise benzoxazinoids, the main specialised metabolites of maize. Diverse and abundant bacteria metabolised the major compound (6-methoxy-benzoxazolin-2-one, MBOA) in the maize rhizosphere to 2-amino-7-methoxyphenoxazin-3-one (AMPO). By contrast, bacteria isolated from Arabidopsis, which does not produce benzoxazinoids, were unable to metabolise MBOA. Among Microbacteria strains, this differential metabolisation allowed to identify a conserved gene cluster containing the lactonase bxdA. BxdA converts MBOA to AMPO in vitro and we show that this capacity provided bacteria a growth benefit under carbon-limiting conditions. Together these results reveal that maize root bacteria - through BxdA - are metabolically adapted to the benzoxazinoids of their host. We propose that metabolic adaptation to plant-specialised compounds shapes root bacterial communities across the plant kingdom.

microbiology↗

bioRxiv2023

Bacterial tolerance to host-exuded specialized metabolites structures the maize root microbiome

Plants exude specialized metabolites from their roots and these compounds are known to structure the root microbiome. However, the underlying mechanisms are poorly understood. We established a representative collection of maize root bacteria and tested their tolerance against benzoxazinoids, the dominant specialized and bioactive metabolites in the root exudates of maize plants. In vitro experiments revealed that benzoxazinoids inhibited bacterial growth in a strain- and compound-dependent manner. Tolerance against these selective antimicrobial compounds depended on bacterial cell wall structure. Further, we found that native root bacteria isolated from maize tolerated the benzoxazinoids better compared to non-host Arabidopsis bacteria. This finding suggests the adaptation of the root bacteria to the specialized metabolites of their host plant. Bacterial tolerance to 6-methoxy-benzoxazolin-2-one (MBOA), the most abundant and selective antimicrobial metabolite in the maize rhizosphere, correlated significantly with the abundance of these bacteria on benzoxazinoid-exuding maize roots. Thus, strain-dependent tolerance to benzoxazinoids largely explained the abundance pattern of bacteria on maize roots. Abundant bacteria generally tolerated MBOA, while low abundant root microbiome members were sensitive to this compound. Our findings reveal that tolerance to plant specialized metabolites is an important competence determinant for root colonization. We propose that bacterial tolerance to plant-secreted antimicrobial compounds is an underlying mechanism determining the structure of host-specific microbial communities. Significance StatementDiverse microbial communities colonize plant roots. They feed on carbon rich root exudates which contain a diverse mix of chemicals including primary and specialized metabolites. Here we show that specialized metabolites act as selective antibiotics to shape the root bacterial communities. By growing single isolates of maize root bacteria in the presence of benzoxazinoids in vitro, we find that the strains differ greatly in their tolerance to benzoxazinoids. Their different levels of tolerance largely explained their abundance on benzoxazinoid-exuding roots. Our work shows how plant specialized metabolites act to shape the maize root microbial community and thus deepened our mechanistic understanding of how plants shape their microbiome.

microbiology↗

bioRxiv2018

Microbiota stability in healthy individuals after single-dose lactulose challenge - a randomized controlled study

Background and aimsLactulose is a common food ingredient and widely used as a treatment for constipation or hepatic encephalopathy and a substrate for hydrogen breath tests. Lactulose is fermented by the colon microbiota resulting in the production of hydrogen (H2). H2 is a substrate for enteropathogens including Salmonella Typhimurium (S. Typhimurium) and increased H2 production upon lactulose ingestion might favor the growth of H2-consuming enteropathogens. We aimed to analyze effects of single-dose lactulose ingestion on the growth of intrinsic Escherichia coli (E. coli), which can be efficiently quantified by plating and which share most metabolic requirements with S. Typhimurium.\n\nMethods32 healthy volunteers (18 females, 14 males) were recruited. Participants were randomized for single-dose ingestion of 50 g lactulose or 50 g sucrose (controls). After ingestion, H2 in expiratory air and symptoms were recorded. Stool samples were acquired at days -1, 1 and 14. We analyzed 16S microbiota composition and abundance and characteristics of E. coli isolates.\n\nResultsLactulose ingestion resulted in diarrhea in 14/17 individuals. In 14/17 individuals, H2-levels in expiratory air increased by [≥]20 ppm within 3 hours after lactulose challenge. H2-levels correlated with the number of defecations within 6 hours. E. coli was detectable in feces of all subjects (2 x 102 - 109 CFU/g). However, the number of E. coli colony forming units (CFU) on selective media did not differ between any time point before or after challenge with sucrose or lactulose. The microbiota composition also remained stable upon lactulose exposure.\n\nConclusionIngestion of a single dose of 50 g lactulose does not significantly alter E. coli density in stool samples of healthy volunteers. 50 g lactulose therefore seems unlikely to sufficiently alter growth conditions in the intestine for a significant predisposition to infection with H2-consuming enteropathogens such as S. Typhimurium (www.clinicaltrials.gov NCT02397512).

microbiology↗

bioRxiv2018

Faster emergence behavior from ketamine/xylazine anesthesia with atipamezole versus yohimbine

Recent interest in reversal of the hypnotic effects of anesthesia has mainly focused on overcoming a surge in GABA-mediated inhibitory signaling through activation of subcortical arousal circuits or antagonizing GABA receptors. Here we examine the reversal of anesthesia produced from non-GABA agents ketamine/xylazine and the effects of antagonists of adrenoreceptors. These antagonists vary in selectivity and produce temporally unique waking behavior post-anesthesia. We compared two antagonists with differential selectivity for 1-vs. 2-receptors, yohimbine (YOH, 1:40 selectivity) and atipamezole (ATI, 1:8500). Adult mice received intraperitoneal injections of either YOH (4.3 mg/kg), ATI (0.4 mg/kg), or saline after achieving sustained loss of righting following injection of ketamine/xylazine (ketamine: 65.0 mg/kg; xylazine: 9.9 mg/kg). Behaviors indicative of the post-anesthesia, re-animation sequence were carefully monitored and the timing of each behavior relative to anesthesia induction was compared. Both YOH and ATI hastened behaviors indicative of emergence, but ATI was faster than YOH to produce certain behaviors, including whisker movement (YOH: 21.9{+/-}1.5 min, ATI: 17.5{+/-}0.5 min, p=0.004) and return of righting reflex (RORR) (YOH: 40.6{+/-}8.8 min, ATI: 26.0{+/-}1.2 min, p<0.001). Interestingly, although YOH administration hastened early behavioral markers of emergence relative to saline (whisking), the completion of the emergence sequence (time from first marker to appearance of RORR) was delayed with YOH. We attribute this effect to antagonism of 1 receptors by yohimbine. Also notable was the failure of either antagonist to hasten the re-establishment of coordinated motor behavior (e.g., attempts to remove adhesive tape on the forepaw placed during anesthesia) relative to the end of emergence (RORR). In total, our work suggests that in addition to pharmacokinetic effects, re-establishment of normal waking behaviors after anesthesia involves neuronal circuits dependent on time and/or activity.

neuroscience↗