Biology subjects

Hahn, V.

Publications and source records attributed to Hahn, V..

4 recordsLinked to original sources

bioRxiv2026

Natural variation in soybean perception of bacterial quorum-sensing signals shapes primed defense

Plants perceive N-acyl homoserine lactones (AHLs), the quorum-sensing signals of rhizobacteria, and can translate them into a primed state of enhanced inducible immunity. Whether this perception-to-defense translation varies heritably among genotypes is largely unknown. Using soybean (Glycine max) responses to N-3-oxo-tetradecanoyl-L-homoserine lactone (oxo-C14-HSL), with root invasion by the nematode Pratylenchus penetrans as a quantitative challenge revealing the primed state, we tested whether AHL-triggered priming is genotype-dependent. Priming with the oxo-C14-HSL-producing rhizobacterium Ensifer meliloti ExpR+ potentiated defense in the responsive cultivar Primus, reducing nematode invasion (P < 0.001), but not in the weakly responsive Sigalia (P = 0.082). The purified molecule reproduced this contrast, localizing the difference to signal transduction within the plant rather than bacterial colonization. Correspondingly, the phytoalexin glyceollin accumulated in a priming- and challenge-dependent manner in Primus but not Sigalia, the formal signature of priming. Across a Sigalia x Primus recombinant inbred line population and an independent diversity panel, responsiveness was heritable, continuously distributed, and transgressive. Two genome-wide association studies and a cross-population meta-analysis converged on a well-calibrated null, indicating a polygenic or strongly environment-dependent architecture rather than a common-variant, large-effect-size model. Translating a bacterial signal into primed defense is thus a quantitatively varying plant trait.

microbiology↗

bioRxiv2025

Time-resolved effects of cold atmospheric plasma on E. coli GW-AmxH19 transcriptome and proteome in an emulated wastewater environment

Cold atmospheric plasma (CAP) has been shown to be effective against a variety of microorganisms. In this study, we described effects on an Escherichia coli strain isolated from hospital wastewater caused by a treatment with physical plasma. E. coli GW-AmxH19 was incubated in artificial wastewater and treated for 15 minutes with CAP. Transcriptomes and proteomes were monitored at different timepoints within a 24 h period to differentiate between immediate physiological responses and adaptations in the recovery phase. Reduction of viable cells was on average at 90%. The short-term response of the surviving cells to physical plasma aims at repairing and protecting cellular structures from plasma-induced damages, mainly provoked by reactive oxygen and nitrogen species. Notably, CAP induced a temporary transcription of genes from a conjugative plasmid carrying antibiotic resistance determinants. The late response during recovery phase is dominated by a massive activation of two prophages turning cold plasma treatment into a novel possible strategy to induce the lytic cycle of prophages. This study is the first report on the combined analysis of transcriptional and translational effects of CAP on an environmental bacterial isolate in a time-resolved manner. Chances and risks of considering CAP as an additional purification step in wastewater treatment plants are depicted and discussed.

microbiology↗

bioRxiv2024

ATP Citrate Lyase Supports Cardiac Function and NAD+/NADH Balance And Is Depressed in Human Heart Failure

BackgroundATP-citrate lyase (ACLY) converts citrate into acetyl-CoA and oxaloacetate in the cytosol. It plays a prominent role in lipogenesis and fat accumulation coupled to excess glucose, and its inhibition is approved for treating hyperlipidemia. In RNAseq analysis of human failing myocardium, we found ACLY gene expression is reduced; however the impact this might have on cardiac function and/or metabolism has not been previously studied. As new ACLY inhibitors are in development for cancer and other disorders, such understanding has added importance. MethodsCardiomyocytes, ex-vivo beating hearts, and in vivo hearts with ACLY inhibited by selective pharmacologic (BMS303141, ACLYi) or genetic suppression, were studied. Regulation of ACLY gene/protein expression, and effects of ACLYi on function, cytotoxicity, tricarboxylic acid (TCA)-cycle metabolism, and redox and NAD+/NADH balance were assessed. Mice with cardiac ACLY knockdown induced by AAV9-acly-shRNA or cardiomyocyte tamoxifen-inducible Acly knockdown were studied. ResultsAcly gene expression was reduced more in obese patients with heart failure and preserved EF (HFpEF) than HF with reduced EF. In vivo pressure-overload and in vitro hormonal stress increased ACLY protein expression, whereas it declined upon fatty-acid exposure. Acute ACLYi (1-hr) dose-dependently induced cytotoxicity in adult and neonatal cardiomyocytes, and caused substantial reduction of systolic and diastolic function in myocytes and ex-vivo beating hearts. In the latter, ATP/ADP ratio also fell and lactate increased. U13C-glucose tracing revealed an ACLY-dependent TCA-bypass circuit in myocytes, where citrate generated in mitochondria is transported to the cytosol, metabolized by ACLY and then converted to malate to re-enter mitochondria, bypassing several NADH-generating steps. ACLYi lowered NAD+/NADH ratio and restoring this balance ameliorated cardiomyocyte toxicity. Oxidative stress was undetected with ACLYi. Adult hearts following 8-weeks of reduced cardiac and/or cardiomyocyte ACLY downregulation exhibited ventricular dilation and reduced function that was prevented by NAD augmentation. Cardiac dysfunction from ACLY knockdown was worse in hearts subjected to sustained pressure-overload, supporting a role in stress responses. ConclusionsACLY supports normal cardiac function through maintenance of the NAD+/NADH balance and is upregulated by hemodynamic and hormonal stress, but depressed by lipid excess. ACLY levels are most reduced in human HFpEF with obesity potentially worsening cardio-metabolic reserve.

molecular biology↗

bioRxiv2021

PDE9 Inhibition Activates PPARa to Stimulate Mitochondrial Fat Metabolism and Reduce Cardiometabolic Syndrome

Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show inhibiting cyclic-GMP selective phosphodiesterase-9A (PDE9-I) suppresses established diet-induced obesity and CMS in ovariectomized female and male mice. PDE9-I reduces abdominal, hepatic, and myocardial fat accumulation, stimulates mitochondrial activity in brown and white fat, and improves CMS, without altering activity or food intake. PDE9 localizes to mitochondria, and its inhibition stimulates lipolysis and mitochondrial respiration coupled to PPAR-dependent gene regulation. PPAR upregulation is required for PDE9-I metabolic efficacy and is absent in non-ovariectomized females that also display no metabolic benefits from PDE9-I. The latter is compatible with estrogen receptor- altering PPAR chromatin binding identified by ChIPSeq. In humans with heart failure and preserved ejection fraction, myocardial expression of PPARA and its regulated genes is reduced versus control. These findings support testing PDE9-I to treat obesity/CMS in men and postmenopausal women. SummaryOral inhibition of phosphodiesterase type 9 stimulates mitochondrial fat metabolism and lipolysis, reducing central obesity without changing appetite

physiology↗