Biology subjects

Somogyi, A.

Publications and source records attributed to Somogyi, A..

6 recordsLinked to original sources

bioRxiv2026

A preclinical resistance framework discovers the virulence risks of antibiotics in development

Several new antibiotics target multidrug-resistant pathogens, yet resistance is still evaluated mainly by drug-susceptibility, leaving consequences for bacterial pathogenicity poorly understood. Here, we develop a framework integrating resistance evolution, genomic surveillance and host-pathogen phenotyping to classify antibiotics by resistance potential and pathogenic consequences. Applying this framework to Klebsiella pneumoniae identified functionally distinct antibiotic candidates associated with elevated virulence risk. Resistance evolution rapidly increased virulence through clinically-relevant mutations, without direct selection for pathogenicity. Despite distinct genetic routes, resistance converged on cell-envelope rewiring. A single resistance mutation increased epithelial adhesion, intracellular colonization, macrophage immune-evasion, and tissue persistence in murine infection models, transforming K. pneumoniae into a more invasive and cytotoxic pathogen. Risk-profile analysis revealed partial decoupling of resistance and pathogenicity, with some low-resistance antibiotics yielding highly-virulent populations. These findings establish resistance-driven virulence as an underappreciated translational hazard and call for incorporating host-pathogen interactions into resistance surveillance and preclinical antibiotic development.

microbiology↗

bioRxiv2026

NRAMP2 controls manganese partitioning between seed coat and embryo to regulate seed vigor

Seed development and germination depend on the coordinated transport of macronutrients and micronutrients, which sustain the embryo and determine seed vigour. Manganese (Mn) is an essential micronutrient involved in various metabolic processes, yet its role in seed development is not well understood. In this study, we investigated manganese (Mn) homeostasis in seeds and identified NRAMP2, a previously characterised trans-Golgi-localised Mn exporter, as a key transporter that controls Mn delivery to the embryo. Promoter analysis showed NRAMP2 expression in the chalazal region, which is a central hub for the exchange of nutrients between maternal tissues and the developing seed. X-ray fluorescence mapping revealed mislocalisation of Mn in nramp2 mutant seeds, retention of Mn on the seed coat and markedly reduced levels of Mn in the embryo. Functionally, Mn depletion delayed seed germination and increased physiological dormancy by reducing reactive oxygen species (ROS) accumulation. Our results uncover the vital role of Mn in supporting embryo development and seed vigour, establishing NRAMP2 as a pivotal component of the Mn transport machinery during seed development.

plant biology↗

bioRxiv2025

Food supplementation with molybdenum complexes improves honey bee health

In this study, we evaluated the impact of supplementing honey bee feed with molybdenum-based compounds. Among a dozen of dinuclear Mo(V) complexes, we first selected the most stable and non-toxic complexes, which were tested as food supplements in an extensive eight-year campaign involving more than 700 beehives across various environmental conditions in Moldova, France, Greece and USA. This unprecedented field campaign revealed that a few milligrams of compounds Na-Mo2O4-EDTA or Li-Mo2O4-EDTA provided in spring or autumn, increased queen fecundity, hygienic behavior, and honey production, while infestation rates of worker bees and brood by the mite Varroa destructor, and mortality rates in winter were dramatically reduced. Hive monitoring showed that the Mo-containing syrup can be consumed over 1.5 months and is well assimilated by larvae and workers within the hive. In particular, Mo levels increased significantly in the head of the bees. X-ray fluorescence measurements demonstrated that Na-Mo2O4-EDTA increases Mo levels in brain, neurolemma and hypopharyngeal glands. The metabolism of Mo complexes was addressed using X-Ray photoelectron spectroscopy (XPS) on bee faeces, which revealed that the complexes are oxidized into Mo(VI) species and thus suggesting that Mo complexes may function as antioxidant agents in bees. These findings offer promising solutions for the beekeeping industry, which is struggling with weakening honey bee colonies. Significance StatementHoney bees play a crucial role as pollinators. Unfortunately, colony losses have increased significantly over the past decades through the action of multiple environmental stressors. Currently, solutions are sought to strengthen bees health and resilience. This study shows that feeding bees with small amounts of trace elements like molybdenum can improve honey bee condition and increase the production of hive products. Through an unprecedented series of field and lab tests it notably demonstrates that molybdenum complexes are i) non-toxic, ii) consumed by bees over several generations, iii) assimilated particularly in the brain and hypopharyngeal glands, iv) acting as antioxidant. These results open new avenues for using trace elements to improve pollinator health.

zoology↗

bioRxiv2024

Storage and transport of labile iron is mediated by lysosomes in axons and dendrites of hippocampal neurons

Iron dyshomeostasis in neurons, involving iron accumulation and abnormal redox balance, is implicated in neurodegeneration. In particular, labile iron, a highly reactive pool of intracellular iron, plays a prominent role in iron-induced neurological damage. However, the mechanisms governing the detoxification and transport of labile iron within neurons are not fully understood. This study investigates the storage and transport of labile ferrous iron Fe(II) in cultured primary rat hippocampal neurons. Iron distribution was studied using live cell confocal microscopy with a selective labile Fe(II) fluorescent dye, and synchrotron X-ray fluorescence microscopy (SXRF) for total iron distribution. Fluorescent labelling of the axon initial segment and of lysosomes allowed iron distribution to be correlated with these subcellular compartments. The results show that labile Fe(II) is stored in lysosomes within somas, axons and dendrites and that lysosomal labile Fe(II) is transported retrogradely and anterogradely along axons and dendrites. In addition, we have developed a methodological workflow to quantify labile Fe(II) relative to total iron in neurites. This method is based on correlative imaging of fluorescence microscopy of labile Fe(II) combined with quantitative elemental mapping of total iron by SXRF. Quantitative analysis revealed that after Fe(II) exposure, lysosomal Fe(II) accounts for a small but significant percentage of the total iron content in neurites. These result suggest that after exposure to labile Fe(II), iron is mainly present in a non-reactive form in neurons, while the smaller fraction of reactive labile Fe(II) is stored in lysosomes and can be transported along dendrites and axons.

neuroscience↗

bioRxiv2021

Catabolism of lysosome-related organelles in color-changing spiders supports intracellular turnover of pigments

Pigment organelles of vertebrates belong to the lysosome-related organelle (LRO) family, of which melanin-producing melanosomes are the prototypes. While their anabolism has been extensively unraveled through the study of melanosomes in skin melanocytes, their catabolism remains poorly known. Here, we tap into the unique ability of crab spiders to reversibly change body coloration to examine the catabolism of their pigment organelles. By combining ultrastructural and metal analyses on high-pressure frozen integuments, we first assess whether pigment organelles of crab spiders belong to the LRO family and, second, how their catabolism is intracellularly processed. Using scanning-transmission electron microscopy, electron tomography and nanoscale Synchrotron-based scanning X-ray fluorescence, we show that pigment organelles possess ultrastructural and chemical hallmarks of LROs, including intraluminal vesicles and metal deposits, similar to melanosomes. Monitoring ultrastructural changes during bleaching suggests that the catabolism of pigment organelles involves the degradation and removal of their intraluminal content, possibly through lysosomal mechanisms. In contrast to skin melanosomes, anabolism and catabolism of pigments proceed within the same cell without requiring either cell death or secretion/phagocytosis. Our work hence provides support for the hypothesis that the endolysosomal system is fully functionalized for within-cell turnover of pigments, leading to functional maintenance under adverse conditions and phenotypic plasticity. First formulated for eye melanosomes in the context of human vision, the hypothesis of intracellular turnover of pigments gets unprecedented strong support from pigment organelles of spiders.

cell biology↗

bioRxiv2020

Cytoplasmic aggregation of uranium in human dopaminergic cells after continuous exposure to soluble uranyl at non-cytotoxic concentrations

Uranium exposure can lead to neurobehavioral alterations in particular of the monoaminergic system, even at non-cytotoxic concentrations. However, the mechanisms of uranium neurotoxicity after non-cytotoxic exposure are still poorly understood. In particular, imaging uranium in neurons at low intracellular concentration is still very challenging. We investigated uranium intracellular localization by means of synchrotron X-ray fluorescence imaging with high spatial resolution (< 300 nm) and high analytical sensitivity (< 1 g.g-1 per 300 nm pixel). Neuron-like SH-SY5Y human cells differentiated into a dopaminergic phenotype were continuously exposed, for seven days, to a non-cytotoxic concentration (10 M) of soluble natural uranyl. Cytoplasmic submicron uranium aggregates were observed accounting on average for 62% of the intracellular uranium content. In some aggregates, uranium and iron were co-localized suggesting common metabolic pathways between uranium and iron storage. Uranium aggregates contained no calcium or phosphorous indicating that detoxification mechanisms in neuron-like cells are different from those described in bone or kidney cells. Uranium intracellular distribution was compared to fluorescently labeled organelles (lysosomes, early and late endosomes) and to fetuin-A, a high affinity uranium-binding protein. A strict correlation could not be evidenced between uranium and the labelled organelles, or with vesicles containing fetuin-A. Our results indicate a new mechanism of uranium cytoplasmic aggregation after non-cytotoxic uranyl exposure that could be involved in neuronal defense through uranium sequestration into less reactive species. The remaining soluble fraction of uranium would be responsible for protein binding and the resulting neurotoxic effects.

pharmacology and toxicology↗