Manganese enhances macrophage bactericidal activity by repressing Sirt3 for Staphylococcus aureus osteomyelitis treatment
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ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Bowei Wang
PROVIDER: PXD076182 | iProX | Thu Mar 26 00:00:00 GMT 2026
REPOSITORIES: iProX
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Project description:Manganese (Mn) is an essential micronutrient critical for the pathogenesis of Staphylococcus aureus, a significant cause of human morbidity and mortality. Paradoxically, excess Mn is toxic, therefore maintaining intracellular Mn homeostasis is required for survival. To identify gene candidates that contribute to manganese detoxification, we compared the transcriptional response of S. aureus cells exposed to 1 mM MnCl2 and those that were untreated.
2019-01-01 | GSE124285 | GEO
Project description:We report the application of RNA-Seq analysis to determine the transcriptional responses to Mn dose, ranging from physiological to toxicological levels in human SH-SY5Y neuroblastoma cells. We find that Mn dose showed widespread effects in abundance of protein coding genes for metabolism of reactive oxygen species, energy sensing, glycolysis, protein homeostasis including the unfolded protein response and transcriptional regulation. Adaptive responses at physiological Mn concentration-10 μM Mn for 5 h, a concentration that did not result in cell death after 24 h increased abundance of differentially expressed genes (DEGs) in the protein secretion pathway that function in protein trafficking and cellular homeostasis.These include BET1 (Golgi vesicular membrane trafficking protein), ADAM10 (ADAM metallopeptidase domain 10) and ARFGAP3 (ADP-ribosylation factor GTPase activating protein 3). In contrast, 5 h exposure to 100 μM Mn, a concentration that caused cell death after 24 h, increased abundance of DEGs for components of the mitochondrial oxidative phosphorylation pathway. In conclusion, this study provides a framework for Mn dose dependent exposure in a human in vitro cell culture model and provides a testable hypothesis for in vivo studies. Importantly, the transcriptome responses at toxic Mn dose demonstrated patterns observed with neurological diseases and suggest that differential functions of the secretory pathway and mitochondria could provide a basis to improve detection and management of adverse environmental and occupational Mn exposures.
2019-06-20 | GSE129336 | GEO
Project description:Rats were exposed to manganese (Mn) at 25mg/kg for 15 days. After the exposure, the RNA was collected from the striatum tissue (specific part the brain) of the control group (untreated) and Mn-exposed group, and submitted for RNA sequencing to elucidate the transcriptional changes of Mn-induced toxicity in the striatum.
2020-10-01 | GSE153017 | GEO
Project description:Exposure to environmental pollutants, including heavy metals, during fetal life and early childhood, represents a major public health concern. While the health effects of exposure to a single metal have been well documented, real-life scenarios including simultaneous exposure to multiple metals have not yet been extensively investigated. In this study, we investigated the neurobehavioral effects and hippocampal transcriptomic alterations in mouse offspring developmentally exposed to lead (Pb), manganese (Mn), or their combination. Female mice were exposed to environmentally relevant low doses of Pb (100 ppm), Mn (2g/L), or both, via drinking water beginning two weeks prior to conception and continuing throughout gestation and lactation. Offspring of both sexes were assessed at multiple developmental stages using a comprehensive behavioral test battery to identify age- and sex-specific effects of exposure. For transcriptomic analysis, one male and one female (two month-old) from six litters per group (naive siblings of behaviorally tested mice) were euthanized for hippocampal tissue collection. Our novel finding was a specific deficit in social recognition in adult males developmentally exposed to Mn, an effect not observed in the Pb+Mn co-exposure group. To explore potential molecular mechanisms underlying the Mn-associated behavioral phenotype in males, we focused on differentially expressed genes (DEGs) with |logFC| > 1.5 and p < 0.01. Among these, Mup3 (major urinary protein 3) emerged as particularly notable due to its role in pheromonal communication and its potential link to the altered social investigation behaviors observed in Mn-exposed males. Overall, our behavioral data suggest that developmental exposure to Pb or Mn alone, but not in combination, elicits adverse neurobehavioral outcomes, particularly in males. Importantly, the pronounced effects of individual metal exposure, along with the apparent antagonistic interaction in the combined exposure group, were mirrored at the transcriptomic level.
2026-05-04 | GSE303190 | GEO
Project description:Manganese (Mn) is an essential trace element required for various biological functions, but excessive Mn levels are neurotoxic and lead to significant health concerns. The mechanisms underlying Mn-induced neurotoxicity remain poorly understood. Neuropathological studies of affected brain regions reveal astrogliosis, and neuronal loss, along with evidence of neuroinflammation. Here, we present a novel Mn-dependent mechanism linking mitochondrial dysfunction to neuroinflammation. We found that Mn disrupts mitochondrial transcriptome processing, resulting in the accumulation of complementary RNAs that form double-stranded RNA (dsRNA). This dsRNA is released to the cytoplasm, where it activates cytosolic sensor pathways, triggering type I interferon responses and inflammatory cytokine production. This mechanism is evident in 100-day human cerebral organoids, where Mn-induced inflammatory responses are observed predominantly in mature astrocytes. Similar effects were observed in the transcriptome and cytokine profile of female and male mouse brains carrying mutations in the SLC30A10 gene, a model of hypermanganesemia with dystonia1 disorder. These findings highlight a previously unrecognized role for mitochondrial dsRNA in Mn-induced neuroinflammation and provide insights into the molecular pathogenesis of manganism. We propose that this mitochondrial dsRNA-induced inflammatory pathway could be active in other diseases caused by environmental or genetic factors.
2026-06-08 | GSE316010 | GEO
Project description:ICP-MS analysis of Streptococcus pneumoniae D39 reveals a high cell-associated manganese (Mn(II)) concentration that is comparable to that of zinc (Zn(II)). Stressing these cells with 100-200 µM Zn(II) leads to a slow-growth phenotype and a reduction in total Mn(II) concentration, with no decrease in the concentrations of other metal ions. Supplementation of the growth media with as little as 10 µM Mn(II) fully restores wildtype growth patterns and normal levels of cell-associated Mn(II). DNA microarray analysis reveals that zinc stress induces the expected upregulation of czcD (encoding a zinc effluxer), but also a pleiotropic transcriptional response suggestive of mild cell wall stress. Genes encoding a nitric oxide detoxification system (nmlR) and the Mn(II) uptake system (psaABC) are also induced. We conclude that Zn(II) toxicity results in a cytoplasmic Mn(II) deficiency, possibly caused by competition at the Mn(II) uptake transporter protein PsaA.
2011-02-02 | GSE23504 | GEO
Project description:Manganese (Mn) stress is known to be a major limitation for development of soybean, and legume crop productivity globally. However, very little information is available on the adaptive mechanisms, particularly in the important legume crop soybean (Glycine Max L.), which enable leaves to respond to high-Mn availability. Thus, to elucidate these mechanisms in soybean leaves at molecular level, we used an RNA sequencing approach to investigate transcriptomes of the leaves under Mn-sufficient and Pi-excessive conditions. Our investigation revealed that more genes showed altered expression patterns in old leaf than in young leaf under Mn excess, suggesting that the Mn excess-more-sensitive old leaf required expression change in a larger number of genes to cope with high-Mn stress than the Mn excess-less-sensitive young leaf. The functional classification of differentially expressed genes (DEGs) was examined to gain an understanding of how leaves respond to Mn stress, caused by soil Mn excess. As a result, more DEGs involved in nodulation, detoxification, nutrient/ion transport, transcriptional factors, key metabolic pathways, Mn remobilization and signalling were found in Mn-excessive induced old leaves than in Mn-excessive induced young leaves. Our findings have enabled the identification of molecular processes that play important roles in the acclimation of leaves to Mn excess, ultimately leading to the development of Mn-efficient soybean suitable for Mn-excessive soils.
2022-08-16 | GSE118649 | GEO
Project description:Little is known about the latent infection period and lytic infection mechanism of pseudorabies virus. The advent of high-throughput sequencing technologies has allowed us to examine many different biological components simultaneously. To examine the effects of glucocorticoids on latently infected PRV neurons, we constructed gene expression profiles of RNA-seq data from PC-12 cell with a PRV latent infection model group (PRV group), a reactivation model group (DEX group) and a blank control group (CON group).
2025-05-02 | GSE202139 | GEO
Project description:Little is known about the latent infection period and lytic infection mechanism of pseudorabies virus. The advent of high-throughput sequencing technologies has allowed us to examine many different biological components simultaneously. To examine the effects of glucocorticoids on latently infected PRV neurons, we constructed gene expression profiles of RNA-seq data for miRNA expression from PC-12 cell with a PRV latent infection model group (PRV group), a reactivation model group (DEX group) and a blank control group (CON group).
2025-04-30 | GSE202138 | GEO
Project description:Despite its necessity, manganese (Mn) can causes phytotoxicity when present in excess. Stylo (Stylosanthes) is a dominant tropical legume with high Mn adaptability, but its Mn tolerance mechanisms are not well documented. This study integrated both physiological and transcriptome analyses of stylo in response to excess Mn toxicity. Results showed that stylo growth was decreased by excess Mn higher than 200 µM, as reflected by reductions in leaf chlorophyll and plant dry weight. Increases in enzyme activities of peroxidase (POD), ascorbate peroxidase (APX) and phenylalanine ammonia-lyase (PAL) and concentrations of secondary metabolites, including total phenols, flavonoids, tannins and anthocyanidins, were observed in stylo leaves at high Mn stress. Transcriptome analysis in stylo leaves resulted in identification of 2,471 up-regulated and 1,623 down-regulated genes under excess Mn toxicity. Among them, a set of differentially expressed genes (DEGs) involved in secondary metabolism, including PAL, chalcone synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS), were up-regulated in stylo under Mn toxicity, which were closely associated with the accumulation of secondary metabolites, suggesting that activation of secondary metabolism and corresponding gene expression might be important for stylo adaptation to Mn toxicity. Furthermore, a group of DEGs encoding transcription factors, such as genes belonged to C2H2 zinc finger transcription factor, WRKY, MYB and AP2 family, may be involved in stylo responses to Mn toxicity. Taken together, this study suggests that enhancing defense response and secondary biosynthesis pathway is adaptive strategy of stylo during Mn exposure, which might be regulated by complex transcriptional regulatory networks.
2020-12-08 | GSE147431 | GEO