Molecular omics最新文献

{"title":"Protein network analysis links the NSL complex to Parkinson’s disease via mitochondrial and nuclear biology†","authors":"Katie Kelly, Patrick A. Lewis, Helene Plun-Favreau and Claudia Manzoni","doi":"10.1039/D2MO00325B","DOIUrl":"https://doi.org/10.1039/D2MO00325B","url":null,"abstract":"<p >Whilst the majority of Parkinson’s Disease (PD) cases are sporadic, much of our understanding of the pathophysiological basis of the disease can be traced back to the study of rare, monogenic forms of PD. In the past decade, the availability of genome-wide association studies (GWAS) has facilitated a shift in focus, toward identifying common risk variants conferring increased risk of developing PD across the population. A recent mitophagy screening assay of GWAS candidates has functionally implicated the non-specific lethal (NSL) complex in the regulation of PINK1-mitophagy. Here, a bioinformatics approach has been taken to investigate the proteome of the NSL complex, to unpick its relevance to PD pathogenesis. The NSL interactome has been built, using 3 online tools: PINOT, HIPPIE and MIST, to mine curated, literature-derived protein–protein interaction (PPI) data. We built (i) the ‘mitochondrial’ NSL interactome exploring its relevance to PD genetics and (ii) the PD-oriented NSL interactome to uncover biological pathways underpinning the NSL/PD association. In this study, we find the mitochondrial NSL interactome to be significantly enriched for the protein products of PD-associated genes, including the Mendelian PD genes <em>LRRK2</em> and <em>VPS35</em>. In addition, we find nuclear processes to be amongst those most significantly enriched within the PD-associated NSL interactome. These findings strengthen the role of the NSL complex in sporadic and familial PD, mediated by both its mitochondrial and nuclear functions.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 8","pages":" 668-679"},"PeriodicalIF":2.9,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/mo/d2mo00325b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49995153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and metabolic signatures are fundamental to drought adaptation in PGPR Enterobacter bugandensis WRS7†","authors":"Saumya Arora, Piyoosh K Babele and Prabhat Nath Jha","doi":"10.1039/D3MO00051F","DOIUrl":"https://doi.org/10.1039/D3MO00051F","url":null,"abstract":"<p >Drought alone causes more annual loss in crop yield than the sum of all other environmental stresses. There is growing interest in harnessing the potential of stress-resilient PGPR in conferring plant resistance and enhancing crop productivity in drought-affected agroecosystems. A detailed understanding of the complex physiological and biochemical responses will open up the avenues to stress adaptation mechanisms of PGPR communities under drought. It will pave the way for rhizosphere engineering through metabolically engineered PGPR. Therefore, to reveal the physiological and metabolic networks in response to drought-mediated osmotic stress, we performed biochemical analyses and applied untargeted metabolomics to investigate the stress adaptation mechanisms of a PGPR <em>Enterobacter bugendensis</em> WRS7 (<em>Eb</em> WRS7). Drought caused oxidative stress and resulted in slower growth rates in <em>Eb</em> WRS7. However, <em>Eb</em> WRS7 could tolerate drought stress and did not show changes in cell morphology under stress conditions. Overproduction of ROS caused lipid peroxidation (increment in MDA) and eventually activated antioxidant systems and cell signalling cascades, which led to the accumulation of ions (Na<small>⁺</small>, K<small>⁺</small>, and Ca<small>²⁺</small>), osmolytes (proline, exopolysaccharides, betaine, and trehalose), and modulated lipid dynamics of the plasma membranes for osmosensing and osmoregulation, suggesting an osmotic stress adaption mechanism in PGPR <em>Eb</em> WRS7. Finally, GC–MS-based metabolite profiling and deregulated metabolic responses highlighted the role of osmolytes, ions, and intracellular metabolites in regulating <em>Eb</em> WRS7 metabolism. Our results suggest that understanding the role of metabolites and metabolic pathways can be exploited for future metabolic engineering of PGPR and developing bio inoculants for plant growth promotion under drought-affected agroecosystems.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 8","pages":" 640-652"},"PeriodicalIF":2.9,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49995152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology and fecal metabolomic analysis of the combinational mechanisms of Shexiang Baoxin Pill against atherosclerosis†","authors":"Zhicong Wang, Qianqian Wan, Bin Xie, Zifan Zhu, Xike Xu, Peng Fu and Runhui Liu","doi":"10.1039/D3MO00067B","DOIUrl":"10.1039/D3MO00067B","url":null,"abstract":"<p >Shexiang Baoxin Pill (SBP) has an excellent therapeutic effect on atherosclerosis (AS), but the combinational mechanisms of SBP against AS remain unclear. This study aimed to investigate the combinational mechanisms of SBP against AS by comprehensive network pharmacology and fecal metabolomic analysis. <em>Bufonis venenum</em>, one of the adjuvant medicines in SBP, is an animal medicine with a narrow therapeutic window. Considering animal protection, we evaluated the anti-AS effect of SBP without BV (SBP-BV) using <em>ApoE</em><small>^−/−</small> mouse models, culture cells, and metabolomic methods. Our data suggested that SBP showed remarkable anti-atherosclerotic effects through multiple targets and multiple pathways, while each component in SBP played different roles in their synergistic effect. Notably, SBP-BV showed comparable effects with SBP in the treatment of AS. Both SBP and SBP-BV could reduce cholesterol uptake in RAW264.7 cells and prevent the occurrence and development of AS in WD-induced <em>ApoE</em><small>^−/−</small> mice by attenuating the atherosclerotic plaque area, and reducing inflammatory cytokines and cholesterol levels <em>in vivo</em>. Our finding might provide new insights into the research and development of new anti-atherosclerosis drugs.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 8","pages":" 653-667"},"PeriodicalIF":2.9,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Analysis of N-glycosylation protein of Kashin–Beck disease chondrocytes derived from induced pluripotent stem cells based on label-free strategies with LC-MS/MS","authors":"Sen Wang, Peilin Meng, Linlin Yuan and Xiong Guo","doi":"10.1039/D3MO90016A","DOIUrl":"https://doi.org/10.1039/D3MO90016A","url":null,"abstract":"<p >Correction for ‘Analysis of <em>N</em>-glycosylation protein of Kashin–Beck disease chondrocytes derived from induced pluripotent stem cells based on label-free strategies with LC-MS/MS’ by Sen Wang <em>et al.</em>, <em>Mol. Omics</em>, 2023, https://doi.org/10.1039/d3mo00018d.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 514-514"},"PeriodicalIF":2.9,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/mo/d3mo90016a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49995591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Butyrate promotes C2C12 myoblast proliferation by activating ERK/MAPK pathway†","authors":"Li Guan, Ziyi Cao, Ziyue Pan, Chao Zhao, Mengjuan Xue, Fan Yang and Jie Chen","doi":"10.1039/D2MO00256F","DOIUrl":"10.1039/D2MO00256F","url":null,"abstract":"<p >Sarcopenia has garnered considerable interest in recent years as ageing-associated diseases constitute a significant worldwide public health burden. Nutritional supplements have received much attention as potential tools for managing sarcopenia. However, the specific nutrients responsible are still under-investigated. In the current study, we first determined the levels of short chain fatty acids (SCFAs) and intestinal flora in the feces of elderly sarcopenia subjects and elderly healthy individuals by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Then cell viability detection, flow cytometry and transcriptome analysis were adopted to experimentally evaluate the effect and the underlying mechanism of SCFA on C2C12 cells proliferation <em>in vitro</em>. The results suggested that patients with sarcopenia exhibited decreased levels of butyrate. And butyrate may stimulate C2C12 myocyte proliferation <em>via</em> promoting G1/S cell cycle transition. Transcriptomic analyses pointed to upregulation of the Mitogen-activated protein kinase (MAPK) signaling pathway in butyrate-treated cells. In addition, the above proliferative phenotypes could be suppressed by the combination of ERK/MAPK inhibitor. A combined transcriptomic and metabolomic approach was applied in our study to investigate the potential effect of microbiota-derived butyrate yield on muscular proliferation which may indicate a protective effect of nutritional supplements.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 7","pages":" 552-559"},"PeriodicalIF":2.9,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/mo/d2mo00256f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9984225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer†","authors":"Charles Ochieng’ Olwal, Jacqueline M Fabius, Lorena Zuliani-Alvarez, Manon Eckhardt, George Boateng Kyei, Peter Kojo Quashie, Nevan J Krogan, Mehdi Bouhaddou and Yaw Bediako","doi":"10.1039/D3MO00025G","DOIUrl":"10.1039/D3MO00025G","url":null,"abstract":"<p >Women coinfected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) are six times as likely to develop invasive cervical carcinoma compared to those without HIV. Unlike other HIV-associated cancers, the risk of cervical cancer development does not change when HPV/HIV coinfected women begin antiretroviral therapy, suggesting HIV-associated immune suppression is not a key driver of cervical cancer development in coinfected women. Here, we investigated whether the persistent secretion of inflammatory factors in HIV-positive patients on antiretroviral therapy could enhance cancer signaling in HPV-infected cervical cells <em>via</em> endocrine mechanisms. We integrated previously reported HIV-induced secreted inflammatory factors (Hi-SIFs), HIV and HPV virus–human protein interactions, and cervical cancer patient genomic data using network propagation to understand the pathways underlying disease development in HPV/HIV coinfection. Our results pinpointed the PI3K-AKT signaling pathway to be enriched at the interface between Hi-SIFs and HPV–host molecular networks, in alignment with PI3K pathway mutations being prominent drivers of HPV-associated, but HIV independent, cervical cancer development. Furthermore, we experimentally stimulated cervical cells with 14 Hi-SIFs to assess their ability to activate PI3K-AKT signaling. Strikingly, we found 8 factors (CD14, CXCL11, CXCL9, CXCL13, CXCL17, AHSG, CCL18, and MMP-1) to significantly upregulate AKT phosphorylation (pAKT-S473) relative to a phosphate buffered saline control. Our findings suggest that Hi-SIFs cooperate with HPV infection in cervical cells to over-activate PI3K-AKT signaling, effectively phenocopying PI3K-AKT pathway mutations, resulting in enhanced cervical cancer development in coinfected women. Our insights could support the design of therapeutic interventions targeting the PI3K-AKT pathway or neutralizing Hi-SIFs in HPV/HIV coinfected cervical cancer patients.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 7","pages":" 538-551"},"PeriodicalIF":2.9,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2023/mo/d3mo00025g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis of cancer dependency data and comprehensive phosphoproteomics data revealed the EPHA2-PARD3 axis as a cancer vulnerability in KRAS-mutant colorectal cancer†","authors":"Daigo Gunji, Ryohei Narumi, Satoshi Muraoka, Junko Isoyama, Narumi Ikemoto, Mimiko Ishida, Takeshi Tomonaga, Yoshiharu Sakai, Kazutaka Obama and Jun Adachi","doi":"10.1039/D3MO00042G","DOIUrl":"10.1039/D3MO00042G","url":null,"abstract":"<p >Colorectal cancer (CRC), a common malignant tumour of the gastrointestinal tract, is a life-threatening cancer worldwide. Mutations in KRAS and BRAF, the major driver mutation subtypes in CRC, activate the RAS pathway, contribute to tumorigenesis in CRC and are being investigated as potential therapeutic targets. Despite recent advances in clinical trials targeting KRASG12C or RAS downstream signalling molecules for KRAS-mutant CRC, there is a lack of effective therapeutic interventions. Therefore, understanding the unique molecular characteristics of KRAS-mutant CRC is essential for identifying molecular targets and developing novel therapeutic interventions. We obtained in-depth proteomics and phosphoproteomics quantitative data for over 7900 proteins and 38 700 phosphorylation sites in cells from 35 CRC cell lines and performed informatic analyses, including proteomics-based coexpression analysis and correlation analysis between phosphoproteomics data and cancer dependency scores of the corresponding phosphoproteins. Our results revealed novel dysregulated protein–protein associations enriched specifically in KRAS-mutant cells. Our phosphoproteomics analysis revealed activation of EPHA2 kinase and downstream tight junction signalling in KRAS-mutant cells. Furthermore, the results implicate the phosphorylation site Y378 in the tight junction protein PARD3 as a cancer vulnerability in KRAS-mutant cells. Together, our large-scale phosphoproteomics and proteomics data across 35 steady-state CRC cell lines represent a valuable resource for understanding the molecular characteristics of oncogenic mutations. Our approach to predicting cancer dependency from phosphoproteomics data identified the EPHA2-PARD3 axis as a cancer vulnerability in KRAS-mutant CRC.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 8","pages":" 624-639"},"PeriodicalIF":2.9,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9527232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP-1 inhibitor alleviates liver lipid accumulation of atherosclerosis via modulating bile acid metabolism and gut microbes†","authors":"Yingkun Sheng, Guibing Meng, Zhirong Zhou, Ruijiao Du, Yuefei Wang and Miaomiao Jiang","doi":"10.1039/D3MO00033H","DOIUrl":"https://doi.org/10.1039/D3MO00033H","url":null,"abstract":"&lt;p &gt; &lt;em&gt;Background&lt;/em&gt;: The DNA damage repair enzyme, poly(ADP-ribose) polymerase 1 (PARP1), is crucial for lipid and glucose metabolism. However, no evidence has been presented on the relationship between liver lipid accumulation and the PARP1 inhibitor, 3-aminobenzamide (3-AB), in atherosclerosis. &lt;em&gt;Methods&lt;/em&gt;: &lt;em&gt;ApoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice were used to explore the effect of 3-AB on atherosclerotic liver lipid accumulation, and the experiment of Sprague Dawley (SD) rats was designed to determine if the lowering of liver lipid levels by 3-AB was linked to gut bacteria. The levels of bile acid metabolism-related targets were assessed by ELISA, western blotting, and RT-qPCR. The relative abundances of gut microbes and biomarkers were determined using 16S rRNA sequencing analysis. Bile acid levels in the liver and ileum were examined by ultra-performance liquid chromatography-tandem mass spectrometry. The relationship between gut microbes and bile acids was assessed by Spearman's correlation analysis. &lt;em&gt;Results&lt;/em&gt;: 3-AB significantly reduced the formation of aortic plaques in &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice, according to gross oil red staining. H &amp; E and Oil Red O staining revealed that 3-AB significantly reduced the hepatic lipid droplet area in &lt;em&gt;ApoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice and SD rats. Compared with the atherosclerosis (ATH) group, 3-AB dramatically decreased the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) in the serum of SD rats and &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice, and the levels of TC, TG, and LDL-C in the serum and liver of &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice. Furthermore, in &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice and SD rats, 3-AB increased the mRNA and protein levels of farnesoid X receptor (FXR) and bile salt export pump (BSEP) in the liver, while inhibiting the mRNA and protein levels of FXR and fibroblast growth factor 15 (FGF15) in the ileum, respectively. 3-AB clearly inhibited the mRNA and protein levels of PARP1 in the liver and ileum of &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice and rats. Following treatment with 3-AB, the levels of conjugated bile acids decreased in the liver of &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice and increased in the ileum of SD rats, according to targeted metabolomic analysis. Microbiome sequencing analysis revealed that 3-AB reduced the relative abundance of &lt;em&gt;Lactobacillus&lt;/em&gt;, &lt;em&gt;Bifidobacterium&lt;/em&gt;, &lt;em&gt;Listeria&lt;/em&gt;, &lt;em&gt;Clostridium&lt;/em&gt;, &lt;em&gt;Bacillus&lt;/em&gt;, and &lt;em&gt;Staphylococcus&lt;/em&gt; in the feces of &lt;em&gt;apoE&lt;/em&gt;&lt;small&gt;&lt;sup&gt;−/−&lt;/sup&gt;&lt;/small&gt; mice, and the relative abundance of &lt;em&gt;Blautia&lt;/em&gt;, &lt;em&gt;Clostridium&lt;/em&gt;, and &lt;em&gt;Listeria&lt;/em&gt; in the feces of SD rats, eventually decreasing the total abundance of 10 bile salt hydrolase-associated gut microbes. According to the correlation analysis, 3-AB regulates bile acid metab","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 7","pages":" 560-573"},"PeriodicalIF":2.9,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49994737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and application of a data processing method for food metabolomics analysis†","authors":"Yuanluo Lei, Xiaoying Chen, Jiachen Shi, Yuanfa Liu and Yong-Jiang Xu","doi":"10.1039/D2MO00338D","DOIUrl":"10.1039/D2MO00338D","url":null,"abstract":"<p >Food metabolomics is described as the implementation of metabolomics to food systems such as food materials, food processing, and food nutrition. These applications generally create large amounts of data, and although technologies exist to analyze these data and different tools exist for various ecosystems, downstream analysis is still a challenge and the tools are not integrated into a single method. In this article, we developed a data processing method for untargeted LC-MS data in metabolomics, derived from the integration of computational MS tools from OpenMS into the workflow system Konstanz Information Miner (KNIME). This method can analyze raw MS data and produce high-quality visualization. A MS1 spectra-based identification, two MS2 spectra-based identification workflows and a GNPSExport-GNPS workflow are included in this method. Compared with conventional approaches, the results of MS1&amp;MS2 spectra-based identification workflows are combined in this approach <em>via</em> the tolerance of retention times and mass to charge ratios (<em>m</em>/<em>z</em>), which can greatly reduce the rate of false positives in metabolomics datasets. In our example, filtering with the tolerance removed more than 50% of the possible identifications while retaining 90% of the correct identification. The results demonstrated that the developed method is a rapid and reliable method for food metabolomics data processing.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 6","pages":" 464-472"},"PeriodicalIF":2.9,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9791598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct global metabolomic profiles of the model organism Caenorhabditis elegans during interactions with Staphylococcus aureus and Salmonella enterica Serovar Typhi†","authors":"Balasubramanian Chellammal Muthubharathi, Velayutham Ravichandiran and Krishnaswamy Balamurugan","doi":"10.1039/D3MO00040K","DOIUrl":"https://doi.org/10.1039/D3MO00040K","url":null,"abstract":"<p >The interactive network of hosts with pathogenic microbes is still questionable. It has been hypothesized and reported that the host shows altered regulatory mechanisms for different pathogens. Several studies using transcriptomics and proteomics revealed the altered pathways and sequential regulations displayed by the host during bacterial interactions. Still, there is a gap in understanding the triggering molecule at transcriptomic and proteomic levels due to the lack of the knowledge of the interactive metabolites produced during their interactions. In this study, the global metabolomic approach was performed in the nematode model organism <em>Caenorhabditis elegans</em> upon exposure to a Gram-negative bacteria, <em>Salmonella enterica</em> Serovar Typhi, and a Gram-positive bacteria, <em>Staphylococcus aureus</em>, and the whole metabolome was categorized as endo-metabolome (internally produced) and exo-metabolome (externally releasing). The extracted metabolites were subjected to liquid chromatography mass spectrometry (ESI-LC/qToF-MS/MS). In total 5578, 4554 and 4046 endo-metabolites and 4451, 3625 and 1281 exo-metabolites were identified in <em>C. elegans</em> when exposed to <em>E. coli</em> OP50, S. Typhi and <em>S. aureus</em>, respectively. Both the multivariate and univariate analyses were performed. The variation in endo- and exo-metabolome during candidate bacterial interactions was observed. The results indicated that, during <em>S. aureus</em> interaction, the exclusively enriched metabolites were significantly involved in alpha-linoleic acid metabolism. Similarly, the exclusively enriched metabolites during the interaction of S. Typhi were significantly involved in the phosphatidylinositol signalling system. The whole metabolomic profile presented here will build the scope to understand the role of metabolites and the respective pathways in host response during the early period of bacterial infections.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 7","pages":" 574-584"},"PeriodicalIF":2.9,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49994738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}