{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:21:27Z","timestamp":1785903687054,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T00:00:00Z","timestamp":1371168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leafy gall is a plant hyperplasia induced upon Rhodococcus fascians infection. Previously, by genomic and transcriptomic analysis, it has been reported that, at the early stage of symptom development, both primary and secondary metabolisms are modified. The present study is based on the hypothesis that fully developed leafy gall, could represent a potential source of new bioactive compounds. Therefore, non-targeted metabolomic analysis of aqueous and chloroform extracts of leafy gall and non-infected tobacco was carried out by 1H-NMR coupled to principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Polar metabolite profiling reflects modifications mainly in the primary metabolites and in some polyphenolics. In contrast, main modifications occurring in non-polar metabolites concern secondary metabolites, and gas chromatography and mass spectrometry (GC-MS) evidenced alterations in diterpenoids family. Analysis of crude extracts of leafy galls and non-infected tobacco leaves exhibited a distinct antiproliferative activity against all four tested human cancer cell lines. A bio-guided fractionation of chloroformic crude extract yield to semi-purified fractions, which inhibited proliferation of glioblastoma U373 cells with IC50 between 14.0 and 2.4 \u00b5g\/mL. Discussion is focused on the consequence of these metabolic changes, with respect to plant defense mechanisms following infection. Considering the promising role of diterpenoid family as bioactive compounds, leafy gall may rather be a propitious source for drug discovery.<\/jats:p>","DOI":"10.3390\/ijms140612533","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T11:47:47Z","timestamp":1371210467000},"page":"12533-12549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Metabolomic-Based Study of the Leafy Gall, the Ecological Niche of the Phytopathogen Rhodococcus fascians,  as a Potential Source of Bioactive Compounds"],"prefix":"10.3390","volume":"14","author":[{"given":"Aminata","family":"Nacoulma","sequence":"first","affiliation":[{"name":"Laboratory of Toxicology, Faculty of Pharmacy, Universit\u00e9 Libre de Bruxelles, CP 205\/1, Boulevard du Triomphe, Brussels B-1050, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Vandeputte","sequence":"additional","affiliation":[{"name":"Laboratory of Plant Biotechnology, Faculty of Sciences, Universit\u00e9 Libre de Bruxelles,  12 rue des Professeurs Jeener et Brachet, Gosselies B-6041, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuella","family":"De Lorenzi","sequence":"additional","affiliation":[{"name":"Laboratory of Toxicology, Faculty of Pharmacy, Universit\u00e9 Libre de Bruxelles, CP 205\/1, Boulevard du Triomphe, Brussels B-1050, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mondher","family":"El Jaziri","sequence":"additional","affiliation":[{"name":"Laboratory of Plant Biotechnology, Faculty of Sciences, Universit\u00e9 Libre de Bruxelles,  12 rue des Professeurs Jeener et Brachet, Gosselies B-6041, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Duez","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy, Bromatology and Human Nutrition, Faculty of Pharmacy, Universit\u00e9 Libre de Bruxelles, CP 205\/9, Boulevard du Triomphe, Brussels B-1050, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,6,14]]},"reference":[{"key":"ref_1","unstructured":"Schaechter, M. (2009). Encyclopedia of Microbiology, Elsevier Inc. [3rd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.baae.2005.07.003","article-title":"Oak gall wasp communities: Evolution and ecology","volume":"6","author":"Hayward","year":"2005","journal-title":"Basic Appl. Ecol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1000179","DOI":"10.1371\/journal.pbio.1000179","article-title":"Host niches and defensive extended phenotypes structure parasitoid wasp communities","volume":"7","author":"Bailey","year":"2009","journal-title":"PLoS Biol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-phyto-080508-081803","article-title":"Recent evolution of bacterial pathogens: The gall-forming Plantoea Agglomerans case","volume":"47","author":"Barash","year":"2009","journal-title":"Annu. Rev. Phytopathol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-phyto-072910-095217","article-title":"Successful bacterial coup d\u2019\u00c9tat: How Rhodococcus fascians redirects plant development","volume":"49","author":"Stes","year":"2011","journal-title":"Annu. Rev. Phytopathol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jep.2004.09.016","article-title":"Inhibition of fowlpox virus by an aqueous acetone extract from galls of Guiera senegalensis J.F. Gmel (Combretaceae)","volume":"96","author":"Lamien","year":"2005","journal-title":"J. Ethnopharmacol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.cbi.2007.10.002","article-title":"Quercus infectoria galls possess antioxidant activity and abrogates oxidative stress-induced functional alterations in murine macrophages","volume":"171","author":"Kaur","year":"2008","journal-title":"Chem. Biol. Interact"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jep.2005.04.036","article-title":"Wisteria floribunda gall extract inhibits cell migration in mouse B16F1 melanoma cells by regulating CD44 expression and GTP-RhoA activity","volume":"102","author":"Heo","year":"2005","journal-title":"J. Ethnopharmacol"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1128\/AEM.71.3.1169-1177.2005","article-title":"Biosynthesis of auxin by the Gram-positive phytopathogen Rhodococcus fascians is controlled by compounds specific to infected plants","volume":"71","author":"Vandeputte","year":"2005","journal-title":"Appl. Environ. Microbiol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1094\/MPMI-23-9-1164","article-title":"Rhodococcus fascians impacts plant development through the dynamic fas-mediated production of a cytokinin mix","volume":"23","author":"Pertry","year":"2010","journal-title":"Mol. Plant Microbe Interact"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1364-3703.2006.00322.x","article-title":"The phytopathogen Rhodococcus fascians breaks apical dominance and activates axillary meristems by inducing plant genes involved in hormone metabolism","volume":"7","author":"Depuydt","year":"2006","journal-title":"Mol. Plant Pathol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1104\/pp.108.131805","article-title":"An integrated genomics approach to define niche establishment by Rhodococcus fascians","volume":"149","author":"Depuydt","year":"2009","journal-title":"Plant Physiol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s004250050076","article-title":"Patterns of phenolic compounds in leafy galls of tobacco","volume":"201","author":"Vereecke","year":"1997","journal-title":"Planta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jbiotec.2011.06.002","article-title":"Marine actinomycetes as an emerging resource for the drug development pipelines","volume":"158","author":"Zotchev","year":"2012","journal-title":"J. Biotechnol"},{"key":"ref_15","first-page":"373","article-title":"Biologically active secondary metabolites from Actinomycetes","volume":"7","author":"Solecka","year":"2012","journal-title":"Cent. Eur. J. Biol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3109\/07388551.2011.630647","article-title":"Medicinal halophytes: Potent source of health promoting biomolecules with medical, nutraceutical and food applications","volume":"32","author":"Ksouri","year":"2012","journal-title":"Crit. Rev. Biotechnol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2217\/fmb.12.68","article-title":"Plant-derived antimicrobial compounds: Alternatives to antibiotics","volume":"7","author":"Savoia","year":"2012","journal-title":"Future Microbiol"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s00284-010-9685-3","article-title":"The diversity and anti-microbial activity of endophytic Actinomycetes isolated from medicinal plants in Panxi plateau, China","volume":"62","author":"Zhao","year":"2011","journal-title":"Curr. Microbiol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1439-0434.2012.01953.x","article-title":"In vitro antioxidant and anti-inflammatory activities of extracts from Nicotiana tabacum L. (Solanaceae) leafy galls induced by Rhodococcus fascians","volume":"160","author":"Nacoulma","year":"2012","journal-title":"J. Phytopathol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1365-313X.2012.04902.x","article-title":"High-resolution plant metabolomics: From mass spectral features to metabolites and from whole-cell analysis to subcellular metabolite distributions","volume":"70","author":"Kueger","year":"2012","journal-title":"Plant J"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1055\/s-0031-1298496","article-title":"Metabolic Fingerprinting by 1HNMR for discrimination of the two species used as Radix Bupleuri","volume":"78","author":"Qin","year":"2012","journal-title":"Planta Med"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s11306-008-0154-y","article-title":"Application of NMR based metabolomics for mapping metabolite variation in European wheat","volume":"5","author":"Graham","year":"2009","journal-title":"Metabolomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.chroma.2003.08.027","article-title":"Optimization of headspace solid phase microextraction for gas chromatography\/mass spectrometry analysis of widely different volatility and polarity terpenoids in olibanum","volume":"1018","author":"Hamm","year":"2003","journal-title":"J. Chromatogr. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1471-2229-11-76","article-title":"Gene expression profile analysis of tobacco leaf trichomes","volume":"11","author":"Cui","year":"2011","journal-title":"BMC Plant Biol"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.plaphy.2011.11.006","article-title":"Role of pathogen-induced volatiles in the Nicotiana tabacum-Golovinomyces cichoracearum interaction","volume":"52","author":"Quaglia","year":"2012","journal-title":"Plant Physiol. Biochem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00425-003-1039-y","article-title":"Differential volatile emissions and salicylic acid levels from tobacco plants in response to different strains of Pseudomonas syringae","volume":"217","author":"Huang","year":"2003","journal-title":"Planta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1105\/tpc.010231","article-title":"A diterpene as an endogenous signal for the activation of defense responses to infection with tobacco mosaic virus and wounding in tobacco","volume":"15","author":"Seo","year":"2003","journal-title":"Plant Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.pbi.2009.05.011","article-title":"Plants under attack: Systemic signals in defense","volume":"12","author":"Shah","year":"2009","journal-title":"Curr. Opin. Plant Biol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1021\/ac0713510","article-title":"Visualization of GC\/TOF-MS-based metabolomics data for identification of biochemically interesting compounds using OPLS class models","volume":"80","author":"Wiklund","year":"2008","journal-title":"Anal. Chem"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1021\/np050535b","article-title":"NMR metabolomics to revisit the tobacco mosaic virus infection in Nicotiana tabacum leaves","volume":"69","author":"Choi","year":"2006","journal-title":"J. Nat. Prod"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1016\/j.phytochem.2007.07.010","article-title":"The future of metabolic phytochemistry: Larger numbers of metabolites, higher resolution, greater understanding","volume":"68","author":"Fernie","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.phytochem.2009.09.018","article-title":"Metabolic profiles of sunflower genotypes with contrasting response to Sclerotinia sclerotiorum infection","volume":"71","author":"Peluffo","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1093\/jxb\/erm298","article-title":"Plant physiology meets phytopathology: Plant primary metabolism and plant\u2013pathogen interactions","volume":"58","author":"Berger","year":"2007","journal-title":"J. Exp. Bot"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1023\/A:1023521626899","article-title":"Screening for differential gene expression in Atropa belladonna leafy gall induced following Rhodococcus fascians infection","volume":"109","author":"Nouar","year":"2003","journal-title":"Eur. J. Plant Pathol"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1364-3703.2007.00385.x","article-title":"The tobacco Ntann12 gene, encoding an annexin, is induced upon Rhodococcus fascians infection and during leafy gall development","volume":"8","author":"Vandeputte","year":"2007","journal-title":"Mol. Plant Pathol"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/35081178","article-title":"Natural products and plant disease resistance","volume":"411","author":"Dixon","year":"2001","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e18127","DOI":"10.1371\/journal.pone.0018127","article-title":"Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria","volume":"6","author":"Fiamegos","year":"2011","journal-title":"PLoS One"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1055\/s-0030-1250478","article-title":"Bioactive natural, biocatalytic, and semisynthetic tobacco cembranoids","volume":"77","author":"Baraka","year":"2011","journal-title":"Planta Med"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/j.1462-2920.2011.02424.x","article-title":"Virulence quenching with a prenylated isoflavanone renders the Malagasy legume Dalbergia pervillei resistant to Rhodococcus fascians","volume":"13","author":"Rajaonson","year":"2011","journal-title":"Environ. Microbiol"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1016\/j.yexcr.2008.06.010","article-title":"Videomicroscopic extraction of specific information on cell proliferation and migration in vitro","volume":"314","author":"Debeir","year":"2008","journal-title":"Exp. Cell Res"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bury, M., and Girault, A (2013). Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity. Cell Death Dis, 4.","DOI":"10.1038\/cddis.2013.85"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/6\/12533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:47:21Z","timestamp":1760219241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/14\/6\/12533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,14]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,6]]}},"alternative-id":["ijms140612533"],"URL":"https:\/\/doi.org\/10.3390\/ijms140612533","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,14]]}}}