{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:46:17Z","timestamp":1789681577228,"version":"4.0.1"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T00:00:00Z","timestamp":1515974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish National Science Centre","award":["2013\/11\/D\/NZ7\/01613"],"award-info":[{"award-number":["2013\/11\/D\/NZ7\/01613"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: On account of emergence of multi- and extensively drug-resistant Mycobacterium tuberculosis (Mtb) strains, combinations of drugs with natural compounds were tested to search for antibiotic activity enhancers. In this work we studied terpenes (\u03b1-pinene, bisabolol, \u03b2-elemene, (R)-limonene, (S)-limonene, myrcene, sabinene), which are the main constituents of essential oil obtained from Mutellina purpurea L., a plant with described antitubercular activity, to investigate their interactions with antibiotics against reference Mtb strains and multidrug-resistant clinical isolates. Methods: The serial dilution method was used to evaluate the minimal inhibitory concentration (MIC) of tested compounds, while the fractional inhibitory concentration index (FICI) was calculated for characterization of interactions. Moreover, IC50 values of tested compounds were determined using monkey kidney epithelial cell line (GMK). Results: The combinations of all studied terpenes with ethambutol or rifampicin resulted in a synergistic interaction. Bisabolol and (R)-limonene decreased the MIC for rifampicin at least two-fold for all tested strains, however no synergistic action was observed against virulent strains. The tested terpenes showed slight (bisabolol) or no cytotoxic effect against normal eukaryotic cells in vitro. Conclusions: The obtained enhanced activity (FICI &lt; 0.5) of ethambutol and rifampicin against H37Ra strain under the influence of the studied terpenes may be correlated to the capability of essential oil constituents to modify bacterial resistance mechanisms in general. The observed differences in avirulent and virulent bacteria susceptibility to terpenes tested separately and in combinations with antibiotics can be correlated with the differences in the cell wall structure between H37Ra mutant and all virulent strains.<\/jats:p>","DOI":"10.3390\/molecules23010176","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T12:30:36Z","timestamp":1516019436000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The Effect of Combining Natural Terpenes and Antituberculous Agents against Reference and Clinical Mycobacterium tuberculosis Strains"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-0329","authenticated-orcid":false,"given":"Elwira","family":"Sieniawska","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy with Medicinal Plant Unit, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Sawicki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Swatko-Ossor","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-9242","authenticated-orcid":false,"given":"Agnieszka","family":"Napiorkowska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-1309","authenticated-orcid":false,"given":"Agata","family":"Przekora","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazyna","family":"Ginalska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Swatko-Ossor","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Augustynowicz-Kopec","sequence":"additional","affiliation":[{"name":"Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2016). Global Tuberculosis Report, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1099\/jmm.0.014837-0","article-title":"In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis","volume":"59","author":"Ge","year":"2010","journal-title":"J. Med. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jep.2015.12.008","article-title":"Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii","volume":"178","author":"Knezevic","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.phymed.2007.01.005","article-title":"Antibacterial effect of some essential oils administered alone or in combination with norfloxacin","volume":"14","author":"Rosato","year":"2007","journal-title":"Phytomedecine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejps.2011.04.012","article-title":"Transformation of cinnamic acid from trans- to cis-form raises a notable bactericidal and synergistic activity against multiple-drug resistant Mycobacterium tuberculosis","volume":"43","author":"Chen","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-695X.1998.tb01161.x","article-title":"Synergistic activities of antituberculous drugs with cerulenin and trans-cinnami cacid against Mycobacterium tuberculosis","volume":"21","author":"Rastogi","year":"1998","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phymed.2011.06.033","article-title":"Antifungal activity of Coriandrum sativum essential oil, its mode of action against Candida species and potential synergism with amphotericin B","volume":"19","author":"Silva","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6300","DOI":"10.1021\/jf070094x","article-title":"Interaction of four monoterpenes contained in essential oils with model membranes: Implications for their antibacterial activity","volume":"55","author":"Cristani","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","first-page":"795435","article-title":"Antibacterial effects and mode of action of selected essential oils components against Escherichia coli and Staphylococcus aureus","volume":"2015","author":"Borges","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.3390\/ph6121451","article-title":"Effect of essential oils on pathogenic bacteria","volume":"6","author":"Nazzaro","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1128\/AAC.49.6.2474-2478.2005","article-title":"Mechanisms of antibacterial action of three monoterpenes","volume":"49","author":"Trombetta","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","first-page":"3","article-title":"Essential oils in food preservation: Mode of action, synergies, and interactions with food matrix components","volume":"25","author":"Hyldgaard","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3109\/1040841X.2013.763219","article-title":"Synergy between essential oil components and antibiotics: A review","volume":"40","author":"Langeveld","year":"2014","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.2174\/092986710792231996","article-title":"In vitro synergistic antibacterial action of certain combinations of gentamicin and essential oils","volume":"17","author":"Rosato","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.apjtb.2015.09.024","article-title":"Evaluation of antibacterial activity and synergistic effect between antibiotic and the essential oils of some medicinal plants","volume":"6","author":"Moussaoui","year":"2016","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.biosystems.2008.05.038","article-title":"Classification of antituberculosis herbs for remedial purposes by using fuzzy sets","volume":"94","author":"Dudek","year":"2008","journal-title":"BioSystems"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Baser, K.H.C., and Buchbauer, G. (2015). Handbook of Essential Oils: Science, Technology, and Applications, CRC Press.","DOI":"10.1201\/b19393"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1023\/A:1005547131427","article-title":"Occurrence and correlations of monoterpene hydrocarbon enantiomers in pinus sylvestris and picea abies","volume":"26","author":"Sjodin","year":"2000","journal-title":"J. Chem. Ecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.indcrop.2017.08.057","article-title":"Antimicrobial and antioxidant activity of Juniper galbuli essential oil constituents eluted at different times","volume":"109","author":"Zheljazkov","year":"2017","journal-title":"Ind. Crops Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/0972060X.2014.890075","article-title":"Chemical composition of the essential oil of Ssatureja myrtifolia (Boiss. & Hohen.) from Lebanon","volume":"18","author":"Zebib","year":"2015","journal-title":"J. Essent. Oil-Bear. Plants"},{"key":"ref_21","unstructured":"Healthcare, T. (2007). PDR for Herbal Medicine, Medical Economics Company."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s11101-013-9331-3","article-title":"The evolution of foliar terpene diversity in myrtaceae","volume":"13","author":"Padovan","year":"2014","journal-title":"Phytochem. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.apjtb.2017.01.004","article-title":"Chemical characterization of essential oil from the leaves of Callistemon viminalis (D.R.) and Melaleuca leucadendron (Linn.)","volume":"4","author":"Fall","year":"2017","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11746-009-1483-3","article-title":"Review of the application and pharmacological properties of alpha-bisabolol and alpha-bisabolol-rich oils","volume":"87","author":"Kamatou","year":"2010","journal-title":"J. Am. Oil Chem. Soc. (JAOCS)"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.5897\/AJPP11.670","article-title":"A review of medicinal plant species with elemene in China","volume":"6","author":"Wang","year":"2012","journal-title":"Afr. J. Pharm. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Borek, T.T., Hochrein, J.M., and Irwin, A.N. (2003). Composition of the Essential Oils from Rocky Mountain Juniper (Juniperus scopulorum), Big Sagebrush (Artemisia tridentata), and White Sage (Salvia Apiana), Sandia National Laboratories.","DOI":"10.2172\/918273"},{"key":"ref_27","first-page":"135","article-title":"Chemical composition of essential oil of nutmeg (Mmyristica fragrans Hout) accessions","volume":"13","author":"Maya","year":"2004","journal-title":"J. Species Aromat. Crops"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jfoodeng.2005.11.010","article-title":"Extraction of the essential oil of thyme and black pepper by superheated steam","volume":"78","author":"Rouatbi","year":"2007","journal-title":"J. Food Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.indcrop.2016.08.001","article-title":"Carrot seed essential oil\u2014Source of carotol and cytotoxicity study","volume":"92","author":"Sieniawska","year":"2016","journal-title":"Ind. Crops Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1159\/000439351","article-title":"Morphological changes in the overall Mycobacterium tuberculosis H37Ra cell shape and cytoplasm homogeneity due to Mutellina purpurea L. Essential oil and its main constituents","volume":"24","author":"Sieniawska","year":"2015","journal-title":"Med. Princ. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000454680","article-title":"Natural terpenes influence the activity of antibiotics against isolated Mycobacterium tuberculosis","volume":"26","author":"Sieniawska","year":"2017","journal-title":"Med. Princ. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1128\/JCM.40.10.3851-3853.2002","article-title":"Use of spoligotyping for accurate classification of recurrent tuberculosis","volume":"40","author":"Warren","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1590\/S0044-59672007000200015","article-title":"Cytotoxic evaluation of essential oil from Zanthoxylum rhoifolium Lam. Leaves","volume":"37","author":"Figueiredo","year":"2007","journal-title":"Acta Amazon."},{"key":"ref_34","unstructured":"Huang, L. (2006). Synthesis of (\u2212)-Beta-elemene, (\u2212)-Beta-elemenal, (\u2212)-Beta-elemenol, (\u2212)-Beta-elemene Fluoride and Their Analogues, Intermediates and Composition and Uses Thereof. (WO 2006016912 A2)."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ijmyco.2015.05.004","article-title":"Current perspectives in drug discovery against tuberculosis from natural products","volume":"4","author":"Nguta","year":"2015","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Andrade-Ochoa, S., Nev\u00e1rez-Moorill\u00f3n, G.V., S\u00e1nchez-Torres, L.E., Villanueva-Garc\u00eda, M., S\u00e1nchez-Ram\u00edrez, B.E., Rodr\u00edguez-Valdez, L.M., and Rivera-Chavira, B.E. (2015). Quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0858-2"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1104\/pp.117.3.901","article-title":"Biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway. I. Demonstration of enzyme activities and their changes with development","volume":"117","author":"Bouwmeester","year":"1998","journal-title":"Plant Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7750","DOI":"10.3390\/molecules15117750","article-title":"Farnesol, a potential efflux pump inhibitor in Mycobacterium smegmatis","volume":"15","author":"Jin","year":"2010","journal-title":"Molecules"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sawicki, R., Sieniawska, E., Swatko-Ossor, M., Golus, J., and Ginalska, G. (2017). The frequently occurring components of essential oils beta-elemene and R-limonene alter expression of dprE1 and clgr genes of mycobacterium tuberculosis h37ra. Food Chem. Toxicol., 145\u2013149.","DOI":"10.1016\/j.fct.2017.12.052"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2174\/1874285801408010006","article-title":"Essential oils, a new horizon in combating bacterial antibiotic resistance","volume":"8","author":"Yap","year":"2014","journal-title":"Open Microbiol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1128\/MMBR.00001-06","article-title":"The selective value of bacterial shape","volume":"70","author":"Young","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1128\/AAC.46.6.1914-1920.2002","article-title":"Mechanism of action of Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus determined by time-kill, lysis, leakage, and salt tolerance assays and electron microscopy","volume":"46","author":"Carson","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","first-page":"77","article-title":"Electron microscopic and biochemical investigations on the antibacterial effects of Australian tea tree oil against Staphylococcus aureus","volume":"5","author":"Reichling","year":"2002","journal-title":"Curr. Top. Phytochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"17773","DOI":"10.3390\/molecules191117773","article-title":"Antibacterial and antioxidant activity of essential oil terpenes against pathogenic and spoilage-forming bacteria and cell structure-activity relationships evaluated by sem microscopy","volume":"19","author":"Zengin","year":"2014","journal-title":"Molecules"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chom.2008.01.002","article-title":"Mutation in the transcriptional regulator phop contributes to avirulence of Mycobacterium tuberculosis H37Ra strain","volume":"3","author":"Lee","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1365-2958.2001.02500.x","article-title":"An essential role for phop in Mycobacterium tuberculosis virulence","volume":"41","author":"Perez","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.1365-2958.2006.05102.x","article-title":"The Mycobacterium tuberculosis phopr two-component system regulates genes essential for virulence and complex lipid biosynthesis","volume":"60","author":"Walters","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"29182","DOI":"10.1074\/jbc.M113.499905","article-title":"Unique n-terminal arm of Mycobacterium tuberculosis phop protein plays an unusual role in its regulatory function","volume":"288","author":"Das","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45197","DOI":"10.1074\/jbc.M111.307447","article-title":"Phosphorylation of Phop protein plays direct regulatory role in lipid biosynthesis of Mycobacterium tuberculosis","volume":"286","author":"Goyal","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1074\/jbc.C500388200","article-title":"The virulence-associated two component phop-phor system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis","volume":"281","author":"Asensio","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_51","first-page":"72","article-title":"Surface characteristics and adhesion of Escherichia coli and Staphylococcus epidermidis","volume":"71","author":"Gilbert","year":"1991","journal-title":"J. Appl. Bacteriol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1365-2672.2004.02181.x","article-title":"Adhesion of Staphylococcus aureus and Staphylococcus epidermidis to the episkin reconstructed epidermis model and to an inert stainless steel substrate","volume":"97","author":"Lerebour","year":"2004","journal-title":"J. Appl. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10295-007-0234-4","article-title":"Bacterial cell attachment, the beginning of a biofilm","volume":"34","author":"Palmer","year":"2007","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9135","DOI":"10.1021\/bi2012178","article-title":"Characterization of sulfolipids of Mycobacterium tuberculosis H37Rv by multiple-stage linear ion-trap high-resolution mass spectrometry with electrospray ionization reveals that the family of sulfolipid II predominates","volume":"50","author":"Rhoades","year":"2011","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1021\/jf980154m","article-title":"Characterization of the action of selected essential oil components on gram-negative bacteria","volume":"46","author":"Helander","year":"1998","journal-title":"J. Agric. Food Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"225103","DOI":"10.1088\/0957-4484\/18\/22\/225103","article-title":"Characterization of enhanced antibacterial effects of novel silver nanoparticles","volume":"18","author":"Shrivastava","year":"2007","journal-title":"Nanotechnology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1128\/aem.59.11.3605-3617.1993","article-title":"Phospholipid fatty acid comcosition, biomass, and activity of microbial communities from two soil types experimentally exposed to different heavy metals","volume":"199","author":"Frostegard","year":"1993","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13838","DOI":"10.1021\/jp503910r","article-title":"Effect of methyl-branched fatty acids on the structure of lipid bilayers","volume":"118","author":"Poger","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.tube.2012.01.005","article-title":"Synergistic effect of two combinations of antituberculous drugs against Mycobacterium tuberculosis","volume":"92","year":"2012","journal-title":"Tuberculosis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.phymed.2006.08.001","article-title":"Activity of 7-methyl-juglone in combination with antituberculous drugs against Mycobacterium tuberculosis","volume":"13","author":"Bapela","year":"2006","journal-title":"Phytomedicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1590\/0074-02760150454","article-title":"Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates","volume":"111","author":"Pereira","year":"2016","journal-title":"Mem\u00f3rias do Instituto Oswaldo Cruz"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ijantimicag.2012.11.011","article-title":"In vitro effect of three-drug combinations of antituberculous agents against multidrug-resistant Mycobacterium tuberculosis isolates","volume":"41","author":"Espasa","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijpharm.2015.11.042","article-title":"Synergistic interactions between doxycycline and terpenic components of essential oils encapsulated within lipid nanocapsules against gram negative bacteria","volume":"498","author":"Valcourt","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0092-8674(01)00286-0","article-title":"Structural mechanism for rifampicin inhibition of bacterial RNA polymerase","volume":"104","author":"Campbell","year":"2001","journal-title":"Cell"},{"key":"ref_65","unstructured":"Sieniawska, E., Sawicki, R., Swatko-Ossor, M., Ginalska, G., and Skalicka-Wozniak, K. (2017, January 10\u201313). Nigella damascena L. Essential oil\u2014A source of \u03b2-elemene for antimycobacterial testing. Proceedings of the 48th International Symposium on Essential Oils (ISEO2017), P\u00e9cs, Hungary."},{"key":"ref_66","first-page":"32","article-title":"Tuberculosis caused by xdr resistant Mycobacterium tuberculosis in Poland. Microbiological and molecular analysis","volume":"75","author":"Zwolska","year":"2007","journal-title":"Pol. Pulmonol. Allergol."},{"key":"ref_67","first-page":"151","article-title":"Progress in diagnostics and the molecular epidemiology of Mycobacterium tuberculosis","volume":"49","author":"Zwolska","year":"2010","journal-title":"Adv. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1471-2180-6-23","article-title":"Mycobacterium tuberculosis complex genetic diversity: Mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology","volume":"6","author":"Brudey","year":"2006","journal-title":"BMC Microbiol."},{"key":"ref_69","first-page":"536","article-title":"Primary and bcquired drug resistance of tuberculosis bacilli in Poland","volume":"67","author":"Zwolska","year":"1999","journal-title":"Pol. Pulmonol. Allergol."},{"key":"ref_70","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (1999). Methods for Determining Bactericidal Activity of Antimicrobial Agents. Approved Guideline, Clinical and Laboratory Standards Institute. CLSI Document M26-A."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.2147\/IJN.S140935","article-title":"Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors","volume":"12","author":"Kolmas","year":"2017","journal-title":"Int. J. Nanomed."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/1\/176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:51:21Z","timestamp":1760194281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/1\/176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,15]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1]]}},"alternative-id":["molecules23010176"],"URL":"https:\/\/doi.org\/10.3390\/molecules23010176","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,15]]}}}