Abstract
To date, endophytic actinomycetes have been well-documented as great producers of novel antibiotics and important pharmaceutical leads. The present study aimed to evaluate potent bioactivities of metabolites synthesized by the strain LCP18 residing in the Vietnamese medicinal plant Litsea cubeba (Lour.) Pers towards human pathogenic bacteria and human cancer cell lines. Endophytic actinomycete strain LCP18 showed considerable inhibition against seven bacterial pathogens and three human tumor cell lines and was identified as species Streptomyces variabilis. Strain S. variabilis LCP18 was phenotypically resistant to fosfomycin, trimethoprim-sulfamethoxazole, dalacin, cefoxitin, rifampicin, and fusidic acid and harbored the two antibiotic biosynthetic genes such as PKS-II and NRPS. Further purification and structural elucidation of metabolites from the LCP18 extract revealed five plant-derived bioactive compounds including isopcrunetin, genistein, daidzein, syringic acid, and daucosterol. Among those, isoprunetin, genistein, and daidzein exhibited antibacterial activity against Salmonella typhimurium ATCC 14,028 and methicillin-resistant Staphylococcus epidermidis ATCC 35,984 with the MIC values ranging from 16 to 128 µg/ml. These plant-derived compounds also exhibited cytotoxic effects against human lung cancer cell line A549 with IC50 values of less than 46 μM. These findings indicated that endophytic S. variabilis LCP18 can be an alternative producer of plant-derived compounds which significantly show potential applications in combating bacterial infections and inhibition against lung cancer cell lines.
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Das R, Romi W, Das R, Sharma HK, Thakur D (2018) Antimicrobial potentiality of actinobacteria isolated from two microbiologically unexplored forest ecosystems of Northeast India. BMC Microbiol 18(1):71. https://doi.org/10.1186/s12866-018-1215-7
Govindasamy V, Franco CMM, Gupta VVSR (2013) Endophytic Actinobacteria: diversity and ecology. Advances in Endophytic Research. Springer India. https://doi.org/10.1007/978-81-322-1575-2_2
Berdy J (2005) Bioactive microbial metabolites. J Antibiot 58(1):1–26. https://doi.org/10.1038/ja.2005.1
Christina A, Christapher V, Bhore SJ (2013) Endophytic bacteria as a source of novel antibiotics: an overview. Pharmacogn Rev 7(13):11. https://doi.org/10.4103/0973-7847.112833
Guo B, Wang Y, Sun X, Tang K (2008) Bioactive natural products from endophytes: a review. Appl Biochem Microbiol 44(2):136–142. https://doi.org/10.1134/S0003683808020026
Sadrati N, Daoud H, Zerroug A, Dahamna S, Bouharati S (2013) Screening of antimicrobial and antioxidant secondary metabolites from endophytic fungi isolated from wheat (Triticum durum). J Plant Prot Res 53(2):128–136. https://doi.org/10.2478/jppr-2013-0019
Jose PA, Jha B (2016) New dimensions of research on actinomycetes: quest for next generation antibiotics. Front Microbiol 7:1295–1295. https://doi.org/10.3389/fmicb.2016.01295
Salam N, Khieu T-N, Liu M-J, Vu T-T, Chu-Ky S, Quach N-T, Phi Q-T, Rao N, Prabhu M, Fontana A (2017) Endophytic actinobacteria associated with Dracaena cochinchinensis Lour.: isolation, diversity, and their cytotoxic activities. BioMed Res Intern 2017. https://doi.org/10.1155/2017/1308563
Vu THN, Nguyen QH, Dinh TML, Quach NT, Khieu TN, Hoang H, Son C-K, Vu TT, Chu HH, Lee J (2020) Endophytic actinomycetes associated with Cinnamomum cassia Presl in Hoa Binh province, Vietnam: Distribution, antimicrobial activity and genetic features. J Gen Appl Microbiol 66:24–31. https://doi.org/10.2323/jgam.2019.04.004
Subramani R, Aalbersberg W (2013) Culturable rare Actinomycetes: diversity, isolation and marine natural product discovery. Appl Microbiol Biotechnol 97(21):9291–9321. https://doi.org/10.1007/s00253-013-5229-7
Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70(3):461–477. https://doi.org/10.1021/np068054v
Qin S, Li J, Chen H-H, Zhao G-Z, Zhu W-Y, Jiang C-L, Xu L-H, Li W-J (2009) Isolation, diversity, and antimicrobial activity of rare actinobacteria from medicinal plants of tropical rain forests in Xishuangbanna. China. Appl Environ Microbiol 75(19):6176–6186. https://doi.org/10.1128/AEM.01034-09
Kawahara T, Izumikawa M, Otoguro M, Yamamura H, Hayakawa M, Takagi M, Shin-ya K (2012) JBIR-94 and JBIR-125, antioxidative phenolic compounds from Streptomyces sp. R56–07. J Nat Prod 75(1):107–110. https://doi.org/10.1021/np200734p
Kekuda P, Onkarappa R, Jayanna N (2015) Characterization and antibacterial activity of a glycoside antibiotic from Streptomyces variabilis PO-178. STAR 3(4):116–121. https://doi.org/10.4314/star.v3i4.17
Passari AK, Mishra VK, Saikia R, Gupta VK, Singh BP (2015) Isolation, abundance and phylogenetic affiliation of endophytic actinomycetes associated with medicinal plants and screening for their in vitro antimicrobial biosynthetic potential. Front Microbiol 6:273. https://doi.org/10.3389/fmicb.2015.00273
McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM (2017) Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther 31(1):63–75. https://doi.org/10.1007/s10557-016-6711-0
Sasaki T, Igarashi Y, Saito N, Furumai T (2001) Cedarmycins A and B, new antimicrobial antibiotics from Streptomyces sp. TP-A0456. J Antibiot (Tokyo) 54(7):567–572. https://doi.org/10.7164/antibiotics.54.567
Lu C, Shen Y (2007) A novel ansamycin, naphthomycin K from Streptomyces sp. J Antibiot 60(10):649–653. https://doi.org/10.1038/ja.2007.84
Kong D-G, Zhao Y, Li G-H, Chen B-J, Wang X-N, Zhou H-L, Lou H-X, Ren D-M, Shen T (2015) The genus Litsea in traditional Chinese medicine: an ethnomedical, phytochemical and pharmacological review. J Ethnopharmacol 164:256–264. https://doi.org/10.1016/j.jep.2015.02.020
Wang H, Liu Y (2010) Chemical composition and antibacterial activity of essential oils from different parts of Litsea cubeba. Chem Biodivers 7(1):229–235. https://doi.org/10.1002/cbdv.200800349
Nguyen QH, Nguyen HV, Vu TH-N, Chu-Ky S, Vu TT, Hoang H, Quach NT, Bui TL, Chu HH, Khieu TN, Sarter S, Li W-J, Phi Q-T (2019) Characterization of endophytic Streptomyces griseorubens MPT42 and assessment of antimicrobial synergistic interactions of its extract and essential oil from host plant Litsea cubeba. Antibiotics 8(4):197. https://doi.org/10.3390/antibiotics8040197
Jin L, Zhao Y, Song W, Duan L, Jiang S, Wang X, Zhao J, Xiang W (2019) Streptomyces inhibens sp. nov., a novel actinomycete isolated from rhizosphere soil of wheat (Triticum aestivum L.). Int J Syst Evol Microb 69(3):688–695. https://doi.org/10.1099/ijsem.0.003204
Vu HT, Nguyen DT, Nguyen HQ, Chu HH, Chu SK, Chau MV, Phi QT (2018) Antimicrobial and cytotoxic properties of bioactive metabolites produced by Streptomyces cavourensis YBQ59 isolated from Cinnamomum cassia Prels in Yen Bai Province of Vietnam. Curr Microbiol 75(10):1247–1255. https://doi.org/10.1007/s00284-018-1517-x
CLSI (2017) Performance standards for antimicrobial susceptibility testing. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute 27th ed
Singh V, Haque S, Kumari V, El-Enshasy HA, Mishra BN, Somvanshi P, Tripathi CKM (2019) Isolation, purification, and characterization of heparinase from Streptomyces variabilis MTCC 12266. Sci Rep 9(1):6482. https://doi.org/10.1038/s41598-019-42740-7
Jiang S, Li XL, Zhang L, Sun W, Dai S, Xie L, Liu Y, Lee KJ (2008) Culturable actinobacteria isolated from marine sponge Iotrochota sp. Mar Biol 153:945–952
Kinkel LL, Schlatter DC, Xiao K, Baines AD (2014) Sympatric inhibition and niche differentiation suggest alternative coevolutionary trajectories among Streptomycetes. ISME J 8(2):249–256. https://doi.org/10.1038/ismej.2013.175
Dholakiya RN, Kumar R, Mishra A, Mody KH, Jha B (2017) Antibacterial and antioxidant activities of novel actinobacteria strain isolated from Gulf of Khambhat. Gujarat Front Microbiol 8:2420. https://doi.org/10.3389/fmicb.2017.02420
Tan LT-H, Ser H-L, Yin W-F, Chan K-G, Lee L-H, Goh B-H (2015) Investigation of antioxidative and anticancer potentials of Streptomyces sp. MUM256 isolated from Malaysia mangrove soil. Front Microbiol 6 (1316). https://doi.org/10.3389/fmicb.2015.01316
Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M (2007) Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28(6):622–629. https://doi.org/10.1002/humu.20495
Goh BH, Chan CK, Kamarudin MN, Abdul Kadir H (2014) Swietenia macrophylla King induces mitochondrial-mediated apoptosis through p53 upregulation in HCT116 colorectal carcinoma cells. J Ethnopharmacol 153(2):375–385. https://doi.org/10.1016/j.jep.2014.02.036
Ndjateu FST, Tsafack RBN, Nganou BK, Awouafack MD, Wabo HK, Tene M, Tane P, Eloff JN (2014) Antimicrobial and antioxidant activities of extracts and ten compounds from three Cameroonian medicinal plants: Dissotis perkinsiae (Melastomaceae), Adenocarpus mannii (Fabaceae) and Barteria fistulosa (Passifloraceae). S Afr J Bot 91:37–42. https://doi.org/10.1016/j.sajb.2013.11.009
Feng S, Hao J, Xu Z, Chen T, Qiu SX (2012) Polyprenylated isoflavanone and isoflavonoids from Ormosia henryi and their cytotoxicity and anti-oxidation activity. Fitoterapia 83(1):161–165. https://doi.org/10.1016/j.fitote.2011.10.007
Sail V, Hadden MK (2012) Chapter eighteen-notch Pathway modulators as anticancer chemotherapeutics. In: Desai MC (ed) Annual reports in medicinal chemistry, vol 47. Academic Press, pp 267–280. https://doi.org/10.1016/B978-0-12-396492-2.00018-7
Danciu C, Antal DS, Ardelean F, Chiş AR, Şoica C, Andrica F, Dehelean C (2017) New insights regarding the potential health benefits of isoflavones. Flavonoids-from biosynthesis to human health Rijeka, Croatia: Intech:257–286. https://doi.org/10.5772/67896
Yang Y, Zang A, Jia Y, Shang Y, Zhang Z, Ge K, Zhang J, Fan W, Wang B (2016) Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling. Oncol Lett 12(3):2189–2193. https://doi.org/10.3892/ol.2016.4817
Hong H, Landauer MR, Foriska MA, Ledney GD (2006) Antibacterial activity of the soy isoflavone genistein. J Basic Microbiol 46(4):329–335. https://doi.org/10.1002/jobm.200510073
Srinivasulu C, Ramgopal M, Ramanjaneyulu G, Anuradha CM, Suresh Kumar C (2018) Syringic acid (SA)-a review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed Pharmacother 108:547–557. https://doi.org/10.1016/j.biopha.2018.09.069
Ha SJ, Lee J, Park J, Kim YH, Lee NH, Kim YE, Song KM, Chang PS, Jeong CH, Jung SK (2018) Syringic acid prevents skin carcinogenesis via regulation of NoX and EGFR signaling. Biochem Pharmacol 154:435–445. https://doi.org/10.1016/j.bcp.2018.06.007
Shi C, Sun Y, Zheng Z, Zhang X, Song K, Jia Z, Chen Y, Yang M, Liu X, Dong R, Xia X (2016) Antimicrobial activity of syringic acid against Cronobacter sakazakii and its effect on cell membrane. Food Chem 197(Pt A):100–106. https://doi.org/10.1016/j.foodchem.2015.10.100
Antibacterial activities of plant-derived compounds and essential oils toward Cronobacter sakazakii and Cronobacter malonaticus (2014). FOODBORNE PATHOG DIS 11 (10):795–797. https://doi.org/10.1089/fpd.2014.1737
Campos FM, Couto JA, Figueiredo AR, Tóth IV, Rangel AO, Hogg TA (2009) Cell membrane damage induced by phenolic acids on wine lactic acid bacteria. Int J Food Microbiol 135(2):144–151. https://doi.org/10.1016/j.ijfoodmicro.2009.07.031
Calderón-Oliver M, Ponce-Alquicira E (2018) Chapter 7 - Fruits: A source of polyphenols and health benefits. In: Grumezescu AM, Holban AM (eds) Natural and artificial flavoring agents and food dyes. Academic Press, pp 189–228. https://doi.org/10.1016/B978-0-12-811518-3.00007-7
Choi EJ, Kim GH (2014) The antioxidant activity of daidzein metabolites, O-desmethylangolensin and equol, in HepG2 cells. Mol Med Rep 9(1):328–332. https://doi.org/10.3892/mmr.2013.1752
Liu N, Wang H, Liu M, Gu Q, Zheng W, Huang Y (2009) Streptomyces alni sp. nov., a daidzein-producing endophyte isolated from a root of Alnus nepalensis D. Don. Int J Syst Evol 59(2):254–258. https://doi.org/10.1099/ijs.0.65769-0
Yang Y, Yang X, Zhang Y, Zhou H, Zhang J, Xu L, Ding Z (2013) A new daidzein derivative from endophytic Streptomyces sp. YIM 65408. Nat Prod Res 27(19):1727–1731. https://doi.org/10.1080/14786419.2012.750317
Gao P, Huang X, Liao T, Li G, Yu X, You Y, Huang Y (2019) Daucosterol induces autophagic-dependent apoptosis in prostate cancer via JNK activation. Biosci Trends 13(2):160–167. https://doi.org/10.5582/bst.2018.01293
Rajavel T, Mohankumar R, Archunan G, Ruckmani K, Devi KP (2017) Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells. Sci Rep 7(1):3418–3418. https://doi.org/10.1038/s41598-017-03511-4
Acknowledgements
We are grateful with the support of VAST – Culture Collection of Microorganisms, Institute of Biotechnology, Vietnam Academy of Science and Technology (http://www.vccm.vast.vn) and LMI DRISA, University of Science and Technology of Hanoi (USTH), VAST for implementing this project.
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This study was financially supported by Vietnam Academy of Science and Technology (VAST) under grant number ĐLTE00.03/21–22.
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NTQ, QHN, THNV, TTHL, TTTT, TDN, VTN, and HHC: experimental procedures, data preparation, and interpretation. NTQ, QHN, and QTP: writing the manuscript. VTD, TTD, and XCN: reviewing the manuscript. NTQ, QTP, and THNV: manuscript preparation and funding acquisition. All authors read and approved the final manuscript.
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Quach, N.T., Nguyen, Q.H., Vu, T.H.N. et al. Plant-derived bioactive compounds produced by Streptomyces variabilis LCP18 associated with Litsea cubeba (Lour.) Pers as potential target to combat human pathogenic bacteria and human cancer cell lines. Braz J Microbiol 52, 1215–1224 (2021). https://doi.org/10.1007/s42770-021-00510-6
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DOI: https://doi.org/10.1007/s42770-021-00510-6