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Molecular Biology Reports

, Volume 45, Issue 6, pp 2563–2570 | Cite as

Antimycobacterial activity of an anthracycline produced by an endophyte isolated from Amphipterygium adstringens

  • Miriam Trenado-Uribe
  • Mayra Silva-Miranda
  • José F. Rivero-Cruz
  • Karol Rodríguez-Peña
  • Clara I. Espitia-Pinzón
  • Romina Rodríguez-Sanoja
  • Sergio Sánchez
Original Article

Abstract

The search for new compounds effective against Mycobacterium tuberculosis is still a priority in medicine. The evaluation of microorganisms isolated from non-conventional locations offers an alternative to look for new compounds with antimicrobial activity. Endophytes have been successfully explored as source of bioactive compounds. In the present work we studied the nature and antimycobacterial activity of a compound produced by Streptomyces scabrisporus, an endophyte isolated from the medicinal plant Amphipterygium adstringens. The active compound was detected as the main secondary metabolite present in organic extracts of the streptomycete and identified by NMR spectroscopic data as steffimycin B (StefB). This anthracycline displayed a good activity against M. tuberculosis H37Rv ATCC 27294 strain, with MIC100 and SI values of 7.8 µg/mL and 6.42, respectively. When tested against the rifampin mono resistant M. tuberculosis Mtb-209 pathogen strain, a better activity was observed (MIC100 of 3.9 µg/mL), suggesting a different action mechanism of StefB from that of rifampin. Our results supported the endophyte Streptomyces scabrisporus as a good source of StefB for tuberculosis treatment, as this anthracycline displayed a strong bactericidal effect against M. tuberculosis, one of the oldest and more dangerous human pathogens causing human mortality.

Keywords

Anthracyclines Endophytes Streptomyces scabrisporus Steffimycin B Mycobacterium tuberculosis Amphipterygium adstringens Rifampin Tuberculosis 

Notes

Acknowledgements

This work was partially supported by the NUATEI program from Instituto de Investigaciones Biomédicas, and by PAPIIT (IN202216), DGAPA UNAM, México. We are indebted to Beatriz Ruiz-Villafán and Erika Segura Salinas for technical assistance in this work. The help of Marco A. Ortiz-Jiménez for strain preservation studies is recognized. We thank the support of CONACYT Project Number INFR-2017-01 279880, which allowed the acquisition of an HPLC masses.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interests.

Ethical statement

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

11033_2018_4424_MOESM1_ESM.pdf (426 kb)
Supplementary material 1 (PDF 426 KB)

References

  1. 1.
    Silva-Miranda M, Breiman A, Allain S, Deknuydt F, Altare F (2012) The tuberculous granuloma: an unsuccessful host defense mechanism providing a safety shelter for the bacteria? Clin Dev Immunol. 2012:139127CrossRefGoogle Scholar
  2. 2.
    Wong E, Cohen K, Bishai W (2013) Rising to the challenge: new therapies for tuberculosis. Trends Microbiol 21(9):493–501CrossRefGoogle Scholar
  3. 3.
    Kumar V, Patel S, Jain R (2016) New structural classes of antituberculosis agents. Med Res Rev 38(2):1–57Google Scholar
  4. 4.
    Demain AL, Sanchez S (2015) The need for new antibiotics. In: Sanchez S, Demain AL (eds) Antibiotics, current innovations and future trends. Caister Academic Press, North Folk, pp 65–82CrossRefGoogle Scholar
  5. 5.
    Genilloud O (2014) The re-emerging role of microbial natural products in antibiotic discovery. Antonie Van Leeuwenhoek 106:173–188CrossRefGoogle Scholar
  6. 6.
    Berdy J (2015) Microorganisms producing antibiotics. In: Sanchez S, Demain AL (Eds) Antibiotics, current innovations and future trends. Caister Academic Press, North Folk, pp 49–64CrossRefGoogle Scholar
  7. 7.
    Martínez-Klimova E, Rodríguez-Peña K, Sánchez S (2017) Endophytes as sources of antibiotics. Biochem Pharmacol 134:1–17CrossRefGoogle Scholar
  8. 8.
    Gutiérrez MP, González MN, Ramírez AM (2012) Compounds derived from endophytes: a review of phytochemistry and pharmacology. Curr Med Chem 19:2992–3030CrossRefGoogle Scholar
  9. 9.
    Rodriguez-Garcia A, Peixoto IT, Verde-Star MJ, De la Torre-Zavala S, Aviles-Arnaut H, Ruiz AL (2015) In vitro antimicrobial and antiproliferative activity of Amphipterygium adstringens. Evid Based Complementary Alternat Med 2015:175497CrossRefGoogle Scholar
  10. 10.
    Vazquez-Hernández M, Ceapa CD, Rodríguez-Luna SD, Rodríguez-Sanoja R, Sánchez S (2017) Draft genome sequence of Streptomyces scabrisporus NF3, endophyte isolated from Amphipterigium adstringens. Genome Announc 5:e00267–e00217PubMedPubMedCentralGoogle Scholar
  11. 11.
    Shirling EB, Gottlieb D (1966) Methods for characterization of Streptomyces species. Int J Syst Bacteriol 16:313–340CrossRefGoogle Scholar
  12. 12.
    Gohar YM, El-Naggar MY (2001) Induction of sporulation and antibacterial activity in the aerial mycelium negative mutants of Streptomyces nasri. Egypt J Biol3:23–35Google Scholar
  13. 13.
    Thomas KJ, Rice CV (2014) Revised model of calcium and magnesium binding to the bacterial cell wall. Biometals 27:1361–1370CrossRefGoogle Scholar
  14. 14.
    Alvarado C, García-Almendárez B, Martin S, Regalado C (2005) Anti-Listeria monocytogenes bacteriocin-like inhibitory substances from Enterococcus faecium UQ31 isolated from artisan mexican-style cheese. Curr Microbiol 51:110–115CrossRefGoogle Scholar
  15. 15.
    Linstrom PJ, Mallard WG (2015) NIST Chemistry WebBook, NIST Standard Reference Database. National Institute of Standards and Technology, Gaithersburg; 20899. http://webbook.nist.gov/chemistry/
  16. 16.
    Mossman T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRefGoogle Scholar
  17. 17.
    Collins L, Franzablau SG (1997) Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob Agents Chemother 41:1004–1009CrossRefGoogle Scholar
  18. 18.
    Enyinnaya F, Cruz P, Buttner MP, Cross C, Woodard DR (2017) Comparison of clinical and laboratory standards institute standards in antimicrobial susceptibility among the carbapenemase producing Enterobacteriaceae. Future Sci OA 3(4):FSO245CrossRefGoogle Scholar
  19. 19.
    Kelly RC, Schletter I, Koert JM, MacKellar FA, Wiley PF (1977) Structures of steffimycin and steffimycin B1. J Organic Chem 42:3591–3596CrossRefGoogle Scholar
  20. 20.
    Brodasky TF, Mizsak S, Hoffstetter JR (1985) Steffimycin C, a new member of the steffimycin anthracyclines. Isolation and structural characterization. J Antibiot (Tokyo) 38(7):849–855CrossRefGoogle Scholar
  21. 21.
    Brodasky TF, Reusser F (1974) Steffimycin B, a new member of the steffimycin family: isolation and characterization. J Antibiot 27:809–813CrossRefGoogle Scholar
  22. 22.
    Intaraudom C, Bunbamrung N, Dramae A, Danwisetkanjana K, Rachawee P, Pittayakhajonwut P (2015) Antimalarial and antimycobacterial agents from Streptomyces sp. BCC27095. Tetradehon Lett 56:6875–6877CrossRefGoogle Scholar
  23. 23.
    Lalitha P, Veena V, Vidhyapriya P, Lakshmi P, Krishna R, Sakthivel N (2016) Anticancer potential of pyrrole (1,2,a) pyrazine 1,4-dione, hexahydro 3-(2-methyl propyl) (PPDHMP) extracted from a new marine bacterium, Staphylococcus sp. strain MB30. Apoptosis 21(5), 566–577Google Scholar
  24. 24.
    Ser H-L, Palanisamy UD, Yin W-F, Abd Malek SN, Chan K-G, Goh B-H, Lee L-H (2015) Presence of antioxidative agent, Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro—in newly isolated Streptomyces mangrovisoli sp. nov. Front Microbi 6:854Google Scholar
  25. 25.
    Nirjanta D, Wahab F (2012) Antimicrobial properties of endophytic fungi isolated from medicinal plant Camellia sinesis. Int J Pharm Bio Sci. 3:P420–P427Google Scholar
  26. 26.
    Melo IS, Santos SN, Rosa LH, Parma MM, Silva LJ, Queiroz SCN, Pellizari VH (2014) Isolation and biological activities of an endophytic. Mortierella alpina strain from the Antarctic moss Schistidium antarctici. Extremophiles 18:15–23CrossRefGoogle Scholar
  27. 27.
    Li N, Zhang G, Yi FX, Zou AP, Li PL (2005) Activation of NAD(P)H oxidase by outward movements of H+ ions in renal medullary thick ascending limb of Henle. Am J Physiol Renal Physiol 289(5):F1048–F1056CrossRefGoogle Scholar
  28. 28.
    Katsuno K, Burrows JN, Duncan K, van Huijsduijnen RH, Kaneko T, Kita K, Schmatz D, Warner P, Slingsby BT (2015) Hit and lead criteria in drug discovery for infectious diseases of the developing world. Nat Rev Drug Discov 14:751–758CrossRefGoogle Scholar
  29. 29.
    Gao W, Kim JY, Anderson JR, Akopian T, Hong S, Jin YY, Kandror O, Kim JW, Lee IA, Lee SY, McAlpine JB, Mulugeta S, Sunoqrot S, Wang Y, Yang SH, Yoon TM, Goldberg AL, Pauli GF, Suh JW, Franzblau SG, Cho S (2014) The cyclic peptide ecumicin targeting ClpC1 is active against Mycobacterium tuberculosis in vivo. Antimicrobial Agents Chemother 59(2):880–889CrossRefGoogle Scholar
  30. 30.
    Lee H, Suh JW (2016) Anti-tuberculosis lead molecules from natural products targeting Mycobacterium tuberculosis ClpC1. J Ind Microbiol Biotechnol 43(2–3):205–212CrossRefGoogle Scholar
  31. 31.
    Tacar O, Sriamornsak P, Dass CRJ (2013) Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 65(2):157–170CrossRefGoogle Scholar
  32. 32.
    Gullón S, Olano C, Abdelfattah MS, Braña AF, Rohr J, Méndez C, Salas JA (2006) Isolation, characterization, and heterologous expression of the biosynthesis gene cluster for the antitumor anthracycline steffimycin. Appl Environ Microbiol 72(6):4172–4183CrossRefGoogle Scholar
  33. 33.
    Gajadeera C, Willby MJ, Green KD, Shaul P, Fridman M, Garneau-Tsodikova S, Posey JE, Tsodikov OV (2015) Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG. J Antibiot (Tokyo) 68(3):153–157CrossRefGoogle Scholar
  34. 34.
    Andries K, Verhasselt P, Guillemont J, Göhlmann HW, Neefs JM, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier VA (2005) A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307(5707):223–227CrossRefGoogle Scholar
  35. 35.
    Diacon AH, Dawson R, Hanekom M, Narunsky K, Venter A, Hittel N, Geiter LJ, Wells CD, Paccaly AJ, Donald PR (2011) Early bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients. Int J Tuberc Lung Dis 15(7):949–954CrossRefGoogle Scholar
  36. 36.
    Cragg GM, Grothaus PG, Newman DJ (2014) New horizons for old drugs and drug leads. J Nat Prod 77(3):703–723CrossRefGoogle Scholar
  37. 37.
    D’Ambrosio L, Centis R, Sotgiu G, Pontali E, Spanevello A, Migliori GB (2015) New anti-tuberculosis drugs and regimens: 2015 update. ERJ Open Res 1(1):00010–2015PubMedPubMedCentralGoogle Scholar
  38. 38.
    Hartkoorn RC, Sala C, Neres J, Pojer F, Magnet S, Mukherjee R, Uplekar S, Boy-Röttger S, Altmann K-H, Cole ST (2012) Towards a new tuberculosis drug: pyridomycin – nature’s isoniazid. EMBO Mol Med 4(10):1032–1042CrossRefGoogle Scholar
  39. 39.
    Pang Y, Lu J, Wang Y, Song Y, Wang S, Zhao Y (2013) Study of the rifampin monoresistance mechanism in Mycobacterium tuberculosis. Antimicrob Agents Chemother 57:893–900CrossRefGoogle Scholar
  40. 40.
    Reusser F (1975) Steffimycin B, a DNA binding agent. Biochim Biophys Acta Nucleic Acids Protein Synthesis 383(3):266–273CrossRefGoogle Scholar
  41. 41.
    Wang AH-J (1992) Intercalative drug binding to DNA. Curr Opin Struct Biol 2:361–368CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Miriam Trenado-Uribe
    • 1
  • Mayra Silva-Miranda
    • 1
  • José F. Rivero-Cruz
    • 2
  • Karol Rodríguez-Peña
    • 1
  • Clara I. Espitia-Pinzón
    • 1
  • Romina Rodríguez-Sanoja
    • 1
  • Sergio Sánchez
    • 1
  1. 1.Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de México (UNAM), Ciudad UniversitariaMexico CityMexico
  2. 2.Facultad de QuímicaUNAM, Ciudad UniversitariaMexico CityMexico

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