Skip to main content
SpringerLink
Log in

Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

  • Fungal Microbiology
  • Published:
Microbial Ecology Aims and scope Submit manuscript

Abstract

During the screening of endophytes obtained from Glycyrrhiza glabra Linn., the extract from a fungal culture designated as GG1F1 showed significant antimicrobial activity. The fungus was identified as a species of the genus Phoma and was most closely related to Phoma cucurbitacearum. The chemical investigation of the GG1F1 extract led to the isolation and characterization of two thiodiketopiperazine derivatives. Both the compounds inhibited the growth of several bacterial pathogens especially that of Staphylococcus aureus and Streptococcus pyogenes, with IC50 values of less than 10 μM. The compounds strongly inhibited biofilm formation in both the pathogens. In vitro time kill kinetics showed efficient bactericidal activity of these compounds. The compounds were found to act synergistically with streptomycin while producing varying effects in combination with ciprofloxacin and ampicillin. The compounds inhibited bacterial transcription/translation in vitro, and also inhibited staphyloxanthin production in S. aureus. Although similar in structure, they differed significantly in some of their properties, particularly the effect on the expression of pathogenecity related genes in S. aureus at sub-lethal concentrations. Keeping in view the antimicrobial potential of these compounds, it would be needful to scale up the production of these compounds through fermentation technology and further explore their potential as antibiotics using in vivo models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Reinhold-Hurek B, Hurek T (2011) Living in side plants: bacterial endophytes. Curr Opin Plant Biol 14(4):435–443

    Article  PubMed  Google Scholar 

  2. Iqbal J, Nelson JA, McCulley RL (2013) Fungal endophyte presence and genotype affect plant diversity and soil-to-atmosphere trace gas fluxes. Plant Soil 364(1):15–27

    Article  CAS  Google Scholar 

  3. Wani ZA, Ashraf N, Mohiuddin T, Riyaz-Ul-Hassan S (2015) Plant-endophyte symbiosis, an ecological perspective. Appl Microbiol Biotechnol 99(7):2955–2965

    Article  CAS  PubMed  Google Scholar 

  4. Strobel G, Daisy B, Castillo U, Harper J (2004) Natural products from endophytic microorganisms. J Nat Prod 67(2):257–268

    Article  CAS  PubMed  Google Scholar 

  5. Porras-Alfaro A, Bayman P (2011) Hidden fungi, emergent properties: endophytes and microbiomes. Annu Rev Phytopathol 49:291–315

    Article  CAS  PubMed  Google Scholar 

  6. Nalli Y, Mirza DN, Wani ZA, Wadhwa B, Mallik FA, Raina C, Chaubey A, Riyaz-Ul-Hassan S, Ali A (2015) Phialomustin A-D, new antimicrobial and cytotoxic metabolites from an endophytic fungus, Phialophora mustea. RSC Adv 5(115):95307–95312

    Article  CAS  Google Scholar 

  7. Aly AH, Debbab A, Proksch P (2011) Fungal endophytes: unique plant inhabitants with great promises. Appl Microbiol Biotechnol 90(6):1829–1845

    Article  CAS  PubMed  Google Scholar 

  8. Mousa WK, Raizada MN (2013) The diversity of anti-microbial secondary metabolites produced by fungal endophytes: an interdisciplinary perspective. Front Microbiol 4:65

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagacé-Wiens PR, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch JP, Karlowsky JA (2014) Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs 74(1):31–51

    Article  CAS  PubMed  Google Scholar 

  10. Gould K (2016) Antibiotics: from prehistory to the present day. J Antimicrob Chemother 71(3):572–275

    Article  CAS  PubMed  Google Scholar 

  11. Hosseinzadeh H, Nassiri-Asl M (2015) Pharmacological effects of Glycyrrhiza spp. and its bioactive constituents: update and review. Phytother Res 29(12):1868–1886

    Article  PubMed  Google Scholar 

  12. Curreli F, Friedman-Kien AE, Flore O (2005) Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes. J Clin Invest 115(3):642–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang MZ, Xu J, Yao B, Yin H, Cai Q, Shrubsole MJ, Chen X, Kon V, Zheng W, Pozzi A, Harris RC (2009) Inhibition of 11beta-hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans. J Clin Invest 119(4):876–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Afnan Q, Adil MD, Nissar-Ul A, Rafiq AR, Amir HF, Kaiser P, Gupta VK, Vishwakarma R, Tasduq SA (2012) Glycyrrhizic acid (GA), a triterpenoid saponin glycoside alleviates ultraviolet-B irradiation-induced photoaging in human dermal fibroblasts. Phytomedicine 19(7):658–664

    Article  CAS  PubMed  Google Scholar 

  15. Ikeda K, Arase Y, Kobayashi M, Saitoh S, Someya T, Hosaka T, Sezaki H, Akuta N, Suzuki Y, Suzuki F, Kumada H (2006) A long-term glycyrrhizin injection therapy reduces hepatocellular carcinogenesis rate in patients with interferon-resistant active chronic hepatitis C: a cohort study of 1249 patients. Dig Dis Sci 51(3):603–609

    Article  CAS  PubMed  Google Scholar 

  16. Ezra D, Hess WH, Strobel GA (2004) New endophytic isolates of M. albus, a volatile antibiotic-producing fungus. Microbiology 150(12):4023–4031

    Article  CAS  PubMed  Google Scholar 

  17. Qadri M, Rajput R, Abdin MZ, Vishwakarma RA, Riyaz-Ul-Hassan S (2014) Diversity, molecular phylogeny and bioactive potential of fungal endophytes associated with the Himalayan blue pine (Pinus wallichiana). Microb Ecol 67(4):877–887

    Article  PubMed  Google Scholar 

  18. White TJ, Bruns T, Lee S, Taylor J (1990) Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. PCR protocols: a guide to methods and applications 18(1):315–322

    Google Scholar 

  19. Altschul SF, Madden TL, Schaffer AA, Zhang JH, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tamura K, Nei M (1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol 10(3):512–526

    CAS  PubMed  Google Scholar 

  21. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 30(12):2725–2729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ellof JN (1998) A sensitive and quick microplate method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med 64(8):711–713

    Article  Google Scholar 

  23. O'toole GA, Pratt LA, Watnick PI, Newman DK, Weaver VB, Kolter R (1999) Genetic approaches to study of biofilms. Methods Enzymol 310:91–106

    Article  PubMed  Google Scholar 

  24. Wayne PA (2006) Clinical and laboratory standards institute: methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard M7-A7, CLSI, USA

  25. Craig WA, Gudmundsson S (1996) Postantibiotic effect. In: Lorian V (ed) Antibiotics in laboratory medicine, 4th edn. Williams and Wilkins Co, Baltimore, pp 296–329

    Google Scholar 

  26. Odds FC (2003) Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52(1):1

    Article  CAS  PubMed  Google Scholar 

  27. Song Y, Liu CI, Lin FY, No JH, Hensler M, Liu YL, Jeng WY, Low J, Liu GY, Nizet V, Wang AHJ, Oldfield E (2009) Inhibition of staphyloxanthin virulence factor biosynthesis in Staphylococcus aureus: in vitro, in vivo, and crystallographic results. J Med Chem 52(13):3869–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Qiu J, Zhang X, Luo M, Li H, Dong J, Wang J, Leng B, Wang X, Feng H, Ren W, Deng X (2011) Subinhibitory concentrations of perilla oil affect the expression of secreted virulence factor genes in Staphylococcus aureus. PLoS One 6(1):e16160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Feng Y, Blunt JW, Cole AL, Munro MH (2004) Novel cytotoxic thiodiketopiperazine derivatives from a Tilachlidium sp. J Nat Prod 67(12):2090–2092

    Article  CAS  PubMed  Google Scholar 

  30. Monte E, Bridge PD, Sutton BC (1991) An integrated approach to Phoma systematics. Mycopathologia 115(2):89–103

    Article  Google Scholar 

  31. Strobel G, Singh SK, Riyaz-Ul-Hassan S, Mitchel AM, Geary B, Sears J (2011) An endophytic/pathogenic Phoma sp. from creosote bush producing biologically active volatile compounds having fuel potential. FEMS Microbiol Lett 320(2):87–94

    Article  CAS  PubMed  Google Scholar 

  32. Mousa WK, Schwan A, Davidson J, Strange P, Liu H, Zhou T, Auzanneau FI, Raizada MN (2015) An endophytic fungus isolated from finger millet (Eleusine coracana) produces anti-fungal natural products. Front Microbiol 6:1157

    Article  PubMed  PubMed Central  Google Scholar 

  33. Stewart JE, Turner AN, Brewer MT (2015) Evolutionary history and variation in hostrange of three Stagonosporopsis species causing gummy stem blight of cucurbits. Fungal Biol 119(5):370–382

    Article  PubMed  Google Scholar 

  34. Shim SH, Baltrusaitis J, Gloer JB, Wicklow DT (2011) Phomalevones A-C: dimeric and pseudodimeric polyketides from a fungicolous Hawaiian isolate of Phoma sp. (Cucurbitariaceae). J Nat Prod 74(3):395–401

    Article  CAS  PubMed  Google Scholar 

  35. Wang FZ, Huang Z, Shi XF, Chen YC, Zhang WM, Tian XP, Li J, Zhang S (2012) Cytotoxic indole diketopiperazines from the deep sea-derived fungus Acrostalagmus luteoalbus SCSIO F457. Bioorg Med Chem Lett 22(23):7265–7267

    Article  CAS  PubMed  Google Scholar 

  36. DeLorbe JE, Horne D, Jove R, Mennen SM, Nam S, Zhang FL, Overman LE (2013) General approach for preparing epidithiodioxopiperazines from trioxopiperazine precursors: enantioselective total syntheses of (+)- and (−)-gliocladine C, (+)-leptosin D, (+)-T988C, (+)-bionectin A, and (+)-gliocladin A. J Am Chem Soc 135(10):4117–4128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Carr G, Tay W, Bottriell H, Andersen SK, Mauk AG, Andersen RJ (2009) Plectosphaeroic acids A, B, and C, indoleamine 2,3-dioxygenase inhibitors produced in culture by a marine isolate of the fungus Plectosphaerella cucumerina. Org Lett 11(14):2996–2999

    Article  CAS  PubMed  Google Scholar 

  38. Wang LW, Xu BG, Wang JY, Su ZZ, Lin FC, Zhang CL, Kubicek CP (2012) Bioactive metabolites from Phoma species, an endophytic fungus from the Chinese medicinal plant Arisaema erubescens. Appl Microbiol Biotechnol 93(3):1231–1239

    Article  CAS  PubMed  Google Scholar 

  39. Boles BR, Horswill AR (2008) agr-Mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathog 4(4):e1000052

    Article  PubMed  PubMed Central  Google Scholar 

  40. Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, Fierer J, Nizet V (2005) Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med 202(2):209–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kuroda H, Kuroda M, Cui L, Hiramatsu K (2007) Subinhibitory concentrations of beta-lactam induce haemolytic activity in Staphylococcus aureus through the SaeRS two-component system. FEMS Microbiol Lett 268:98–105

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the CSIR 12th FYP project (Grant number: PMSI-BSC0117) of the Council of Scientific and Industrial Research (CSIR), New Delhi, India, and the Major Lab Project, MLP1008 of the institute. The first author is supported by Department of Science and Technology, New Delhi, India, through INSPIRE Senior Research Fellowship. We are grateful to Dr. Suphla Gupta for providing the plant material. The article bears the institutional manuscript no. IIIM/1934/2016.

Author information

Authors and Affiliations

  1. Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India

    Palak Arora, Zahoor A. Wani & Syed Riyaz-Ul-Hassan

  2. Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India

    Palak Arora, Zahoor A. Wani, Yedukondalu Nalli, Asif Ali & Syed Riyaz-Ul-Hassan

  3. Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India

    Yedukondalu Nalli & Asif Ali

Authors
  1. Palak Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zahoor A. Wani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yedukondalu Nalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Asif Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Syed Riyaz-Ul-Hassan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Asif Ali or Syed Riyaz-Ul-Hassan.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 997 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arora, P., Wani, Z.A., Nalli, Y. et al. Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.. Microb Ecol 72, 802–812 (2016). https://doi.org/10.1007/s00248-016-0805-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00248-016-0805-x

Keywords

Search

Navigation