Applied Microbiology and Biotechnology

, Volume 89, Issue 4, pp 931–937 | Cite as

Exploitation of phage battery in the search for bioactive actinomycetes



Screening of microbial natural products continues to represent an important route to the discovery of novel bioactive compounds for the development of new therapeutic agents, and actinomycetes are still the major producers of biopharmaceuticals. Selective isolation of bioactive actinomycete species, in particular the rare ones, has thus become a target for industrial microbiologists. In this context, bacteriophages have proven to be useful tools as (1) naturally present indicators of under-represented or rare actinomycete taxa in environmental samples, (2) indicators of the relatedness of bioactive taxa in target-directed search and discovery, (3) de-selection agents of unwanted taxa on isolation plates in target-specific search for rare actinomycete taxa, (4) tools in screening assays for specific targets. Against this background, a number of case studies are presented to illustrate the use of bacteriophages as tools in actinomycete-origin bioactive compound search and discovery programs.


Actinomycetes Bioactive compounds Bacteriophages Selective isolation of rare actinomycetes 


  1. Allison HE (2007) Stx-phages: drivers and mediators of the evolution of STEC and STEC-like pathogens. Future Microbiol 2:165–174CrossRefGoogle Scholar
  2. Baltz RH (2005) Antibiotic discovery from actinomycetes: will a renaissance follow the decline and fall? SIM News 55(5):186–196Google Scholar
  3. Baltz RH (2006) Marcel Faber Roundtable: is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration. J Ind Microbiol Biotech 33:507–513CrossRefGoogle Scholar
  4. Bérdy J (2005) Bioactive microbial metabolites. J Antibiot 58(1):1–26CrossRefGoogle Scholar
  5. Bergh O, Borsheim KY, Brathak G, Heidal M (1989) High abundance of viruses found in aquatic environments. Nature 340:467–468CrossRefGoogle Scholar
  6. Bull AT (ed) (2003) Microbial diversity and bioprospecting. ASM, WashingtonGoogle Scholar
  7. Bull AT (2007) Alice in Actinoland, and looking glass tales. SIM News 57(6):225–234Google Scholar
  8. Bull AT, Ward AC, Goodfellow M (2000) Search and discovery strategies for biotechnology: the paradigm shift. Microbiol Mol Biol Rev 64:573–606CrossRefGoogle Scholar
  9. Chibani-Chennoufi S, Bruttin A, Dillmann M-L, Brüssow H (2004) Phage–host interaction; an ecological perspective. J Bacteriol 186(12):3677–3686CrossRefGoogle Scholar
  10. Clardy J, Fischbach MA, Walsh CT (2006) New antibiotics from bacterial natural products. Nat Biotechnol 24(12):1541–1550CrossRefGoogle Scholar
  11. Demain AL (2000) Small bugs, big business: the economic power of the microbe. Biotechnol Adv 18:499–514CrossRefGoogle Scholar
  12. Goodfellow M, Williams E (1986) New strategies for the selective isolation of industrially important bacteria. Biotechnol Genet Eng Rev 4:213–262Google Scholar
  13. Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13(19/20):894–901CrossRefGoogle Scholar
  14. Hayakawa M (2003) Selective isolation of rare actinomycete genera using pretreatment techniques. In: Kurtböke DI (ed) Selective isolation of rare actinomycetes. Queensland Complete Printing Services, NambourGoogle Scholar
  15. Henkel T, Brunne R, Muller H, Reichel F (1999) Statistical investigation into the structural complementarity of natural products and synthetic compounds. Angew Chem Int Ed Engl 38:643–647CrossRefGoogle Scholar
  16. Jensen PR, Mafnas C (2006) Biogeography of the marine actinomycete Salinispora. Environ Microbiol 8(11):1881–1888CrossRefGoogle Scholar
  17. Kılıç AO, Pavlova SI, Alpay S, Kılıç SS, Tao L (2001) Comparative study of vaginal Lactobacillus phages isolated from women in the United States and Turkey: prevalence, morphology, host range, and DNA homology. Clin Diagn Lab Immunol 8:31–39Google Scholar
  18. Knight V, Sanglier J-J, DiTullio D, Braccili S, Bonner P, Waters J, Hughes D, Zhang L (2003) Diversifying microbial natural products for drug discovery. Appl Microbiol Biotechnol 63:446–458CrossRefGoogle Scholar
  19. König A, Schwecke T, Molnár I, Böhm GA, Lowden PAS, Staunton J, Leadley PF (1997) The pipecolate-incorporating enzyme for biosynthesis of the immunosuppressant rapamycin. Eur J Biochem 247:526–534CrossRefGoogle Scholar
  20. Kurtböke DI (2003a) Use of bacteriophages for the selective isolation of rare actinomycetes. In: Kurtböke DI (ed) Selective isolation of rare actinomycetes. Queensland Complete Printing Services, NambourGoogle Scholar
  21. Kurtböke DI (ed) (2003b) Selective isolation of rare actinomycetes. Queensland Complete Printing Services, NambourGoogle Scholar
  22. Kurtböke DI (2005) Actinophages as indicators of actinomycete taxa in marine environments. Antonie van Leeuwenhoek 87:19–28CrossRefGoogle Scholar
  23. Kurtböke DI (2009) Use of phage-battery to isolate industrially important rare actinomycetes. In: Adams HT (ed) Contemporary trends in bacteriophage research. NOVA Science, New YorkGoogle Scholar
  24. Kurtböke DI (2010) Bacteriophages as tools in drug discovery programs. Microbiol Aust 31(2):67–70Google Scholar
  25. Kurtböke DI, French JRJ (2007) Use of phage battery to investigate the actinofloral layers of termite-gut microflora. J Appl Microbiol 103(3):722–734CrossRefGoogle Scholar
  26. Kurtböke DI, Williams ST (1991) Use of actinophage for selective isolation purposes: current problems. Actinomycetes 2(2):31–36Google Scholar
  27. Kurtböke DI, Chen C-F, Williams ST (1992) Use of polyvalent phage for reduction of streptomycetes on soil dilution plates. J Appl Bacteriol 72:103–111Google Scholar
  28. Kurtböke DI, Murphy NE, Sivasithamparam K (1993a) Use of bacteriophage for the selective isolation of thermophilic actinomycetes from composted eucalyptus bark. Can J Microbiol 39:46–51CrossRefGoogle Scholar
  29. Kurtböke DI, Wilson CR, Sivasithamparam K (1993b) Occurrence of Actinomadura phage in organic mulches used for avocado plantations in Western Australia. Can J Microbiol 39:389–394CrossRefGoogle Scholar
  30. Letellier L, Boulanger P, Plançon L, Jacquot P, Santamaria M (2004) Main features on tailed phage, host recognition and DNA uptake. Front Biosci 9:1228–1239CrossRefGoogle Scholar
  31. Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66(7):1022–1037CrossRefGoogle Scholar
  32. Nodwell JR (2007) Novel links between antibiotic resistance and antibiotic production. J Bacteriol 189(10):3683–3685CrossRefGoogle Scholar
  33. Okazaki T (2003) Studies on actinomycetes isolated from plant leaves. In: Kurtböke DI (ed) Selective isolation of rare actinomycetes. Queensland Complete Printing Services, NambourGoogle Scholar
  34. Osada H (1995) Fascinating bioactive compounds from actinomycetes. Actinomycetol 9:254–262CrossRefGoogle Scholar
  35. Osada H, Yano T, Koshino H, Isono K (1991) Enopeptin A, a novel depsipeptide antibiotic with antibacteriophage activity. J Antibiot 44:1463–1466Google Scholar
  36. Peláez F (2006) The historical delivery of antibiotics from microbial natural products—can history repeat? Biochem Pharmacol 71:981–990CrossRefGoogle Scholar
  37. Terekhova L (2003) Isolation of actinomycetes with the use of microwaves and electric pulses. In: Kurtböke DI (ed) Selective isolation of rare actinomycetes. Queensland Complete Printing Services, NambourGoogle Scholar
  38. Thomas J, Soddell J, Kurtböke DI (2002) Fighting foam with phages? Water Sci Technol 46(1–2):511–518Google Scholar
  39. von Nussbaum F, Brands M, Hinzen B, Weigand S, Häbich D (2006) Antibacterial natural products in medicinal chemistry—exodus or revival? Angew Chem Int Ed Engl 45:5072–5129CrossRefGoogle Scholar
  40. Ward A, Goodfellow M (2004) Taxonomy as a roadmap for search and biodiscovery. Microbiol Aust 25:13–15Google Scholar
  41. Waterbury JB, Valois FW (1993) Resistance to co-occurring phages enables marine Synechococcus communities to coexist with cyanophages abundant in seawater. Appl Environ Microbiol 59:3393–3399Google Scholar
  42. Watve MG, Tickoo R, Jog MM, Behole BD (2001) How many antibiotics are produced by the genus Streptomyces? Arch Microbiol 176:386–390CrossRefGoogle Scholar
  43. Williams ST, Vickers JC, Goodfellow M (1984) New microbes from old habitats? In: Kelly DP, Carr NG (eds) The microbe 1984, II: prokaryotes and eukaryotes. Cambridge University Press, Cambridge, pp 219–256Google Scholar
  44. Williams ST, Locci R, Beswick A, Kurtböke DI, Kuznetsov VD, Le Monnier FJ, Long PF, Maycroft KA, Palmit RA, Petrolini B, Quaroni S, Todd JI, West M (1993) Detection and identification of novel actinomycetes. Res Microbiol 144:653–656CrossRefGoogle Scholar
  45. Williams PG, Buchanan GO, Feling RH, Kauffman CA, Jensen PJ, Fenical W (2005) New cytotoxic salinosporamides from marine actinomycete Salinispora tropica. J Org Chem 70(16):6196–6203CrossRefGoogle Scholar
  46. Wommack KE, Hill RT, Müller TA, Colwell RR (1996) Effects of sunlight on bacteriophage viability and structure. Appl Environ Microbiol 62:1336–1341Google Scholar
  47. Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW (2000) Quinolone antibiotics induce shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 181:664–670CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Faculty of Science, Health and EducationUniversity of the Sunshine CoastMaroochydore DCAustralia

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