Antimicrobial activity and biosynthesis of indole antibiotics produced by Free

Abstract

We have investigated the mechanism of action and physiology of production of the indole derivative antibiotics produced by the nematode-associated, entomopathogenic bacterium . Maximum antibiotic concentration was reached during the late stationary phase of growth, and the antibiotic yield was appreciably enhanced by supplementation with tryptophan. Antibiotic biosynthesis apparently involved the removal of the side-chain carboxyl (C-1) carbon of tryptophan. The C-3 methylene carbon of tryptophan, on the other hand, was retained. The purified indole antibiotic was effective against both Gram-positive and Gram-negative bacteria at low to moderate concentrations causing a severe inhibition of RNA synthesis, accompanied by a less severe effect on protein synthesis. An isogenic pair of strains differing at the locus was used to demonstrate that the swift reduction in total RNA synthesis is related to an antibiotic-induced accumulation of the regulatory nucleotide, ppGpp, in susceptible bacteria. The mutant, which does not exhibit any discernible increase in ppGpp upon antibiotic treatment, showed no decrease in growth or RNA synthesis. Using this antibiotic, it was also observed that ppGpp may be employed as a metabolic regulator in bacteria such as which have not previously been reported to employ ppGpp as a regulatory molecule. We propose that the indole derivative antibiotic exerts growth inhibitory control in susceptible bacteria by greatly enhancing synthesis of ppGpp, resulting in a rapid inhibition of RNA synthesis.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-139-12-3139
1993-12-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/139/12/mic-139-12-3139.html?itemId=/content/journal/micro/10.1099/00221287-139-12-3139&mimeType=html&fmt=ahah

References

  1. Akhurst R.J. 1980; Morphological and physiological dimorphism in Xenorhabdus spp., bacteria symbiotically associated with the insect pathogenic nematodes Neoaplectana and Heterorhabditis. Journal of General Microbiology 121:303–309
    [Google Scholar]
  2. Akhurst R.J. 1982; Antibiotic activity of Xenorhabdus spp., bacteria symbiotically associated with insect pathogenic nematodes of the families Heterorhabditidae and Steinernematidae. Journal of General Microbiology 128:3061–3065
    [Google Scholar]
  3. Akhurst R.J., Boemare N.E. 1988; A numerical taxonomic study of the genus Xenorhabdus and proposed elevation of the subspecies of X. nematophilus to species. Journal of General Microbiology 134:1835–1845
    [Google Scholar]
  4. Bedding R.A. 1981; Low cost in vitro mass production of Neoaplectana and Heterorhabditis species (Nematoda) for field control of insect pests. Nematologica 27:109–114
    [Google Scholar]
  5. Bedding R.A. 1984; Large scale production, storage and transport of the insect parasitic nematodes Neoaplectana spp. and Heterorhabditis spp. Annals of Applied Biology 104:117–120
    [Google Scholar]
  6. Bedding R.A., Molyneux A.S. 1982; Penetration of insect cuticle by infective juveniles of Heterorhabditis spp. (Heterorhabditidae: Nematoda). Nematologica 28:354–359
    [Google Scholar]
  7. Boemare N.E., Akhurst R.J. 1988; Biochemical and physiological characterization of colony form variants in Xenorhabdus spp.(Enterobacteriaceae). Journal of General Microbiology 134:751–761
    [Google Scholar]
  8. Burman M. 1982; Neoaplectana carpocapsae: toxin production by axenic insect parasitic nematodes. Nematologica 28:62–70
    [Google Scholar]
  9. Cashel M. 1969; The control of ribonucleic acid synthesis in Escherichia coli. IV. Relevance of unusual phosphorylated compounds from amino acid starved stringent strains. Journal of Biological Chemistry 244:3133–3141
    [Google Scholar]
  10. Chang F.N, Chang C.N, Paik W.K. 1974; Methylation of ribosomal proteins in Escherichia coli. Journal of Bacteriology 120:651–656
    [Google Scholar]
  11. Couche G.A., Gregson R.P. 1987; Protein inclusions produced by the entomopathogenic bacteria Xenorhabdus nematophilus subsp.nematophilus. Journal of Bacteriology 169:5279–5288
    [Google Scholar]
  12. Couche G.A., Lehrbach P.R., Forage R.G., Cooney G.C., Smith D.R., Gregson R.P. 1987; Occurrence of intracellular inclusions and plasmids in Xenorhabdus spp. Journal of General Microbiology 133:967–973
    [Google Scholar]
  13. Gallant J., Shell L., Bittner R. 1976; A novel nucleotide implicated in the response of Escherichia coli to energy italic downshift. Cell 7:75–84
    [Google Scholar]
  14. Gotz P., Boman A., Boman H.G. 1981; Interactions between insect immunity and an insect-pathogenic nematode with symbiotic bacteria. Proceedings of the Royal Society B212:333–350
    [Google Scholar]
  15. Gregson R.P., Mcinerney B.V. 1985; Xenocoumacins. Australian Patent PCT/AU85/00215.
    [Google Scholar]
  16. Khan A., Brooks W. 1977; A chromogenic bioluminescent bacterium associated with the entomophilic nematode Chromonema heliothidis. Journal of Invertebrate Pathology 29:253–261
    [Google Scholar]
  17. Lagosky P.A., Chang F.N. 1978; The extraction of guanosine 5ʹ-diphosphate, 3ʹ-diphosphate (ppGpp) from Escherichia coli using low pH reagents: a reevaluation. Biochemical and Biophysical Research Communications 84:1016–1020
    [Google Scholar]
  18. Lagosky P.A., Chang F.N. 1981; Correlation between RNA synthesis and basal level guanosine 5ʹ-diphosphate 3ʹ-diphosphate in relaxed mutants of Escherichia coli. Journal of Biological Chemistry 256:11651–11656
    [Google Scholar]
  19. Leavitt R.I., Umbarger H.E. 1962; Isoleucine and valine metabolism in Escherichia coli. XI. Valine inhibition of the growth of Escherichia coli strain K12. Journal of Bacteriology 83:624–630
    [Google Scholar]
  20. Lipmann F., Sy J. 1976; The enzymatic mechanism of guanosine 5ʹ,3ʹ-polyphosphate synthesis. In Progress in Nucleic Acid Research and Molecular Biology 17 pp. 1–4 Cohn W.E. Edited by New York: Academic Press;
    [Google Scholar]
  21. Lowen P.C. 1976; Novel nucleotides isolated from Escherichia coli isolated and partially characterized. Biochemical and Biophysical Research Communications IQ1210–1218
    [Google Scholar]
  22. Lysenko O., Weiser J. 1974; Bacteria associated with the nematode Neoaplectana carpocapsae and the pathogenicity of this complex for Galleria mellonella larvae. Journal of Invertebrate Pathology 24:332–336
    [Google Scholar]
  23. Nealson K.H., Schmidt T.M., Bleakley B. 1988; Luminescent bacteria: symbionts of nematodes and pathogens of insects. In Cell to Cell Signals in Plant, Animal and Microbial Symbiosis. NATO ASI series H17 pp. 101–123 Scannerini S. Edited by Berlin: Springer-Verlag;
    [Google Scholar]
  24. Paul V.J., Frautschy S., Fenical W., Nealson K.H. 1981; Antibiotics in microbial ecology: isolation and structure assignment of several new antibacterial compounds from the insect-symbiotic bacteria Xenorhabdus spp. Journal of Chemical Ecology 1:589–597
    [Google Scholar]
  25. Poinar G.O. 1966; The presence of Achromobacter nematophilus in the infectious stage of a Neoaplectana sp.(Steinernematidae: Nematoda). Nematologica 12:105–108
    [Google Scholar]
  26. Poinar G.O., Thomas G.M. 1966; Significance of Achromobacter nematophilus Poinar and Thomas (Achromobacteraceae: Eubacteri- ales) in the development of the nematode, DD-136 (Neoaplectana sp.Steinernematodae). Parasitology 56:510–514
    [Google Scholar]
  27. Poinar G.O., Thomas G.M. 1967; The nature of Achromobacter nematophilus as an insect pathogen. Journal of Invertebrate Pathology 9:510–514
    [Google Scholar]
  28. Poinar G.O., Thomas G.M., Hess R. 1977; Characteristics of the specific bacteria associated with Heterorhabditis bacteriophora (Heterorhabditidae: Rhabditida). Nematologica 23:97–102
    [Google Scholar]
  29. Rhodes S.H., Lyons G.R., Gregson R.P., Akhurst R.J., Lacey M.J. 1983; Xenorhabdin antibiotics. Australian Patent PCT/AU83/00156.
    [Google Scholar]
  30. Richardson W.H., Schmidt T.M., Nealson K.H. 1988; Identification of an anthraquinone pigment and a hydroxystilbene antibiotic from Xenorhabdus luminescens. Appied and Environmental Microbiology 54:1602–1605
    [Google Scholar]
  31. Schmidt T.M., Bleakley B., Nealson K.H. 1988; Character-ization of an extracellular protease from the insect pathogen Xenorhabdus luminescens. Appied and Environmental Microbiology 54:2793–2797
    [Google Scholar]
  32. Spizizen J. 1958; Transformation of biochemically deficient strains of Bacillus subtilis by deoxyribonucleate. Proceedings of the National Academy of Sciences of the United States of America 44:1072–1078
    [Google Scholar]
  33. Sundar L., Chang F.N. 1992; The role of guanosine 3ʹ,5ʹ-bis- pyrophosphate in mediating antimicrobial activity of the antibiotic 3,5-dihydroxy-4-ethyl-trans-stilbene. Antimicrobial Agents and Chemotherapy 36:2645–2651
    [Google Scholar]
  34. Sy J., Lipmann F. 1973; Identification of the synthesis of MSI as insertion of a phosphorylated group into the 3ʹ-position in guanosine 5ʹ-diphosphate. Proceedings of the National Academy of Sciences of the United States of America 70:306–309
    [Google Scholar]
  35. Thomas G.M., Poinar G.O. 1979; Xenorhabdus gen. nov., a genus of entomopathogenic, nematophilic bacteria of the family Enterobacteriaceae. International Journal of Systematic Bacteriology 29:352–360
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-139-12-3139
Loading
/content/journal/micro/10.1099/00221287-139-12-3139
Loading

Data & Media loading...

Most cited Most Cited RSS feed