1887

Abstract

The antibacterial activity of the nitrogen heterocyclic sponge constituent cribrostatin 6 was examined. Cribrostatin 6 was bacteriostatic for a variety of Gram-positive species and was bactericidal for the majority of clinical isolates of , including penicillin-resistant strains. Minimum bactericidal concentration/MIC ratios were ⩽2 for 75 % of clinical isolates. Kill-curve analysis confirmed the bactericidal action of cribrostatin 6. Bactericidal activity was rather slow, beginning at 2, 4 or 8 h, depending on the strain. The frequency of occurrence of bacterial spontaneous mutations to resistance was ⩽10. The maximum tolerated dose of cribrostatin 6 in mice was 750–1000 μg kg day. Cribrostatin 6 is a promising lead antibiotic for Gram-positive bacteria, particularly , a leading cause of infection and mortality worldwide.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.05250-0
2004-01-01
2020-10-29
Loading full text...

Full text loading...

/deliver/fulltext/jmm/53/1/JM530110.html?itemId=/content/journal/jmm/10.1099/jmm.0.05250-0&mimeType=html&fmt=ahah

References

  1. Amsterdam D. 1996; Susceptibility testing of antimicrobials in liquid media. In Antibiotics in Laboratory Medicine , 4th edn. pp 52–111 Edited by Lorian V. Baltimore: Williams & Wilkins;
    [Google Scholar]
  2. Calabresi P., Goulette F. A., Darnowski J. W. 2001; Taurolidine: cytotoxic and mechanistic evaluation as a novel antineoplastic agent. Cancer Res 61:6816–6821
    [Google Scholar]
  3. Cardenas M. E., Cruz M. C., Del Poeta M., Chung N., Perfect J. R., Heitman J. 1999; Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action. Clin Microbiol Rev 12:583–611
    [Google Scholar]
  4. Doern G. V., Heilmann K. P., Huynh H. K., Rhomberg P. R., Coffman S. L., Brueggemann A. B. 2001; Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999–2000, including a comparison of resistance rates since 1994–1995. Antimicrob Agents Chemother 45:1721–1729 [CrossRef]
    [Google Scholar]
  5. Greenwood B. 1999; The epidemiology of pneumococcal infection in children in the developing world. Philos Trans R Soc Lond B Biol Sci 354:777–785 [CrossRef]
    [Google Scholar]
  6. Liu Y., Ryan M. E., Lee H. M., Simon S., Tortora G., Lauzon C., Leung M. K., Golub L. M. 2002; A chemically modified tetracycline (CMT-3) is a new antifungal agent. Antimicrob Agents Chemother 46:1447–1454 [CrossRef]
    [Google Scholar]
  7. Lokeshwar B. L., Houston-Clark H. L., Selzer M. G., Block N. L., Golub L. M. 1998; Potential application of a chemically modified non-antimicrobial tetracycline (CMT-3) against metastatic prostate cancer. Adv Dent Res 12:97–102 [CrossRef]
    [Google Scholar]
  8. Musher D. M. 1992; Infections caused by Streptococcus pneumoniae : clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis 14:801–807 [CrossRef]
    [Google Scholar]
  9. NCCLS 2000 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically . Approved standard M7-A5 Villa Nova, PA: National Committee for Clinical Laboratory Standards;
    [Google Scholar]
  10. Pettit G. R., Knight J. C., Collins J. C., Herald D. L., Pettit R. K., Boyd M. R., Young V. G. 2000; Antineoplastic agents 430.Isolation and structure of cribrostatins 3, 4, and 5 from the Republic of Maldives Cribrochalina species. J Nat Prod 63:793–798 [CrossRef]
    [Google Scholar]
  11. Pettit G. R., Collins J. C., Knight J. C., Herald D. L., Nieman R. A., Williams M. D., Pettit R. K. 2003; Antineoplastic agents 485.Isolation and structure of cribrostatin 6, a dark blue cancer cell growth inhibitor from the marine sponge Cribrochalina sp. J Nat Prod 66:544–547 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.05250-0
Loading
/content/journal/jmm/10.1099/jmm.0.05250-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error