J Med Microbiol International Journal of Systematic and Evolutionary Microbiology
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J Med Microbiol 53 (2004), 61-65; DOI: 10.1099/jmm.0.05250-0
© 2004 Society for General Microbiology
ISSN 0022-2615

Antibacterial activity of the marine sponge constituent cribrostatin 6

Robin K. Pettit1,2, Bridget R. Fakoury1, John C. Knight1, Christine A. Weber1, George R. Pettit1,3, Gary D. Cage4 and Sandy Pon1

1,2,3Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA

Correspondence Robin K. Pettit pettitr{at}asu.edu

Received March 11, 2003
Accepted September 19, 2003

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 Streptococcus pneumoniae, including penicillin-resistant strains. Minimum bactericidal concentration/MIC ratios were <=2 for 75 % of S. pneumoniae 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 <=10-7. The maximum tolerated dose of cribrostatin 6 in mice was 750–1000 µg kg-1 day-1. Cribrostatin 6 is a promising lead antibiotic for Gram-positive bacteria, particularly S. pneumoniae, a leading cause of infection and mortality worldwide.

Abbreviations: BMHII, Mueller–Hinton II (cation-adjusted) broth containing 3 % lysed horse blood; MBC, minimum bactericidal concentration; MTD, maximum tolerated dose.






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