This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fujii, K.
Right arrow Articles by Hosoe, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fujii, K.
Right arrow Articles by Hosoe, K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, Jul 1995, 1489-1492, Vol 39, No. 7
Copyright © 1995 by the American Society for Microbiology. All rights reserved.

Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648

K Fujii, H Saito, H Tomioka, T Mae and K Hosoe
Department of Microbiology and Immunology, Shimane Medical University, Japan.

The mechanism of antimicrobial activity of KRM-1648 (KRM), a new rifamycin derivative with potent antimycobacterial activity, was studied. Both KRM and rifampin (RMP) inhibited RNA polymerases from Escherichia coli and Mycobacterium avium at low concentrations: the 50% inhibitory concentrations (IC50s) of KRM and RMP for E. coli RNA polymerase were 0.13 and 0.10 micrograms/ml, respectively, while the IC50s for M. avium RNA polymerase were 0.20 and 0.07 microgram/ml. Both KRM and RMP exerted weak inhibitory activity against Mycobacterium fortuitum RNA polymerase, rabbit thymus RNA polymerases, E. coli DNA polymerase I, and two types of reverse transcriptases. Uptake of 14C- KRM by M. avium reached 18,000 dpm/mg (dry weight) 1.5 h after incubation, while uptake by E. coli cells was slight. KRM was much more effective in inhibiting uptake of 14C-uracil than was RMP (IC50 of KRM, 0.04 microgram/ml; IC50 of RMP, 0.12 microgram/ml). These findings suggest, first, that the potent antimycobacterial activity of KRM is due to inhibition of bacterial RNA polymerase and, second, that the activity of KRM against target organisms depends on target cell wall permeability.


This article has been cited by other articles:

  • Tsuji, B. T., Yang, J. C., Forrest, A., Kelchlin, P. A., Smith, P. F. (2008). In vitro pharmacodynamics of novel rifamycin ABI-0043 against Staphylococcus aureus. J Antimicrob Chemother 62: 156-160 [Abstract] [Full Text]  
  • Campbell, L. A., Kuo, C.-C., Suchland, R. J., Rothstein, D. M. (2008). Efficacy of Benzoxazinorifamycins in a Mouse Model of Chlamydia pneumoniae Lung Infection. Antimicrob. Agents Chemother. 52: 1855-1858 [Abstract] [Full Text]  
  • Chen, Y.-X., Cabana, B., Kivel, N., Michaelis, A. (2007). Effect of Food on the Pharmacokinetics of Rifalazil, a Novel Antibacterial, in Healthy Male Volunteers. J Clin Pharmacol 47: 841-849 [Abstract] [Full Text]  
  • Rothstein, D. M., Farquhar, R. S., Sirokman, K., Sondergaard, K. L., Hazlett, C., Doye, A. A., Gwathmey, J. K., Mullin, S., van Duzer, J., Murphy, C. K. (2006). Efficacy of Novel Rifamycin Derivatives against Rifamycin-Sensitive and -Resistant Staphylococcus aureus Isolates in Murine Models of Infection. Antimicrob. Agents Chemother. 50: 3658-3664 [Abstract] [Full Text]  
  • Suchland, R. J., Brown, K., Rothstein, D. M., Stamm, W. E. (2006). Rifalazil Pretreatment of Mammalian Cell Cultures Prevents Subsequent Chlamydia Infection. Antimicrob. Agents Chemother. 50: 439-444 [Abstract] [Full Text]  
  • Anton, P. M., O'Brien, M., Kokkotou, E., Eisenstein, B., Michaelis, A., Rothstein, D., Paraschos, S., Kelly, C. P., Pothoulakis, C. (2004). Rifalazil Treats and Prevents Relapse of Clostridium difficile-Associated Diarrhea in Hamsters. Antimicrob. Agents Chemother. 48: 3975-3979 [Abstract] [Full Text]  
  • Piddock, L. J. V., Ricci, V. (2000). Accumulation of KRM-1648 by Mycobacterium aurum and Mycobacterium tuberculosis. J Antimicrob Chemother 45: 681-684 [Abstract] [Full Text]  
  • Akada, J. K., Shirai, M., Fujii, K., Okita, K., Nakazawa, T. (1999). In Vitro Anti-Helicobacter pylori Activities of New Rifamycin Derivatives, KRM-1648 and KRM-1657. Antimicrob. Agents Chemother. 43: 1072-1076 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»