JB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
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 Schujman, G. E.
Right arrow Articles by de Mendoza, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schujman, G. E.
Right arrow Articles by de Mendoza, D.

Journal of Bacteriology, May 2001, p. 3032-3040, Vol. 183, No. 10
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.10.3032-3040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Response of Bacillus subtilis to Cerulenin and Acquisition of Resistance

Gustavo E. Schujman,1 Keum-Hwa Choi,2 Silvia Altabe,1 Charles O. Rock,2,3,* and Diego de Mendoza1

Instituto de Biología Molecular y Celular de Rosario (IBR) and Departamento de Microbiologia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000-Rosario, Argentina1; Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 381052; and Department of Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee 381633

Received 23 October 2000/Accepted 22 February 2001

Cerulenin is a fungal mycotoxin that potently inhibits fatty acid synthesis by covalent modification of the active site thiol of the chain-elongation subtypes of beta -ketoacyl-acyl carrier protein (ACP) synthases. The Bacillus subtilis fabF (yjaY) gene (fabFb) encodes an enzyme that catalyzes the condensation of malonyl-ACP with acyl-ACP to extend the growing acyl chain by two carbons. There were two mechanisms by which B. subtilis adapted to exposure to this antibiotic. First, reporter gene analysis demonstrated that transcription of the operon containing the fabF gene increased eightfold in response to a cerulenin challenge. This response was selective for the inhibition of fatty acid synthesis, since triclosan, an inhibitor of enoyl-ACP reductase, triggered an increase in fabF reporter gene expression while nalidixic acid did not. Second, spontaneous mutants arose that exhibited a 10-fold increase in the MIC of cerulenin. The mutation mapped at the B. subtilis fabF locus, and sequence analysis of the mutant fabF allele showed that a single base change resulted in the synthesis of FabFb[I108F]. The purified FabFb and FabFb[I108F] proteins had similar specific activities with myristoyl-ACP as the substrate. FabFb exhibited a 50% inhibitory concentration (IC50) of cerulenin of 0.1 µM, whereas the IC50 for FabFb[I108] was 50-fold higher (5 µM). These biochemical data explain the absence of an overt growth defect coupled with the cerulenin resistance phenotype of the mutant strain.


* Corresponding author. Mailing address: Biochemistry Department, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794. Phone: (901) 495-3491. Fax: (901) 525-8025. E-mail: charles.rock{at}stjude.org or diegonet{at}citynet.net.ar.


Journal of Bacteriology, May 2001, p. 3032-3040, Vol. 183, No. 10
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.10.3032-3040.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Appl. Environ. Microbiol. Infect. Immun. Eukaryot. Cell
Mol. Cell. Biol. J. Virol. Microbiol. Mol. Biol. Rev.
ALL ASM JOURNALS

Copyright © 2001 by the American Society for Microbiology. All rights reserved.