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 Margolis, P.
Right arrow Articles by Trias, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Margolis, P.
Right arrow Articles by Trias, J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2001, p. 2432-2435, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2432-2435.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Resistance of Streptococcus pneumoniae to Deformylase Inhibitors Is Due to Mutations in defB

Peter Margolis, Corinne Hackbarth, Sara Lopez, Mita Maniar, Wen Wang, Zhengyu Yuan, Richard White, and Joaquim Trias*

Versicor, Inc., Fremont, California 94555

Received 8 January 2001/Returned for modification 23 February 2001/Accepted 29 May 2001

Resistance to peptide deformylase inhibitors in Escherichia coli or Staphylococcus aureus is due to inactivation of transformylase activity. Knockout experiments in Streptococcus pneumoniae R6x indicate that the transformylase (fmt) and deformylase (defB) genes are essential and that a def paralog (defA) is not. Actinonin-resistant mutants of S. pneumoniae ATCC 49619 harbor mutations in defB but not in fmt. Reintroduction of the mutated defB gene into wild-type S. pneumoniae R6x recreates the resistance phenotype. The altered enzyme displays decreased sensitivity to actinonin.

* Corresponding author. Mailing address: Versicor, Inc., 34790 Ardentech Ct., Fremont, CA 94555. Phone: (510) 739-3025. Fax: (510) 739-3003. E-mail: jtrias{at}versicor.com.

Antimicrobial Agents and Chemotherapy, September 2001, p. 2432-2435, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2432-2435.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Duroc, Y., Giglione, C., Meinnel, T. (2009). Mutations in Three Distinct Loci Cause Resistance to Peptide Deformylase Inhibitors in Bacillus subtilis. Antimicrob. Agents Chemother. 53: 1673-1678 [Abstract] [Full Text]  
  • Dean, C. R., Narayan, S., Richards, J., Daigle, D. M., Esterow, S., Leeds, J. A., Kamp, H., Puyang, X., Wiedmann, B., Mueller, D., Voshol, H., van Oostrum, J., Wall, D., Koehn, J., Dzink-Fox, J., Ryder, N. S. (2007). Reduced Susceptibility of Haemophilus influenzae to the Peptide Deformylase Inhibitor LBM415 Can Result from Target Protein Overexpression Due to Amplified Chromosomal def Gene Copy Number. Antimicrob. Agents Chemother. 51: 1004-1010 [Abstract] [Full Text]  
  • Kosowska-Shick, K., Credito, K. L., Pankuch, G. A., DeWasse, B., McGhee, P., Appelbaum, P. C. (2007). Multistep Resistance Selection and Postantibiotic-Effect Studies of the Antipneumococcal Activity of LBM415 Compared to Other Agents. Antimicrob. Agents Chemother. 51: 770-773 [Abstract] [Full Text]  
  • Teo, J. W. P., Thayalan, P., Beer, D., Yap, A. S. L., Nanjundappa, M., Ngew, X., Duraiswamy, J., Liung, S., Dartois, V., Schreiber, M., Hasan, S., Cynamon, M., Ryder, N. S., Yang, X., Weidmann, B., Bracken, K., Dick, T., Mukherjee, K. (2006). Peptide Deformylase Inhibitors as Potent Antimycobacterial Agents. Antimicrob. Agents Chemother. 50: 3665-3673 [Abstract] [Full Text]  
  • Bogdanovich, T., Smith, K. A., Clark, C., Pankuch, G. A., Lin, G., McGhee, P., Dewasse, B., Appelbaum, P. C. (2006). Activity of LBM415 Compared to Those of 11 Other Agents against Haemophilus Species.. Antimicrob. Agents Chemother. 50: 2323-2329 [Abstract] [Full Text]  
  • Nilsson, A. I., Zorzet, A., Kanth, A., Dahlstrom, S., Berg, O. G., Andersson, D. I. (2006). Reducing the fitness cost of antibiotic resistance by amplification of initiator tRNA genes. Proc. Natl. Acad. Sci. USA 103: 6976-6981 [Abstract] [Full Text]  
  • Wang, W., White, R., Yuan, Z. (2006). Proteomic Study of Peptide Deformylase Inhibition in Streptococcus pneumoniae and Staphylococcus aureus.. Antimicrob. Agents Chemother. 50: 1656-1663 [Abstract] [Full Text]  
  • Watters, A. A., Jones, R. N., Leeds, J. A., Denys, G., Sader, H. S., Fritsche, T. R. (2006). Antimicrobial activity of a novel peptide deformylase inhibitor, LBM415, tested against respiratory tract and cutaneous infection pathogens: a global surveillance report (2003-2004). J Antimicrob Chemother 57: 914-923 [Abstract] [Full Text]  
  • Saxena, R., Chakraborti, P. K. (2005). Identification of Regions Involved in Enzymatic Stability of Peptide Deformylase of Mycobacterium tuberculosis. J. Bacteriol. 187: 8216-8220 [Abstract] [Full Text]  
  • Fritsche, T. R., Sader, H. S., Cleeland, R., Jones, R. N. (2005). Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance. Antimicrob. Agents Chemother. 49: 1468-1476 [Abstract] [Full Text]  
  • Steiner-Mosonyi, M., Creuzenet, C., Keates, R. A. B., Strub, B. R., Mangroo, D. (2004). The Pseudomonas aeruginosa Initiation Factor IF-2 Is Responsible for Formylation-independent Protein Initiation in P. aeruginosa. J. Biol. Chem. 279: 52262-52269 [Abstract] [Full Text]  
  • Gil, R., Silva, F. J., Pereto, J., Moya, A. (2004). Determination of the Core of a Minimal Bacterial Gene Set. Microbiol. Mol. Biol. Rev. 68: 518-537 [Abstract] [Full Text]  
  • Jones, R. N., Moet, G. J., Sader, H. S., Fritsche, T. R. (2004). Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates. J Antimicrob Chemother 53: 804-807 [Abstract] [Full Text]  
  • Azoulay-Dupuis, E., Mohler, J., Bedos, J. P. (2004). Efficacy of BB-83698, a Novel Peptide Deformylase Inhibitor, in a Mouse Model of Pneumococcal Pneumonia. Antimicrob. Agents Chemother. 48: 80-85 [Abstract] [Full Text]  
  • Chen, D., Hackbarth, C., Ni, Z. J., Wu, C., Wang, W., Jain, R., He, Y., Bracken, K., Weidmann, B., Patel, D. V., Trias, J., White, R. J., Yuan, Z. (2004). Peptide Deformylase Inhibitors as Antibacterial Agents: Identification of VRC3375, a Proline-3-Alkylsuccinyl Hydroxamate Derivative, by Using an Integrated Combinatorial and Medicinal Chemistry Approach. Antimicrob. Agents Chemother. 48: 250-261 [Abstract] [Full Text]  
  • Serero, A., Giglione, C., Sardini, A., Martinez-Sanz, J., Meinnel, T. (2003). An Unusual Peptide Deformylase Features in the Human Mitochondrial N-terminal Methionine Excision Pathway. J. Biol. Chem. 278: 52953-52963 [Abstract] [Full Text]  
  • Chan, P. F., O'Dwyer, K. M., Palmer, L. M., Ambrad, J. D., Ingraham, K. A., So, C., Lonetto, M. A., Biswas, S., Rosenberg, M., Holmes, D. J., Zalacain, M. (2003). Characterization of a Novel Fucose-Regulated Promoter (PfcsK) Suitable for Gene Essentiality and Antibacterial Mode-of-Action Studies in Streptococcus pneumoniae. J. Bacteriol. 185: 2051-2058 [Abstract] [Full Text]  
  • Hackbarth, C. J., Chen, D. Z., Lewis, J. G., Clark, K., Mangold, J. B., Cramer, J. A., Margolis, P. S., Wang, W., Koehn, J., Wu, C., Lopez, S., Withers, G. III, Gu, H., Dunn, E., Kulathila, R., Pan, S.-H., Porter, W. L., Jacobs, J., Trias, J., Patel, D. V., Weidmann, B., White, R. J., Yuan, Z. (2002). N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity. Antimicrob. Agents Chemother. 46: 2752-2764 [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»