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 Google Scholar
Google Scholar
Right arrow Articles by Kalia, V.
Right arrow Articles by Raj, V. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kalia, V.
Right arrow Articles by Raj, V. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2009, p. 1427-1433, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.00887-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mode of Action of Ranbezolid against Staphylococci and Structural Modeling Studies of Its Interaction with Ribosomes{triangledown}

Vandana Kalia,1 Rajni Miglani,2 Kedar P. Purnapatre,1 Tarun Mathur,1 Smita Singhal,1 Seema Khan,1 Sreedhara R. Voleti,2,{dagger} Dilip J. Upadhyay,1 Kulvinder Singh Saini,3 Ashok Rattan,4 and V. Samuel Raj1*

Department of Infectious Diseases,1 Department of Molecular Modeling,2 Department of Biotechnology, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Sector-18, Gurgaon 122 015, India,3 SRL Ranbaxy, Sector-18, Gurgaon 122 015, India4

Received 6 July 2008/ Returned for modification 18 September 2008/ Accepted 9 December 2008

Oxazolidinones are known to inhibit protein biosynthesis and act against a wide spectrum of gram-positive bacteria. A new investigational oxazolidinone, ranbezolid, inhibited bacterial protein synthesis in Staphylococcus aureus and Staphylococcus epidermidis. In S. epidermidis, ranbezolid showed inhibition of cell wall and lipid synthesis and a dose-dependent effect on membrane integrity. A kill-kinetics study showed that ranbezolid was bactericidal against S. epidermidis. In vitro translation of the luciferase gene done using bacterial and mammalian ribosomes indicated that ranbezolid specifically inhibited the bacterial ribosome. Molecular modeling studies revealed that both linezolid and ranbezolid fit in similar manners the active site of ribosomes, with total scores, i.e., theoretical binding affinities after consensus, of 5.2 and 6.9, respectively. The nitrofuran ring in ranbezolid is extended toward C2507, G2583, and U2584, and the nitro group forms a hydrogen bond from the base of G2583. The interaction of ranbezolid with the bacterial ribosomes clearly helps to elucidate its potent activity against the target pathogen.

* Corresponding author. Mailing address: Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Sector-18, Gurgaon 122 015, India. Phone: 91 124 2342001, ext. 5237. Fax: 91 124 2343544. E-mail: samuel.raj{at}ranbaxy.com

{triangledown} Published ahead of print on 15 December 2008.

{dagger} Present address: Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 040, India.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1427-1433, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.00887-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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