Skip Navigation


JAC Advance Access originally published online on June 9, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
54/1/90    most recent
dkh294v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Bast, D. J.
Right arrow Articles by Rubinstein, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bast, D. J.
Right arrow Articles by Rubinstein, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of Antimicrobial Chemotherapy 2004 54(1):90-94; doi:10.1093/jac/dkh294
JAC vol.54 no.1 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

Type II topoisomerase mutations in Bacillus anthracis associated with high-level fluoroquinolone resistance

Darrin J. Bast1,2,*, Abed Athamna3, Carla L. Duncan1, Joyce C. S. de Azavedo1,2, Donald E. Low1,2, Galia Rahav4, David Farrell5 and Ethan Rubinstein4

1 Toronto Centre for Antimicrobial Research and Evaluation (ToCARE), Room 1483, Department of Microbiology, Mount Sinai Hospital, 600 University Avenue, Toronto; 2 Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; 3 Triangle Research and Development Center, Kfar Quara, Israel; 4 The Infectious Diseases Unit, Sheba Medical Center, Tel Aviv University School of Medicine, Tel Hashomer, Israel; 5 GR Micro Ltd., London, UK

* Corresponding author. Tel: +1-416-586-3207; Fax: +1-416-586-8746; Email: dbast{at}mtsinai.on.ca

Objectives: To identify and characterize the mechanisms of high-level fluoroquinolone resistance in two strains of Bacillus anthracis following serial passage in increasing concentrations of fluoroquinolones.

Methods: Fluoroquinolone-resistant isolates of the Sterne and Russian Anthrax Vaccine STi strains were obtained following serial passage in the presence of increasing concentrations of four different fluoroquinolones. The quinolone-resistance-determining regions of the type II topoisomerase genes from the resistant strains were amplified by PCR and characterized by DNA sequence analysis. The MICs in the presence and absence of reserpine were determined using broth microdilution as a means of detecting active efflux.

Results: Single and double amino acid substitutions in the GyrA (Ser-85-Leu; Glu-89-Arg/Gly/Lys) and GrlA (Ser-81-Tyr; Val-96-Ala; Asn-70-Lys) were most common. A single amino acid substitution in GyrB (Asp-430-Asn) was also identified. Efflux only applied to isolates selected for by either levofloxacin or ofloxacin.

Conclusions: Specific amino acid substitutions in the type II topoisomerase enzymes significantly contributed to the development of high-level fluoroquinolone resistance in B. anthracis. However, notable differences between the strains and the drugs tested were identified including the role of efflux and the numbers and types of mutations identified.

Keywords: anthrax , DNA gyrase , topoisomerase IV


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
V. A. Luna, D. S. King, J. Gulledge, A. C. Cannons, P. T. Amuso, and J. Cattani
Susceptibility of Bacillus anthracis, Bacillus cereus, Bacillus mycoides, Bacillus pseudomycoides and Bacillus thuringiensis to 24 antimicrobials using Sensititre(R) automated microbroth dilution and Etest(R) agar gradient diffusion methods
J. Antimicrob. Chemother., September 1, 2007; 60(3): 555 - 567.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
K. Poole
Efflux-mediated antimicrobial resistance
J. Antimicrob. Chemother., July 1, 2005; 56(1): 20 - 51.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.