Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 3 June 2005:
Vol. 308. no. 5727, pp. 1480 - 1483
DOI: 10.1126/science.1110699
Prev | Table of Contents | Next

Reports

A Fluoroquinolone Resistance Protein from Mycobacterium tuberculosis That Mimics DNA

Subray S. Hegde,1* Matthew W. Vetting,1* Steven L. Roderick,1 Lesley A. Mitchenall,2 Anthony Maxwell,2 Howard E. Takiff,3 John S. Blanchard1{dagger}

Fluoroquinolones are gaining increasing importance in the treatment of tuberculosis. The expression of MfpA, a member of the pentapeptide repeat family of proteins from Mycobacterium tuberculosis, causes resistance to ciprofloxacin and sparfloxacin. This protein binds to DNA gyrase and inhibits its activity. Its three-dimensional structure reveals a fold, which we have named the right-handed quadrilateral ß helix, that exhibits size, shape, and electrostatic similarity to B-form DNA. This represents a form of DNA mimicry and explains both its inhibitory effect on DNA gyrase and fluoroquinolone resistance resulting from the protein's expression in vivo.

1 Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
2 Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK.
3 Laboratorio de Genética Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas 1020A, Venezuela.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: blanchar{at}aecom.yu.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in Vietnam.
D. D. An, N. T. Hong Duyen, N. T. N. Lan, D. V. Hoa, D. T. M. Ha, V. S. Kiet, D. D. A. Thu, N. Van Vinh Chau, N. H. Dung, D. N. Sy, et al. (2009)
Antimicrob. Agents Chemother. 53, 4835-4839
   Abstract »    Full Text »    PDF »
Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat.
J. Strahilevitz, G. A. Jacoby, D. C. Hooper, and A. Robicsek (2009)
Clin. Microbiol. Rev. 22, 664-689
   Abstract »    Full Text »    PDF »
Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance.
S. A. McMahon, G. A. Roberts, K. A. Johnson, L. P. Cooper, H. Liu, J. H. White, L. G. Carter, B. Sanghvi, M. Oke, M. D. Walkinshaw, et al. (2009)
Nucleic Acids Res. 37, 4887-4897
   Abstract »    Full Text »    PDF »
Mutational analysis of quinolone resistance in the plasmid-encoded pentapeptide repeat proteins QnrA, QnrB and QnrS.
J. M. Rodriguez-Martinez, A. Briales, C. Velasco, M. C. Conejo, L. Martinez-Martinez, and A. Pascual (2009)
J. Antimicrob. Chemother. 63, 1128-1134
   Abstract »    Full Text »    PDF »
The Pentapeptide Repeat Proteins MfpAMt and QnrB4 Exhibit Opposite Effects on DNA Gyrase Catalytic Reactions and on the Ternary Gyrase-DNA-Quinolone Complex.
A. Merens, S. Matrat, A. Aubry, C. Lascols, V. Jarlier, C.-J. Soussy, J.-D. Cavallo, and E. Cambau (2009)
J. Bacteriol. 191, 1587-1594
   Abstract »    Full Text »    PDF »
Solution Structure and Refolding of the Mycobacterium tuberculosis Pentapeptide Repeat Protein MfpA.
S. Khrapunov, H. Cheng, S. Hegde, J. Blanchard, and M. Brenowitz (2008)
J. Biol. Chem. 283, 36290-36299
   Abstract »    Full Text »    PDF »
YacG from Escherichia coli is a specific endogenous inhibitor of DNA gyrase.
S. Sengupta and V. Nagaraja (2008)
Nucleic Acids Res. 36, 4310-4316
   Abstract »    Full Text »    PDF »
The Structure of the Haemophilus influenzae HMW1 Pro-piece Reveals a Structural Domain Essential for Bacterial Two-partner Secretion.
H.-J. Yeo, T. Yokoyama, K. Walkiewicz, Y. Kim, S. Grass, and J. W. St. Geme III (2007)
J. Biol. Chem. 282, 31076-31084
   Abstract »    Full Text »    PDF »
Role of a qnr-Like Gene in the Intrinsic Resistance of Enterococcus faecalis to Fluoroquinolones.
S. Arsene and R. Leclercq (2007)
Antimicrob. Agents Chemother. 51, 3254-3258
   Abstract »    Full Text »    PDF »
Protein p56 from the Bacillus subtilis phage {phi}29 inhibits DNA-binding ability of uracil-DNA glycosylase.
G. Serrano-Heras, J. A. Ruiz-Maso, G. d. Solar, M. Espinosa, A. Bravo, and M. Salas (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
The Phytotoxin Albicidin is a Novel Inhibitor of DNA Gyrase.
S. M. Hashimi, M. K. Wall, A. B. Smith, A. Maxwell, and R. G. Birch (2007)
Antimicrob. Agents Chemother. 51, 181-187
   Abstract »    Full Text »    PDF »
Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding.
S. Sengupta, M. Shah, and V. Nagaraja (2006)
Nucleic Acids Res. 34, 5567-5576
   Abstract »    Full Text »    PDF »
Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy.
D. F. Warner and V. Mizrahi (2006)
Clin. Microbiol. Rev. 19, 558-570
   Abstract »    Full Text »    PDF »
qnrB, Another Plasmid-Mediated Gene for Quinolone Resistance..
G. A. Jacoby, K. E. Walsh, D. M. Mills, V. J. Walker, H. Oh, A. Robicsek, and D. C. Hooper (2006)
Antimicrob. Agents Chemother. 50, 1178-1182
   Abstract »    Full Text »    PDF »
An elongated spine of buried core residues necessary for in vivo folding of the parallel beta-helix of P22 tailspike adhesin.
R. Simkovsky and J. King (2006)
PNAS 103, 3575-3580
   Abstract »    Full Text »    PDF »
New Mechanism of Fluoroquinolone Resistance in TB.
(2005)
Journal Watch Infectious Diseases 2005, 10
   Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)