Skip Navigation



JAC Advance Access published online on May 18, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh256
© 2004 by The British Society for Antimicrobial Chemotherapy
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
54/1/100    most recent
dkh256v1
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 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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Diniz, C. G.
Right arrow Articles by Jeffrey Smith, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Diniz, C. G.
Right arrow Articles by Jeffrey Smith, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received January 18, 2004
Revised March 29, 2004
Accepted April 4, 2004

Original article

Differential gene expression in a Bacteroides fragilis metronidazole-resistant mutant

Claudio Galuppo Diniz 1, Luiz M. Farias 2*, Maria Auxiliadora R. Carvalho 2, Edson R. Rocha 3, C. Jeffrey Smith 3

1 Department of Microbiology and Immunology, The Brody School of Medicine, East Carolina University, Greenville, NC, USA; Departamento de Microbiologia, ICB-UFMG, Belo Horizonte, MG, Brazil
2 Departamento de Microbiologia, ICB-UFMG, Belo Horizonte, MG, Brazil
3 Department of Microbiology and Immunology, The Brody School of Medicine, East Carolina University, Greenville, NC, USA

* To whom correspondence should be addressed. E-mail: macedo{at}icb.ufmg.br.


  Abstract

Objectives: The current work focused on molecular changes in a spontaneous Bacteroides fragilismutant selected by low concentrations of metronidazole as an adaptive response to the drug.

Methods: A metronidazole-resistant strain derived from B. fragilis ATCC 25285 was selected by passage in the presence of drug using 0-4 mg/L gradient plates. Using a combination of proteomics for identification of differentially expressed proteins by two-dimensional electrophoresis and selected mutational analyses by single cross-over insertion and an allelic exchange, we have identified genes involved in the adaptive response to metronidazole.

Results: There are significant changes in the protein profiles of resistant strains. These changes appeared to affect a wide range of metabolic proteins including lactate dehydrogenase (up-regulated) and flavodoxin (down-regulated), which may be involved in electron transfer reactions. Also, the enzymic activity of the pyruvate-ferredoxin oxidoreductase (PorA) complex was impaired. Mutant strains lacking the genes for flavodoxin and PorA were less susceptible to metronidazole than the sensitive parent, and a double flavodoxin/PorA mutant had even less susceptibility but none of the mutants were as resistant as the spontaneous metronidazole-resistant strain.

Conclusions: Overall, the data indicated that there were global changes in the regulation of the physiology of the metronidazole-resistant strain. In addition, flavodoxin was identified as an important contributor to metronidazole sensitivity in B. fragilis.

Key Words: Keywords: proteomics, anaerobes, drug resistance


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
 Clin. Microbiol. Rev.Home page
H. M. Wexler
Bacteroides: the Good, the Bad, and the Nitty-Gritty
Clin. Microbiol. Rev., October 1, 2007; 20(4): 593 - 621.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
A. Katsandri, J. Papaparaskevas, A. Pantazatou, G. L. Petrikkos, G. Thomopoulos, D. P. Houhoula, and A. Avlamis
Two Cases of Infections Due to Multidrug-Resistant Bacteroides fragilis Group Strains.
J. Clin. Microbiol., September 1, 2006; 44(9): 3465 - 3467.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
A. Katsandri, A. Avlamis, A. Pantazatou, D. P. Houhoula, and J. Papaparaskevas
Dissemination of nim-class genes, encoding nitroimidazole resistance, among different species of Gram-negative anaerobic bacteria isolated in Athens, Greece
J. Antimicrob. Chemother., September 1, 2006; 58(3): 705 - 706.
[Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
J. Soki, M. Gal, J. S. Brazier, V. O. Rotimi, E. Urban, E. Nagy, and B. I. Duerden
Molecular investigation of genetic elements contributing to metronidazole resistance in Bacteroides strains
J. Antimicrob. Chemother., February 1, 2006; 57(2): 212 - 220.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Microbiol.Home page
F. Mory, J.-P. Carlier, C. Alauzet, M. Thouvenin, H. Schuhmacher, and A. Lozniewski
Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain
J. Clin. Microbiol., October 1, 2005; 43(10): 5380 - 5383.
[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.