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Antimicrobial Agents and Chemotherapy, November 2001, p. 2991-3000, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.2991-3000.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Molecular Analysis of Antibiotic Resistance Gene Clusters in Vibrio cholerae O139 and O1 SXT Constins

Bianca Hochhut,1 Yasmin Lotfi,1 Didier Mazel,2 Shah M. Faruque,3 Roger Woodgate,4 and Matthew K. Waldor1,*

Division of Geographic Medicine/Infectious Diseases, New England Medical Center, Tufts University School of Medicine, and Howard Hughes Medical Institute, Boston, Massachusetts 021111; Unité de Programmation Moléculaire et Toxicologie Génétique, Institut Pasteur, 75724 Paris Cedex 15, France2; Molecular Genetics Laboratory, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka-1000, Bangladesh3; and Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 208924

Received 16 May 2001/Returned for modification 11 July 2001/Accepted 30 July 2001

Many recent Asian clinical Vibrio cholerae E1 Tor O1 and O139 isolates are resistant to the antibiotics sulfamethoxazole (Su), trimethoprim (Tm), chloramphenicol (Cm), and streptomycin (Sm). The corresponding resistance genes are located on large conjugative elements (SXT constins) that are integrated into prfC on the V. cholerae chromosome. We determined the DNA sequences of the antibiotic resistance genes in the SXT constin in MO10, an O139 isolate. In SXTMO10, these genes are clustered within a composite transposon-like structure found near the element's 5' end. The genes conferring resistance to Cm (floR), Su (sulII), and Sm (strA and strB) correspond to previously described genes, whereas the gene conferring resistance to Tm, designated dfr18, is novel. In some other O139 isolates the antibiotic resistance gene cluster was found to be deleted from the SXT-related constin. The El Tor O1 SXT constin, SXTET, does not contain the same resistance genes as SXTMO10. In this constin, the Tm resistance determinant was located nearly 70 kbp away from the other resistance genes and found in a novel type of integron that constitutes a fourth class of resistance integrons. These studies indicate that there is considerable flux in the antibiotic resistance genes found in the SXT family of constins and point to a model for the evolution of these related mobile elements.

* Corresponding author. Mailing address: Division of Geographic Medicine/Infectious Diseases, New England Medical Center and Tufts University School of Medicine, Box 041, 750 Washington St., Boston, MA 02111. Phone: (617) 636 7618. Fax: (617) 636 5292. E-mail: mwaldor{at}lifespan.org.

Antimicrobial Agents and Chemotherapy, November 2001, p. 2991-3000, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.2991-3000.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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