A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139.
Vibrio cholerae O139 is the first non-O1 serogroup of V. cholerae to give rise to epidemic cholera. Apparently, this new serogroup arose from an El Tor O1 strain of V cholerae, but V. cholerae O139 is distinguishable from V. cholerae El Tor O1 by virtue of its novel antigenic structure and also its characteristic pattern of resistances to the antibiotics sulfamethoxazole, trimethoprim, streptomycin, and furazolidone. We found that the first three of these antibiotic resistances are carried on an approximately 62-kb self-transmissible, chromosomally integrating genetic element which we have termed the SXT element. This novel conjugative transposon-like element could be conjugally transferred from V. cholerae O139 to V cholerae O1 and Escherichia coli strains, where it integrated into the recipient chromosomes in a site-specific manner independent of recA. To study the potential virulence properties of the SXT element as well as to improve upon the live attenuated O139 vaccine strain Bengal-2, a large internal deletion in the SXT element was crossed on to the Bengal-2 chromosome. The resulting strain, Bengal-2.SXT(s), is sensitive to sulfamethoxazole and trimethoprim and colonizes the intestines of suckling mice as well as wild-type strains do, suggesting that the SXT element does not encode a colonization factor. Derivatives of Bengal-2.SXT(s) are predicted to be safe, antibiotic-sensitive, live attenuated vaccines for cholera due to the O139 serogroup.
Waldor
M K
MK
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tschäpe
H
H
Mekalanos
J J
JJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002771:Cholera; D022121:Cholera Vaccines / Q000235:genetics; D003227:Conjugation, Genetic; D004251:DNA Transposable Elements / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D018014:Gene Transfer Techniques; D005798:Genes, Bacterial; D008040:Genetic Linkage; D007422:Intestines / Q000382:microbiology; D051379:Mice; D019081:O Antigens; D013045:Species Specificity; D013307:Streptomycin / Q000494:pharmacology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*; D014734:Vibrio cholerae / Q000235:genetics* / Q000472:pathogenicity
D000900:Anti-Bacterial Agents; D022121:Cholera Vaccines; D004251:DNA Transposable Elements; D019081:O Antigens; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013307:Streptomycin