A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139
Tóm tắt
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.
Từ khóa
Tài liệu tham khảo
Albert , M. J. , A. K. Siddique , M. S. Islam , A. S. G. Faruque , M. Ansaruzzaman , S. M. Faruque , and R. B. Sack . 1993 . Large outbreak of clinical cholera due to Vibrio cholerae non-O1 in Bangladesh . Lancet 341 : 704 .
Bik , E. M. , A. E. Bunschoten , R. D. Gouw , and F. Mooi . 1995 . Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis . EMBO J. 14 : 209 - 216 .
Butterton , J. R. , D. T. Beattie , C. L. Gardel , P. A. Carroll , T. Hyman , K. P. Killeen , J. J. Mekalanos , and S. B. Calderwood . 1995 . Heterologous antigen expression in Vibrio cholerae vector strains . Infect. Immun. 63 : 2689 - 2696 .
Calia , K. E. , M. Murtagh , M. J. Ferraro , and S. B. Calderwood . 1994 . Comparison of Vibrio cholerae O139 with V. cholerae O1 classical and El Tor biotypes . Infect. Immun. 62 : 1504 - 1506 .
Cholera Working Group. 1994. Cholera in Bangladesh and Goma Zaire 1994. Presented at the the 30th Joint Conference U.S.-Japan Cooperative Medical Science Program Cholera and Related Diarrheal Diseases Panel Fukuoka Japan 6 to 8 December 1994.
Cholera Working Group . 1993 . Large epidemic of cholera-like disease in Bangladesh caused by Vibrio cholerae O139 synonym Bengal . Lancet 342 : 387 - 390 .
Clewell , D. B. , S. E. Flannagan , and D. Jaworski . 1995 . Unconstrained bacterial promiscuity: the Tn916-Tn1545 family of conjugative transposons . Trends Microbiol. 3 : 229 - 236 .
Comstock , L. E. , D. Maneval , P. Panigrahi , A. Joseph , M. M. Levine , J. B. Kaper , J. G. Morris , and J. Johnson . 1995 . The capsule and O antigen in Vibrio cholerae O139 Bengal are associated with a genetic region not present in Vibrio cholerae O1 . Infect. Immun. 63 : 317 - 323 .
Coster , T. S. , K. P. Killeen , M. K. Waldor , D. Beattie , D. Spriggs , J. R. Kenner , A. Trofa , J. Sadoff , J. J. Mekalanos , and D. N. Taylor . 1995 . Safety, immunogenicity and efficacy of a live attenuated Vibrio cholerae O139 vaccine protype, Bengal-15 . Lancet 345 : 949 - 952 .
Donnenberg , M. S. , and J. B. Kaper . 1991 . Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector . Infect. Immun. 59 : 4310 - 4317 .
Ferro-Novick , S. , M. Honma , and J. Beckwith . 1984 . The product of gene secC is involved in the synthesis of exported proteins in E. coli . Cell 38 : 211 - 217 .
Gerbaud , G. , A. Dodin , F. Goldstein , and P. Courvalin . 1985 . Genetic basis of trimethoprim and O/129 resistance in Vibrio cholerae . Ann. Inst. Pasteur/ Microbiol. (Paris) 136B : 265 - 273 .
Goldberg , I. , and J. J. Mekalanos . 1986 . Effect of a recA mutation on cholera toxin gene amplification and deletion events . J. Bacteriol. 165 : 723 - 731 .
Haider K. D. Beattie M. Waldor J. Mekalanos and K. Killeen. 1995. Unpublished observations.
Herrington , D. A. , R. H. Hall , G. Losonsky , J. J. Mekalanos , R. K. Taylor , and M. M. Levine . 1988 . Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans . J. Exp. Med. 168 : 1487 - 1492 .
Iredell , J. R. , and P. A. Manning . 1994 . Biotype-specific tcpA genes in Vibrio cholerae . FEMS Microbiol. Lett. 121 : 47 - 54 .
Jesudason , M. V. , and T. J. John . 1990 . Transferable trimethoprim resistance of Vibrio cholerae O1 encountered in southern India. Trans. R. Soc. Trop. Med. Hyg. 84 : 137 - 138 .
Karaolis , D. K. , R. Lan , and P. R. Reeves . 1995 . The sixth and seventh cholera pandemics are due to independent clones separately derived from environmental, nontoxigenic, non-O1 Vibrio cholerae . J. Bacteriol. 177 : 3191 - 3198 .
Manning P. A. U. H. Stroeher and R. Morona. 1994. Molecular basis for O-antigen biosynthesis in Vibrio cholerae O1: Ogawa-Inaba switching p. 77-94. In I. K. Wachsmuth P. A. Blake and O. Olsvik (ed.) Vibrio cholerae and cholera: molecular to global perspectives. ASM Press Washington D.C.
Matsushita , S. , Y. Kudoh , and M. Ohashi . 1984 . Transferable resistance to the vibriostatic agent 2,4-diamino-6,7-diisopropyl-pteridine (O/129) in Vibrio cholerae . Microbiol. Immunol. 28 : 1159 - 1162 .
Mekalanos , J. J. 1994 . Live bacterial vaccines: environmental aspects . Curr. Opin. Biotechnol. 5 : 312 - 319 .
Mekalanos , J. J. , and J. C. Sadoff . 1994 . Cholera vaccines: fighting an ancient scourge . Science 265 : 1387 - 1389 .
Mekalanos , J. J. , D. J. Swartz , G. D. Pearson , N. Harford , F. Groyne , and M. deWilde . 1983 . Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development . Nature (London) 306 : 551 - 557 .
Mekalanos , J. J. , M. K. Waldor , C. L. Gardel , T. S. Coster , J. Kenner , K. P. Killeen , D. T. Beattie , A. Trofa , D. N. Taylor , and J. C. Sadoff . 1995 . Live cholera vaccines: perspectives on their construction and safety . Bull. Inst. Pasteur 93 : 255 - 262 .
Miller J. H. 1992. A short course in bacterial genetics. Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y.
Miller , V. L. , and J. J. Mekalanos . 1988 . A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR . J. Bacteriol. 170 : 2575 - 2583 .
Nair , G. B. , P. K. Bag , T. Shimada , T. Ramamurthy , T. Takeda , S. Yamamoto , H. Kurazono , and Y. Takeda . 1995 . Evaluation of DNA probes for specific detection of Vibrio cholerae O139 Bengal . J. Clin. Microbiol. 33 : 2186 - 2187 .
Nair , G. B. , T. Ramamurthy , S. K. Bhattacharya , A. K. Mukhopadhyay , S. Garg , M. K. Bhattacharya , T. Takeda , T. Shimada , Y. Takeda , and B. C. Deb . 1994 . Spread of Vibrio cholerae O139 Bengal in India . J. Infect. Dis. 169 : 1029 - 1034 .
Nair , G. B. , T. Shimada , H. Kurazono , J. Okuda , A. Pal , T. Karasawa , T. Mihara , Y. Uesaka , H. Shirai , S. Garg , P. Saha , A. Mukhopadhyay , T. Ohashi , J. Tada , T. Nakayama , S. Fukushima , T. Takeda , and Y. Takeda . 1994 . Characterization of phenotypic, serological, and toxigenic traits of Vibrio cholerae O139 Bengal . J. Clin. Microbiol. 32 : 2775 - 2779 .
National Committee for Clinical Laboratory Standards. 1990. Performance standards for antimicrobial disk susceptibility tests: approved standard 4th ed. vol. 10. National Committee for Clinical Laboratory Standards Villanova Pa.
Popovic , T. , P. I. Fields , O. Olsvik , J. G. Wells , G. M. Evins , D. N. Cameron , J. J. Farmer , C. A. Bopp , K. Wachsmuth , R. B. Sack , M. J. Albert , G. B. Nair , T. Shimada , and J. C. Feeley . 1995 . Molecular subtyping of toxigenic Vibrio cholerae O139 causing epidemic cholera in India and Bangladesh, 1992-1993 . J. Infect. Dis. 171 : 122 - 127 .
Prager , R. , W. Streckel , R. Stephan , J. Bockemuhl , T. Shimada , and H. Tschape . 1994 . Genomic fingerprinting of Vibrio cholerae O139 from Germany and South Asia in comparison with strains of Vibrio cholerae O1 and other serogroups . Med. Microbiol. Lett. 5 : 217 - 219 .
Ramamurthy , T. , S. Garg , R. Sharma , S. K. Bhattacharya , G. B. Nair , T. Shimada , T. Takeda , T. Karasawa , H. Kurazano , A. Pal , and Y. Takeda . 1993 . Emergence of novel strain of Vibrio cholerae with epidemic potential in southern and eastern India . Lancet 341 : 703 - 704 .
Ramamurthy , T. , A. Pal , S. Pal , and G. B. Nair . 1992 . Taxonomical implications of the emergence of high frequency of occurrence of 2,4-diamino-6,7-diisopropylpteridine-resistant strains of Vibrio cholerae from clinical cases of cholera in Calcutta, India . J. Clin. Microbiol. 30 : 742 - 743 .
Rhine , J. A. , and R. K. Taylor . 1994 . TcpA pilin sequences and colonization requirements for O1 and O139 Vibrio cholerae . Mol. Microbiol. 13 : 1013 - 1020 .
Salyers , A. A. , N. B. Shoemaker , and L. -Y. Li . 1995 . In the driver's seat: the Bacteroides conjugative transposons and the elements they mobilize . J. Bacteriol. 177 : 5727 - 5731 .
Stroeher , U. H. , K. E. Jedani , B. K. Dredge , R. Morona , M. H. Brown , L. E. Karageorgos , M. J. Albert , and P. A. Manning . 1995 . Genetic rearrangements in the rfb regions of Vibrio cholerae O1 and O139 . Proc. Natl. Acad. Sci. USA 84 : 2833 - 2837 .
Tacket , C. O. , G. Losonsky , J. P. Nataro , L. Comstock , J. Michalski , R. Edelman , J. B. Kaper , and M. M. Levine . 1995 . Initial clinical studies of CVD112 Vibrio cholerae O139 live oral vaccine: safety and efficacy against experimental challenge . J. Infect. Dis. 172 : 883 - 886 .
Tschäpe , H. , E. Tietze , and C. Koch . 1981 . Characterization of conjugative R plasmids belonging to the new incompatibility group incU . J. Gen. Microbiol. 127 : 155 - 160 .
Waldor , M. K. , R. Colwell , and J. J. Mekalanos . 1994 . The Vibrio cholerae O139 serogroup antigen includes O-antigen capsule and lipopolysaccharide virulence determinants . Proc. Natl. Acad. Sci. USA 91 : 11388 - 11392 .
Waldor , M. K. , and J. J. Mekalanos . 1994 . Emergence of a new cholera pandemic: molecular analysis of virulence determinants in Vibrio cholerae O139 and development of a live vaccine prototype . J. Infect. Dis. 170 : 278 - 283 .
Waldor , M. K. , and J. J. Mekalanos . 1994 . ToxR regulates virulence gene expression in non-O1 strains of Vibrio cholerae that cause epidemic cholera . Infect. Immun. 62 : 72 - 78 .
Waldor , M. K. , and J. J. Mekalanos . 1994 . Vibrio cholerae O139 specific gene sequences . Lancet 343 : 1366 .
.Waldor M. K. and J. J. Mekalanos. Unpublished data.
Yam , W. - C. , K.-Y. Yuen , S. -S. Wong , and T. -L. Que . 1994 . Vibrio cholerae O139 susceptible to vibriostatic agent O/129 and co-trimoxazole . Lancet 344 : 404 - 405 .
Yamamoto T. G. B. Nair M. J. Albert C. Parodi and Y. Takeda. 1994. In vitro susceptibilities of Vibrio cholerae O1 and O139 to antimicrobial agents and appearance of drug resistance plasmids in Vibrio cholerae O139. Presented at the the 30th Joint Conference U.S.-Japan Cooperative Medical Science Program Cholera and Related Diarrheal Diseases Panel Fukuoka Japan 6 to 8 December 1994.