Waldor M K, Tschäpe H, Mekalanos J J
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Bacteriol. 1996 Jul;178(14):4157-65. doi: 10.1128/jb.178.14.4157-4165.1996.
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.
霍乱弧菌O139是首个引发霍乱流行的非O1血清群霍乱弧菌。显然，这个新血清群源自霍乱弧菌的一株埃尔托O1菌株，但霍乱弧菌O139因其新颖的抗原结构以及对磺胺甲恶唑、甲氧苄啶、链霉素和呋喃唑酮的独特耐药模式，与霍乱弧菌埃尔托O1有所不同。我们发现，前三种抗生素耐药性由一个约62 kb的可自我传递、整合到染色体上的遗传元件携带，我们将其命名为SXT元件。这个新颖的接合转座子样元件可通过接合作用从霍乱弧菌O139转移至霍乱弧菌O1和大肠杆菌菌株，并以一种不依赖recA的位点特异性方式整合到受体染色体中。为了研究SXT元件的潜在毒力特性，以及改进减毒活疫苗菌株O139孟加拉-2，我们将SXT元件中的一个大的内部缺失转移到了孟加拉-2染色体上。所得菌株孟加拉-2.SXT(s)对磺胺甲恶唑和甲氧苄啶敏感，并且与野生型菌株一样能在乳鼠肠道中定殖，这表明SXT元件不编码定殖因子。由于O139血清群的原因，预计孟加拉-2.SXT(s)的衍生物是安全、对抗生素敏感的霍乱减毒活疫苗。
