Many clinical isolates of the human pathogen contain conjugative plasmids. and subfamilies. The determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The 923287-50-7 IC50 current presence of 923287-50-7 IC50 the toxin and antitoxin on different plasmids might clarify why the sponsor selection of this IncP1 plasmid is bound to species. The isolated plasmids conjugated between strains effectively, but didn’t enhance transfer of the hereditary marker. Intro The obligate human being pathogen colonizes mucosal cells in the urogenital tracts to trigger the std gonorrhea . Although gonorrhea can still be treated with antibiotics it has progressively accumulated resistance against many antibiotics like e.g. penicillin, ciprofloxacin, tetracycline, azithromycin and 923287-50-7 IC50 cefixime, and currently not many new antibiotics are available . The rapid spread of antibiotic resistance is caused by the high rate of horizontal gene transfer in is driven by its high rates of natural transformation and recombination. DNA for horizontal gene transfer is most likely derived from lysis, but transfer frequencies are approximately 500 fold increased in strains which secrete DNA via the Type IV secretion system found within the recently characterized Gonococcal Genetic Island (GGI) . Horizontal gene transfer also occurs via conjugative plasmids, which can not only transfer their own DNA, but often can also co-mobilize chromosomal or plasmid DNA. Currently three types of gonoccocal conjugative plasmids have been described in determinant . The 24.5 MDa plasmid (also called pLE2451) was first found in 1974 in the United States in clinical isolates of non-penicillinase and penicillinase producing , , . The host range of the 24.5 MDa plasmid 923287-50-7 IC50 is limited to and to some strains of . The 24.5 MDa plasmid was shown not to be involved in the mobilization of genomic DNA. In 1982, 25.2 MDa conjugative plasmids containing determinants were identified in clinical isolates from the United States . determinants are transposon-borne determinants found in many organisms like e.g., , , , spp  and ,  and are responsible for high levels of tetracycline resistance. The determinants within the 25.2 MDa plasmids are derived from a so-called 923287-50-7 IC50 class II Tn916-like transposon insertion which means that large parts of the Tn916-like transposon are deleted but that the determinant is maintained . Nowadays, gonoccocal isolates resistant to high doses of tetracycline (MIC>8 g/ml) carrying 25.2 MDa plasmids have been isolated worldwide , , , . Restriction endonuclease mapping and Southern blotting of conjugative plasmids from different isolates revealed two different 25.2 MDa conjugative plasmids , which were named the American and Dutch type plasmids . The restriction map of the Dutch type plasmid strongly resembled the restriction map of the 24.5 MDa conjugative plasmid and it was proposed that the Dutch type 25.2 MDa plasmid is a derivative of the 24.5 MDa plasmid by an insertion of the determinant , . Early studies proposed that the American type plasmid might be similar to both the conjugative and the Dutch type plasmid in areas of conserved functions like replication, incompatibility and transfer function , but restriction endonuclease mapping demonstrated large differences between American and Dutch type plasmids . Sequencing of the regions of American and Dutch type plasmids also revealed differences within the two determinants, and it was proposed that the determinant found in the American type conjugative plasmids has a different origin from the F2rl1 determinant present in the Dutch type conjugative plasmids . In a different study 13 American determinants were linked to the restriction maps of American type conjugative plasmids . Based on the different sequences PCR primers were developed which could differentiate between the 2 different determinants. The determinant has been generally linked to the conjugation plasmid type, although some determinants have also been identified in plasmids with restriction.