Assuntos
Antibacterianos/história , Propriedade Intelectual , Propriedade , Pesquisa , Estreptomicina/história , Antibacterianos/química , California , Indústria Farmacêutica/economia , Indústria Farmacêutica/legislação & jurisprudência , História do Século XX , Humanos , Relações Interpessoais , New Jersey , Prêmio Nobel , Propriedade/legislação & jurisprudência , Patentes como Assunto/legislação & jurisprudência , Pesquisa/legislação & jurisprudência , Estreptomicina/químicaRESUMO
A total of 254 isolates of Campylobacter jejuni and three isolates of Campylobacter coli, isolated from Sweden, Canada, and Egypt, were screened for kanamycin resistance. Eight strains of C. jejuni contained large plasmids that carried the aphA-3 kanamycin-resistance marker. In six plasmids, the aphA-3 gene was located downstream of an apparent insertion sequence, designated IS607*, which showed a considerable similarity to IS607, characterized on the chromosome of some Helicobacter pylori strains. In contrast, the other plasmids carried the aphA-3 gene as a part of a resistance cluster. This included three resistance markers encoding 6'-adenylyltransferase (aadE), streptothricin acetyltransferase (sat), and 3'-aminoglycoside phosphotransferase type III (aphA-3). The genetic organization of this resistance cluster suggests that it has been acquired by C. jejuni from a Gram-positive organism. The IS607* element was also observed in kanamycin-susceptible strains of C. jejuni on plasmids mediating tetracycline resistance. The kanamycin-resistance phenotype transferred along with tetracycline resistance by conjugation from four representative C. jejuni strains to a recipient strain of C. jejuni. The kanamycin-resistance determinant (aphA-3) was stably transferred from one of the four C. jejuni strains to a recipient strain of Escherichia coli. However, the C. jejuni plasmid, which also carries the tetO gene, was not maintained in E. coli. Pulsed-field gel electrophoresis revealed the integration of approximately 50 kb of the plasmid into the chromosome of the E. coli recipient.
Assuntos
Campylobacter jejuni/genética , Resistência a Canamicina/genética , Plasmídeos/genética , Sequência de Bases , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/isolamento & purificação , Canadá , Primers do DNA , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Egito , Microbiologia de Alimentos , Geografia , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Mapeamento por Restrição , SuéciaRESUMO
Sulfonamides were the first drugs acting selectively on bacteria which could be used systemically. Today they are infrequently used, in part due to widespread resistance. The target of sulfonamides, and the basis for their selectivity, is the enzyme dihydropteroate synthase (DHPS) in the folic acid pathway. Mammalian cells are not dependent on endogenous synthesis of folic acid and generally lack DHPS. Instead, they have a folate uptake system which most prokaryotes lack. Laboratory mutants in the dhps (folP) gene can be easily isolated and show a trade off between sulfonamide resistance and DHPS enzyme performance. Clinical resistant mutants, however, have additional compensatory mutations in DHPS that allow it to function normally. In many pathogenic bacteria sulfonamide resistance is mediated by the horizontal transfer of foreign folP or parts of it. Clinical resistance in gram-negative enteric bacteria is plasmid-borne and is effected by genes encoding alternative drug-resistance variants of the DHPS enzymes. Two such genes, sul1 and sul2, have been sequenced and are found at roughly the same frequency among clinical isolates. Remarkably, the corresponding DHPS enzymes show pronounced insensitivity to sulfonamides but normal binding to the p -aminobenzoic acid substrate, despite the close structural similarity between substrate and inhibitor. Copyright 2000 Harcourt Publishers Ltd.
