Fermer C, Kristiansen B E, Sköld O, Swedberg G
Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Sweden.
J Bacteriol. 1995 Aug;177(16):4669-75. doi: 10.1128/jb.177.16.4669-4675.1995.
Sulfonamide resistance in Neisseria meningitidis is mediated by altered forms of the chromosomal gene for the drug target enzyme dihydropteroate synthase. Sulfonamides have been used for decades both for prophylaxis and the treatment of meningococcal disease, and resistance is common. Two types of resistance determinants have been identified, and regions important for drug insusceptibility to the corresponding enzyme have been defined by site-directed mutagenesis. Both types of resistance traits have spread among strains of N. meningitidis of different serogroups and serotypes, and the large differences at the nucleotide level in a comparison of the resistance genes with the dhps genes of susceptible meningococci indicate the origin of one or maybe both types in other Neisseria species. One sulfonamide-sensitive strain of N. meningitidis was found to have a mosaic dhps gene with a central part identical to the corresponding part of a gonococcal strain. This observation supports the idea of an interspecies transfer of genetic material in Neisseria species as a mechanism for the development of chromosomally mediated resistance.
脑膜炎奈瑟菌对磺胺类药物的耐药性是由药物靶标酶二氢蝶酸合酶的染色体基因变异形式介导的。磺胺类药物已被用于预防和治疗脑膜炎球菌病数十年,耐药现象很常见。已鉴定出两种类型的耐药决定因素,并且通过定点诱变确定了对相应酶不敏感的重要区域。两种耐药性状都已在不同血清群和血清型的脑膜炎奈瑟菌菌株中传播,与敏感脑膜炎球菌的dhps基因相比,耐药基因在核苷酸水平上的巨大差异表明其中一种或可能两种类型起源于其他奈瑟菌属物种。发现一株对磺胺类药物敏感的脑膜炎奈瑟菌具有镶嵌型dhps基因,其中心部分与淋球菌菌株的相应部分相同。这一观察结果支持了奈瑟菌属物种间遗传物质转移是染色体介导耐药性发展机制的观点。