Maskell J P, Sefton A M, Hall L M
Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, United Kingdom.
Antimicrob Agents Chemother. 1997 Oct;41(10):2121-6. doi: 10.1128/AAC.41.10.2121.
The genetic basis of sulfonamide resistance in six clinical isolates of Streptococcus pneumoniae was demonstrated to be 3- or 6-bp duplications within sulA, the chromosomal gene encoding dihydropteroate synthase. The duplications all result in repetition of one or two amino acids in the region from Arg58 to Tyr63, close to but distinct from the sul-d mutation, a duplication previously reported in a resistant laboratory strain (P. Lopez, M. Espinosa, B. Greenberg, and S. A. Lacks, J. Bacteriol. 169:4320-4326, 1987). Six sulfonamide-susceptible clinical isolates lacked such duplications. The role of the duplications in conferring sulfonamide resistance was confirmed by transforming 319- or 322-bp PCR fragments into the chromosome of a susceptible recipient. Two members of a clone of serotype 9V, one susceptible and one resistant to sulfonamide, which are highly related by other criteria, were shown to have sulA sequences that differ in 7.2% of nucleotides in addition to the duplication responsible for resistance. It is postulated that horizontal gene exchange has been involved in the acquisition (or loss) of resistance within this clone. However, five of the six resistant isolates have distinct duplications and other sequence polymorphisms, suggesting that resistance has arisen independently on many occasions.
已证明肺炎链球菌六个临床分离株中磺胺耐药性的遗传基础是sulA（编码二氢蝶酸合酶的染色体基因）内3或6个碱基对的重复。这些重复均导致在靠近但不同于sul-d突变（先前在一个耐药实验室菌株中报道的重复，P. 洛佩斯、M. 埃斯皮诺萨、B. 格林伯格和S. A. 拉克斯，《细菌学杂志》169:4320 - 4326, 1987）的从精氨酸58到酪氨酸63区域中一个或两个氨基酸的重复。六个磺胺敏感的临床分离株缺乏这种重复。通过将319或322个碱基对的PCR片段转化到一个敏感受体的染色体中，证实了这些重复在赋予磺胺耐药性中的作用。血清型9V的一个克隆中的两个成员，一个对磺胺敏感，一个对磺胺耐药，根据其他标准它们高度相关，结果显示除了导致耐药性的重复外，它们的sulA序列在7.2%的核苷酸上存在差异。据推测，水平基因交换参与了该克隆内耐药性的获得（或丧失）。然而，六个耐药分离株中的五个具有不同的重复和其他序列多态性，这表明耐药性在许多情况下是独立产生的。
