Mosaic pbpX genes of major clones of penicillin‐resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin‐sensitive Streptococcus oralis

Mosaic pbpX genes of major clones of penicillin‐resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin‐sensitive Streptococcus oralis
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耐青霉素肺炎链球菌主要克隆的镶嵌 pbpX 基因是由青霉素敏感口腔链球菌的 pbpX 基因进化而来

DOI:
10.1111/j.1365-2958.1994.tb01089.x
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发表时间:
1994
影响因子:
3.6
通讯作者:
R. Hakenbeck
R. Hakenbeck
中科院分区:
生物学2区
文献类型:
--
作者:
C. Sibold;J. Henrichsen;A. König;Christian Martín;L. Chalkley;R. Hakenbeck

文献摘要

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青霉素耐药肺炎链球菌临床分离株含有青霉素结合蛋白嵌合体基因,其编码的青霉素结合蛋白对β-内酰胺类抗生素的亲和力降低。这些嵌合体被认为是来自相关青霉素耐药物种的同源PBP基因转移的结果。我们现在已经在来自南非的一株青霉素敏感的口腔链球菌M3中发现了一个与肺炎球菌pbpx基因(PbpX)同源的基因,该基因与青霉素敏感的肺炎球菌的pbpX基因有近20%的差异,以及轻型链球菌NCTC 10712株的嵌合型pbpX基因的一个中心序列块。相比之下,三个遗传上不相关的青霉素耐药肺炎链球菌的pbpX基因1-1.5kb嵌合块的差异只有2%-4%,其中两个代表了6B和23F血清型的克隆,这两个克隆在西班牙流行,在其他国家也已经发现。在低浓度的头孢噻肟作用下,可以从NCTC 10712或口腔葡萄球菌M3中选择含有pbpX基因的肺炎链球菌R6敏感株的转化子,这表明β敏感的内酰胺类菌株之间已经发生了基因交换。这些数据与以下假设是一致的,即作为青霉素耐药决定因素的多溴联苯是通过敏感共生物种基因点突变的积累而进化的。
Penicillin‐resistant clinical isolates of Streptococcus pneumoniae contain mosaic penicillin‐binding protein (PBP) genes that encode PBPs with decreased affinity for β‐lactam antibiotics. The mosaic blocks are believed to be the result of gene transfer of homologous PBP genes from related penicillin‐resistant species. We have now identified a gene homologous to the pneumococcal PBP2x gene (pbpX) in a penicillin‐sensitive Streptococcus oralis isolate M3 from South Africa that diverged by almost 20% from pbpX of penicillin‐sensitive pneumococci, and a central sequence block of a mosaic pbpX gene of Streptococcus mitis strain NCTC 10712. In contrast, it differed by only 2‐4% of the 1 to 1.5 kb mosaic block in pbpX genes of three genetically unrelated penicillin‐resistant S. pneumoniae isolates, two of them representing clones of serotype 6B and 23F, which are prevalent in Spain and are also already found in other countries. With low concentrations of cefotaxime, transformants of the sensitive S. pneumoniae R6 strain could be selected containing pbpX genes from either S. mitis NCTC 10712 or S. oralis M3, demonstrating that genetic exchange can already occur between β‐lactam‐sensitive species. These data are in agreement with the assumption that PBPs as penicillin‐resistance determinants have evolved by the accumulation of point mutations in genes of sensitive commensal species.