HORIZONTAL TRANSFER OF PENICILLIN-BINDING PROTEIN GENES IN PENICILLIN-RESISTANT CLINICAL ISOLATES OF STREPTOCOCCUS-PNEUMONIAE
HORIZONTAL TRANSFER OF PENICILLIN-BINDING PROTEIN GENES IN PENICILLIN-RESISTANT CLINICAL ISOLATES OF STREPTOCOCCUS-PNEUMONIAE
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DOI：
10.1073/pnas.86.22.8842
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发表时间：
1989-11-01
影响因子：
11.1
通讯作者：
SPRATT, BG
中科院分区：
文献类型：
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作者：
DOWSON, CG;HUTCHISON, A;SPRATT, BG
肺炎链球菌临床分离株对青霉素的耐药性是由于青霉素结合蛋白(PBPs)的改变而产生的，这种蛋白极大地降低了对抗生素的亲和力。我们通过比较6株青霉素敏感株和14株青霉素耐药株PBP2B的转肽酶结构域序列，探讨了青霉素耐药株的来源。此外，我们还对2株敏感株和6株抗性株的淀粉酶基因进行了部分序列测定。所有菌株的淀粉酶基因序列和青霉素敏感菌株的PBP2B基因序列表明，肺炎链球菌在遗传上非常一致。相比之下，青霉素耐药菌株的PBP2B基因显示.apprxeq。14%的序列与青霉素敏感菌株的序列背离，青霉素耐药性的发展涉及到原始PBP2B基因被未知来源的同源基因取代，可能是通过转化。这一遗传事件至少发生过两次，涉及不同的来源，以产生在青霉素耐药肺炎链霉菌株中发现的两类改变的PBP2B基因。耐药株的PBP2B基因有相当大的变异，可能是由于最初引入肺炎链球菌后伴随着错配修复的二次转化事件而引起的。
Resistance to penicillin in clinical isolates of Streptococcus pneumoniae has occurred by the development of altered penicillin-binding proteins (PBPs) that have greatly decreased affinity for the antibiotic. We have investigated the origins of penicillin-resistant strains by comparing the sequences of the transpeptidase domain of PBP2B from 6 penicillin-sensitive and 14 penicillin-resistant strains. In addition we have sequenced part of the amylomaltase gene from 2 of the sensitive and 6 of the resistant strains. The sequences of the amylomaltase gene of all of the strains and of the PBP2B gene of the penicillin-sensitive strains show that S. pneumoniae is genetically very uniform. In contrast the PBP2B genes of the penicillin-resistant strains show .apprxeq. 14% sequence divergence from those of the penicillin-sensitive strains and the development of penicillin resistance has involved the replacement, presumably by transformation, of the original PBP2B gene by a homologous gene from an unknown source. This genetic event has occurred on at least two occasions, invovling different sources, to produce the two classes of altered PBP2B genes found in penicillin-resistant strains of S. pneumoniae. There is considerable variation among the PBP2B genes of the resistant strains that may have arisen by secondary transformation events accompanied by mismatch repair subsequent to their original introductions into S. pneumoniae.