Penicillin-binding proteins 2x and 2b as primary PBP targets in Streptococcus pneumoniae
Penicillin-binding proteins 2x and 2b as primary PBP targets in Streptococcus pneumoniae
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DOI：
10.1089/mdr.1996.2.183
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Hakenbeck, R
中科院分区：
文献类型：
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作者：
Krauss, J;vanderLinden, M;Hakenbeck, R
与哌拉西林耐药突变体相比，不同的青霉素结合蛋白PBPs在头孢噻肟耐药实验室突变体中受到影响。PBP 2x在头孢噻肟耐药突变体中充当主要PBP靶标，而PBP 2b是哌拉西林耐药突变体中的主要靶标。根据PBP 2x中的突变，它仅作为头孢噻肟的抗性决定因素，或也作为青霉素的抗性决定因素。实验室突变体的PBP 2x中的突变仅在青霉素结合结构域中发现，该结构域包含所有青霉素相互作用酶共有的三个同源框。与耐药性相关的大多数突变发生在SXN或KT/SG盒附近，或在青霉素结合结构域的C末端，类似于实验室突变体的PBP 2b中描述的突变。氨基酸改变也发生在β-内酰胺耐药性临床分离株的PBP 2x中的类似位点，并且这些蛋白质中的大多数也含有具有活性位点丝氨酸的SXXK盒中的变化，提示这些改变可能是临床分离株耐药性发展的关键。
Different penicillin-binding proteins PBPs are affected in cefotaxime-resistant laboratory mutants compared to piperacillin-resistant mutants. PBP2x acts as the primary PBP target in cefotaxime-resistant mutants, whereas PBP2b is the primary target in piperacillin-resistant mutants. Depending on the mutations in PBP2x, it functions as a resistance determinant for cefotaxime only, or for penicillins as well, Mutations in PBP2x of laboratory mutants are found exclusively in the penicillin-binding domain that contains three homology boxes common to all penicillin-interacting enzymes. Most mutations relevant for resistance occur close to the SXN or the KT/SG box, or at the C-terminal end of the penicillin-binding domain, similar to mutations described in PBP2b of laboratory mutants, Amino acid alterations occur at similar sites also in PBP2x of beta-lactam-resistant clinical isolates and most of these proteins also contain changes in the SXXK box with the active site serine, suggesting that these alterations may be critical for resistance development in clinical isolates.