A BIOLOGICAL PRICE OF ANTIBIOTIC-RESISTANCE - MAJOR CHANGES IN THE PEPTIDOGLYCAN STRUCTURE OF PENICILLIN-RESISTANT PNEUMOCOCCI
A BIOLOGICAL PRICE OF ANTIBIOTIC-RESISTANCE - MAJOR CHANGES IN THE PEPTIDOGLYCAN STRUCTURE OF PENICILLIN-RESISTANT PNEUMOCOCCI
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DOI：
10.1073/pnas.87.14.5415
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发表时间：
1990-07-01
影响因子：
11.1
通讯作者：
TOMASZ, A
中科院分区：
文献类型：
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作者：
GARCIABUSTOS, J;TOMASZ, A
肺炎球菌菌株对青霉素的耐药性水平大大提高，目前已在世界范围内越来越频繁地被描述。这些菌株的抗生素耐药性机制涉及细胞壁合成酶（青霉素结合蛋白）的分子重塑。我们现在已经分析了10个青霉素敏感和10个青霉素耐药的临床分离株（4个中间和6个高水平的电阻）与高分辨率HPLC技术的肽聚糖结构。敏感菌株的细胞壁肽聚糖含有单体和寡聚体形式的主要（70%或更多）线性茎肽，其序列为L-Ala-D-iGln-L-Lys-D-Ala（其中iGln是异谷氨酰胺）。相反，抗性细胞壁的主要肽种类（70%或更多）是在ε-丝氨酸上携带Ala-Ser或Ala-Ala二肽的异常分支茎肽。茎肽赖氨酸残基的氨基。在肽聚糖的结构改变是不相关的血清型，日期，或网站的分离，但表现出很强的相关性与青霉素耐药性，并与高水平的青霉素耐药性，并在遗传转化过程中与高水平的青霉素耐药性共转化。我们认为，青霉素结合蛋白的活性位点在耐药细菌，这导致在青霉素的亲和力降低的重塑，也改变了这些酶的底物偏好更疏水的支链肽（而不是线性肽）的细胞壁合成。
Pneumococcal strains were greatly elevated levels of resistance to penicillin have by now been described with increasing frequency worldwide. The mechanism of antibiotic resistance in these strains involves the molecular remodeling of cell wall synthetic enzymes (penicillin binding proteins). We have now analyzed the peptidoglycan structures of 10 penicillin-susceptible and 10 penicillin-resistant clinical isolates (4 of intermediate and 6 of high level resistance) with a high-resolution HPLC technique. Cell wall peptidoglycan of the susceptible strains contained monomeric and oligomeric forms of primarily (70% or more) linear stem peptides with the sequence of L-Ala-D-iGln-L-Lys-D-Ala (where iGln is isoglutamine). In contrast, the major peptide species (70% or more) of resistant cell walls were abnormal branched-stem peptides carrying Ala-Ser or Ala-Ala dipeptides on the .epsilon.-amino groups of the stem peptide lysine residues. The structural alteration in the peptidoglycan was not related to serotype, date, or site of isolation but showed strong correlation with penicillin resistance and was cotransformed with high-level penicilln resistance and was cotransformed with high-level penicillin resistance during genetic transformation. We suggest that the remodeling of the active site of penicillin binding proteins in the resistant bacteria, which results in the reduced affinity for penicillin, also changes the substrate preference of these enzymes for the more hydrophobic branched peptides (instead of linear peptides) for cell wall synthesis.