Chesnel Laurent, Carapito Raphaël, Croizé Jacques, Dideberg Otto, Vernet Thierry, Zapun André
Laboratoire d'Ingénierie des Macromolécules, Institut de Biologie Structurale (CEA/CNRS UMR 5075/UJF), Grenoble, France.
Antimicrob Agents Chemother. 2005 Jul;49(7):2895-902. doi: 10.1128/AAC.49.7.2895-2902.2005.
We have sequenced the penicillin-binding domains of the complete repertoire of penicillin-binding proteins and MurM from 22 clinical isolates of Streptococcus pneumoniae that span a wide range of beta-lactam resistance levels. Evidence of mosaicism was found in the genes encoding PBP 1a, PBP 2b, PBP 2x, MurM, and, possibly, PBP 2a. Five isolates were found to have identical PBP and MurM sequences, even though the MICs for penicillin G ranged from 0.25 to 2.0 mg/liter. When the sequences encoding PBP 1a, PBP 2b, and PBP 2x from one of these isolates were used to transform laboratory strain R6, the resulting strain had a resistance level higher than that of the less resistant isolates carrying that PBP set but lower than that of the most resistant isolates carrying that PBP set. This result demonstrates that if the R6 strain is arbitrarily defined as the standard genotype, some wild genetic backgrounds can either increase or decrease the PBP-based resistance phenotype.
我们对22株肺炎链球菌临床分离株的青霉素结合蛋白和MurM的完整序列中的青霉素结合结构域进行了测序，这些分离株涵盖了广泛的β-内酰胺耐药水平。在编码PBP 1a、PBP 2b、PBP 2x、MurM以及可能还有PBP 2a的基因中发现了镶嵌现象。发现有5株分离株具有相同的PBP和MurM序列，尽管青霉素G的最低抑菌浓度（MIC）范围为0.25至2.0毫克/升。当用其中一株分离株的编码PBP 1a、PBP 2b和PBP 2x的序列转化实验室菌株R6时，所得菌株的耐药水平高于携带该PBP组合的耐药性较低的分离株，但低于携带该PBP组合的耐药性最高的分离株。这一结果表明，如果将R6菌株任意定义为标准基因型，一些野生遗传背景可以增加或降低基于PBP的耐药表型。
