肺炎链球菌青霉素MIC与PBP变异的关系  

THE RELATION BETWEEN MINIMAL INHIBITORY CONCENTRATION OF PENICILLIN AND PENICILLIN-BINDING PROTEIN MUTATIONS OF STREPTOCOCCUS PNEUMONIAE

作　　者：黄卫青[1] 赵自云[1] 邓华[1] 

机构地区：[1]青岛大学医学院第二附属医院检验科,山东青岛266042

出　　处：《青岛大学医学院学报》2011年第2期153-155,共3页Acta Academiae Medicinae Qingdao Universitatis

摘　　要：目的探讨肺炎链球菌(Sp)青霉素抗生素最小抑菌质量浓度(MIC)与青霉素结合蛋白(PBP)1A、2B和2X变异的关系。方法用MIC法对51株Sp进行青霉素药敏试验,并提取每株Sp的DNA,分别对其PBP1A、PBP2B中编码青霉素结合区域进行PCR扩增然后测序,并用软件进行序列比对,分析PBP1A、2B保守序列的氨基酸置换。结果在所有MIC≤1 mg/L的青霉素敏感Sp(PSSP)中均未发现PBP1A突变,而在MIC>1 mg/L时多数菌株出现Thr574-(Asn)、Ser575-Thr、Gln576-Gly(、Phe)577-(Tyr)4个连续残基的置换变异和Thr371-Ser的置换。PBP2B在所有MIC≤1 mg/L的PSSP中均未发生任何突变;而当MIC分别大于1 mg/L和2 mg/L时,均出现445Thr-Ala和Glu338-Gly。结论 PBP1A、PBP2B基因突变分别可导致其表达的PBP1A、PBP2B结构异常,与青霉素(包括其他β内酰胺类抗生素)亲和力下降,继而青霉素耐药。Objective To explore the relationship between minimal inhibitory concentrations（MIC） of penicillin against streptococcus pneumoniae（Sp） and mutation of penicillin-binding proteins（PBP）1A,2B and 2X. Methods Fifty-one Sp strains were tested for penicillin sensitivity by MIC method,and DNA was extracted from each Sp strain,and PBP of PBP1A and PBP2B were amplified by polymerase chain reaction（PCR） followed by DNA sequencing.Amino acid sequences of PBP1A and PBD2B in conserved motifs were deduced by Clustalx software program. Results In all MIC≤1 mg/L of Sp,PBP1A was not found any mutation;while in MIC1 mg/L,mutations appeared in most strains in several different sites,such as Thr574-（Asn）,Ser575-Thr,Gln576-Gly,and（Phe） 577-（Tyr） four consecutive residues,and the replacement of Thr371-Ser;any mutations of PBP2B were not found in PSSP when MIC≤1 mg/L;when MIC was greater than 1 mg/L and 2 mg/L,both 445Thr-Ala and Glu338-Gly appeared. Conclusion The mutation of PBP1A and PBP2B gene can lead to structural abnormalities of PBP1A-and-PBP2B-expressed PBP1A and PBP2B,decreasing the affinity with penicillin and other β-lactam antibiotics,and thus resistant to penicillin.

关 键 词：肺炎链球菌感染 青霉素结合蛋白类 青霉素类 微生物敏感性试验 

分 类 号：R446.5[医药卫生—诊断学]