Service of Microbiology, University Hospital Marqués de Valdecilla—IFIMAV, and Department of Molecular Biology, School of Medicine, University of Cantabria, Barcelona, Barcelona, Spain.
Antimicrob Agents Chemother. 2011 Dec;55(12):5907-13. doi: 10.1128/AAC.00459-11. Epub 2011 Sep 26.
There is limited information on the role of penicillin-binding proteins (PBPs) in the resistance of Acinetobacter baumannii to β-lactams. This study presents an analysis of the allelic variations of PBP genes in A. baumannii isolates. Twenty-six A. baumannii clinical isolates (susceptible or resistant to carbapenems) from three teaching hospitals in Spain were included. The antimicrobial susceptibility profile, clonal pattern, and genomic species identification were also evaluated. Based on the six complete genomes of A. baumannii, the PBP genes were identified, and primers were designed for each gene. The nucleotide sequences of the genes identified that encode PBPs and the corresponding amino acid sequences were compared with those of ATCC 17978. Seven PBP genes and one monofunctional transglycosylase (MGT) gene were identified in the six genomes, encoding (i) four high-molecular-mass proteins (two of class A, PBP1a [ponA] and PBP1b [mrcB], and two of class B, PBP2 [pbpA or mrdA] and PBP3 [ftsI]), (ii) three low-molecular-mass proteins (two of type 5, PBP5/6 [dacC] and PBP6b [dacD], and one of type 7 (PBP7/8 [pbpG]), and (iii) a monofunctional enzyme (MtgA [mtgA]). Hot spot mutation regions were observed, although most of the allelic changes found translated into silent mutations. The amino acid consensus sequences corresponding to the PBP genes in the genomes and the clinical isolates were highly conserved. The changes found in amino acid sequences were associated with concrete clonal patterns but were not directly related to susceptibility or resistance to β-lactams. An insertion sequence disrupting the gene encoding PBP6b was identified in an endemic carbapenem-resistant clone in one of the participant hospitals.
青霉素结合蛋白（PBPs）在鲍曼不动杆菌对β-内酰胺类抗生素耐药性中的作用信息有限。本研究分析了鲍曼不动杆菌分离株中 PBP 基因的等位基因变异。纳入了西班牙三家教学医院的 26 株鲍曼不动杆菌临床分离株（对碳青霉烯类敏感或耐药）。还评估了抗菌药物敏感性谱、克隆模式和基因组种属鉴定。基于 6 株完整的鲍曼不动杆菌基因组，鉴定了 PBP 基因，并为每个基因设计了引物。鉴定出的编码 PBPs 的基因的核苷酸序列及其相应的氨基酸序列与 ATCC 17978 进行了比较。在这 6 个基因组中鉴定出 7 个 PBP 基因和 1 个单功能转糖基酶（MGT）基因，编码（i）4 种高分子量蛋白（2 种 A 类，PBP1a[ponA]和 PBP1b[mrcB]，2 种 B 类，PBP2[pbpA 或 mrdA]和 PBP3[ftsI]），（ii）3 种低分子量蛋白（2 种 5 型，PBP5/6[dacC]和 PBP6b[dacD]，1 种 7 型（PBP7/8[pbpG]）和（iii）1 种单功能酶（MtgA[mtgA]）。虽然发现的大多数等位基因变化导致沉默突变，但仍观察到热点突变区域。基因组和临床分离株中 PBP 基因的氨基酸共有序列高度保守。发现的氨基酸序列变化与具体的克隆模式相关，但与β-内酰胺类药物的敏感性或耐药性无关。在一家参与医院的地方性耐碳青霉烯类克隆中，发现了一个插入序列破坏了 PBP6b 基因的编码。
