Sequence heterogeneity of the PenA carbapenemase in clinical isolates of Burkholderia multivorans.
Sequence heterogeneity of the PenA carbapenemase in clinical isolates of Burkholderia multivorans.
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DOI：
10.1016/j.diagmicrobio.2018.06.005
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发表时间：
2018-11
影响因子：
2.9
通讯作者：
Papp-Wallace KM
中科院分区：
文献类型：
--
作者：
Becka SA;Zeiser ET;Marshall SH;Gatta JA;Nguyen K;Singh I;Greco C;Sutton GG;Fouts DE;LiPuma JJ;Papp-Wallace KM
多重耐药革兰氏阴性病原体是一个重大的健康威胁。伯克氏菌属革兰氏阴性菌包括具有广泛生物学功能的革兰氏阴性菌的复杂子集，包括人类、动物和植物病原体。治疗伯克霍尔德氏菌属引起的感染。由于它们对多种抗生素的固有抗性，在伯克霍尔德菌属中表达的主要β-内酰胺类耐药决定簇。是佩纳家族的A类β-内酰胺酶。在这项研究中，在从囊性纤维化个体中分离的48种不同的多食伯克霍尔德菌菌株中的佩纳（37种新变体）中发现了显著的氨基酸序列异质性。系统发育分析将37个变异体根据其一级氨基酸序列分为5类。氨基酸取代存在于整个β-内酰胺酶中，并且不聚集于蛋白质的特定区域。佩纳变异体具有5至17个单个氨基酸变化。N189 S和S286 I置换是最普遍的，并且在所有变体中发现。由于佩纳中的序列异质性，选择佩纳中的高度保守肽（18个氨基酸）作为多克隆抗体生产的抗原，以测量B的48个临床分离株中佩纳的表达。多食动物。使用免疫印迹方法表征抗PenA肽抗体，暴露了该抗体的几个独特特征（即，检测到<500 pg的纯化佩纳，所有37种佩纳变体在B中。多噬菌体和洋葱伯克霍尔德菌复合体内来自其他物种的Pen样β-内酰胺酶）。在佩纳中发现的显著序列异质性可能是由于选择压力（例如，暴露于抗微生物治疗）。这些变化的贡献值得进一步研究。
Multidrug-resistant gram-negative pathogens are a significant health threat. Burkholderia spp. encompass a complex subset of gram-negative bacteria with a wide range of biological functions that include human, animal, and plant pathogens. The treatment of infections caused by Burkholderia spp. is problematic due to their inherent resistance to multiple antibiotics. The major β-lactam resistance determinant expressed in Burkholderia spp. is a class A β-lactamase of the PenA family. In this study, significant amino acid sequence heterogeneity was discovered in PenA (37 novel variants) within a panel of 48 different strains of Burkholderia multivorans isolated from individuals with cystic fibrosis. Phylogenetic analysis distributed the 37 variants into 5 groups based on their primary amino acid sequences. Amino acid substitutions were present throughout the entire β-lactamase and did not congregate to specific regions of the protein. The PenA variants possessed 5 to 17 single amino acid changes. The N189S and S286I substitutions were most prevalent and found in all variants. Due to the sequence heterogeneity in PenA, a highly conserved peptide (18 amino acids) within PenA was chosen as the antigen for polyclonal antibody production in order to measure expression of PenA within the 48 clinical isolates of B. multivorans. Characterization of the anti-PenA peptide antibody, using immunoblotting approaches, exposed several unique features of this antibody (i.e., detected <500 pg of purified PenA, all 37 PenA variants in B. multivorans, and Pen-like β-lactamases from other species within the Burkholderia cepacia complex). The significant sequence heterogeneity found in PenA may have occurred due to selective pressure (e.g., exposure to antimicrobial therapy) within the host. The contribution of these changes warrants further investigation.
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DOI：
10.1099/ijsem.0.002202
发表时间：
2017-10-01
影响因子：
2.8
作者：
Dobritsa, Anatoly P.;Linardopoulou, Elena V.;Samadpour, Mansour
通讯作者：
Samadpour, Mansour
影响因子：
4.9
作者：
Frase, Hilary;Toth, Marta;Vakulenko, Sergei B.
通讯作者：
Vakulenko, Sergei B.
影响因子：
4.9
作者：
PRINCE, A;WOOD, MS;CHIN, NX
通讯作者：
CHIN, NX
影响因子：
8.4
作者：
Deris, Zakuan Zainy;Van Rostenberghe, Hans;Ravichandran, Manicham
通讯作者：
Ravichandran, Manicham
影响因子：
3.6
作者：
Chiappini, Elena;Taccetti, Giovanni;de Martino, Maurizio
通讯作者：
de Martino, Maurizio