The Carbapenemase BKC-1 from Klebsiella pneumoniae Is Adapted for Translocation by Both the Tat and Sec Translocons.
The Carbapenemase BKC-1 from Klebsiella pneumoniae Is Adapted for Translocation by Both the Tat and Sec Translocons.
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DOI：
10.1128/mbio.01302-21
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发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Lithgow T
中科院分区：
文献类型：
--
作者：
Bharathwaj M;Webb CT;Vadlamani G;Stubenrauch CJ;Palmer T;Lithgow T
革兰氏阴性菌的细胞被膜由包围周质和肽聚糖层的两层膜组成。β-内酰胺抗生素靶向合成肽聚糖的周质青霉素结合蛋白，导致细胞死亡。细菌抵抗β-内酰胺药物作用的主要手段是在周质间隙填充β-内酰胺酶。对β-内酰胺类药物的耐药性通过编码β-内酰胺酶的基因从一种细菌侧向转移到另一种细菌而传播。然而，抗性表型又取决于这些“外来”蛋白序列被新细菌宿主的Sec或达特蛋白易位机制识别并跨细胞质膜输出。在这里，我们检查BKC-1，一种来自未知细菌来源的碳青霉烯酶，已在肺炎克雷伯菌的单一临床分离株中鉴定。BKC-1定位于周质，在K.肺炎和大肠杆菌。序列分析表明，存在一个不寻常的信号肽与双精氨酸基序和重复的疏水区。生物化学分析表明，该信号肽指导BKC-1通过Sec和达特转座子进行易位。这是少数几个描述的周质蛋白，在同一个生物体中的两个输出途径的功能易位，我们认为它代表了一个β-内酰胺酶适应新宿主的功能进化的快照。
The cell envelope of Gram-negative bacteria consists of two membranes surrounding the periplasm and peptidoglycan layer. β-Lactam antibiotics target the periplasmic penicillin-binding proteins that synthesize peptidoglycan, resulting in cell death. The primary means by which bacterial species resist the effects of β-lactam drugs is to populate the periplasmic space with β-lactamases. Resistance to β-lactam drugs is spread by lateral transfer of genes encoding β-lactamases from one species of bacteria to another. However, the resistance phenotype depends in turn on these “alien” protein sequences being recognized and exported across the cytoplasmic membrane by either the Sec or Tat protein translocation machinery of the new bacterial host. Here, we examine BKC-1, a carbapenemase from an unknown bacterial source that has been identified in a single clinical isolate of Klebsiella pneumoniae. BKC-1 was shown to be located in the periplasm, and functional in both K. pneumoniae and Escherichia coli. Sequence analysis revealed the presence of an unusual signal peptide with a twin arginine motif and a duplicated hydrophobic region. Biochemical assays showed this signal peptide directs BKC-1 for translocation by both Sec and Tat translocons. This is one of the few descriptions of a periplasmic protein that is functionally translocated by both export pathways in the same organism, and we suggest it represents a snapshot of evolution for a β-lactamase adapting to functionality in a new host.
从paramemohizobium dedestii a-3-e（t）的新型A类A级Carbapenemase Pad的表征，这是一种对β-内酰胺抗生素高度抗性的菌株。
影响因子：
4.6
作者：
Lv R;Guo J;Yan Y;Chen R;Xiao L;Wang M;Fang N;Fang C;Cui Y;Yang R;Song Y
通讯作者：
Song Y