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Vga(A) 结构域间连接子的详细突变分析:对抗生素抗性特异性和机制的启示

Detailed mutational analysis of Vga(A) interdomain linker: implication for antibiotic resistance specificity and mechanism.

作者信息

Lenart Jakub, Vimberg Vladimir, Vesela Ludmila, Janata Jiri, Balikova Novotna Gabriela

机构信息

Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.

Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

出版信息

Antimicrob Agents Chemother. 2015 Feb;59(2):1360-4. doi: 10.1128/AAC.04468-14. Epub 2014 Dec 15.

DOI:10.1128/AAC.04468-14
PMID:25512423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4335903/
Abstract

Detailed mutational analysis examines the roles of individual residues of the Vga(A) linker in determining the antibiotic resistance phenotype. It defines a narrowed region of residues 212 to 220 whose composition determines the resistance specificity to lincosamides, pleuromutilins, and/or streptogramins A. From the analogy with the recently described function of the homologous ABC-F protein EttA as a translational factor, we infer that the Vga(A) linker interacts with the ribosome and directly or indirectly affects the binding of the respective antibiotic.

摘要

详细的突变分析研究了Vga(A)连接子中各个残基在决定抗生素抗性表型中的作用。它确定了一个残基范围缩小至212到220的区域,该区域的组成决定了对林可酰胺类、截短侧耳素类和/或链阳菌素A的抗性特异性。从与最近描述的同源ABC-F蛋白EttA作为翻译因子的功能类比中,我们推断Vga(A)连接子与核糖体相互作用,并直接或间接影响相应抗生素的结合。

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本文引用的文献

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The ABC-F protein EttA gates ribosome entry into the translation elongation cycle.ABC-F 蛋白 EttA 使核糖体进入翻译延伸循环。
Nat Struct Mol Biol. 2014 Feb;21(2):143-51. doi: 10.1038/nsmb.2740. Epub 2014 Jan 5.
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EttA regulates translation by binding the ribosomal E site and restricting ribosome-tRNA dynamics.EttA 通过结合核糖体 E 位点并限制核糖体-tRNA 动力学来调节翻译。
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Resistance Genes Underlying the LS Phenotype of Staphylococcal Isolates from France.法国葡萄球菌分离株LS表型的抗性基因
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Functional interplay between the ATP binding cassette Msr(D) protein and the membrane facilitator superfamily Mef(E) transporter for macrolide resistance in Escherichia coli.ATP 结合盒蛋白 Msr(D) 与膜促进因子超级家族 Mef(E) 转运蛋白在大肠杆菌中对大环内酯类抗生素耐药性的功能相互作用。
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5
Identification of novel vga(A)-carrying plasmids and a Tn5406-like transposon in meticillin-resistant Staphylococcus aureus and Staphylococcus epidermidis of human and animal origin.鉴定耐甲氧西林金黄色葡萄球菌和表皮葡萄球菌中人源和动物源携带 vga(A) 的新型质粒和 Tn5406 样转座子。
Int J Antimicrob Agents. 2012 Oct;40(4):306-12. doi: 10.1016/j.ijantimicag.2012.06.009. Epub 2012 Aug 14.
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Plasmid-borne vga(A)-encoding gene in methicillin-resistant Staphylococcus aureus ST398 recovered from swine and a swine farmer in the United States.从美国猪和一名养猪户中分离到的耐甲氧西林金黄色葡萄球菌 ST398 携带 vga(A) 编码基因的质粒。
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Two paediatric cases of skin and soft-tissue infections due to clindamycin-resistant Staphylococcus aureus carrying a plasmid-encoded vga(A) allelic variant for a putative efflux pump.两例儿童皮肤软组织感染由携带编码推测外排泵 vga(A) 等位变体的质粒的克林霉素耐药金黄色葡萄球菌引起。
Int J Antimicrob Agents. 2011 Jul;38(1):81-3. doi: 10.1016/j.ijantimicag.2011.03.007. Epub 2011 May 5.
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Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action.结合在肽基转移酶中心附近的抗生素的大肠杆菌核糖体结构解释了药物作用的光谱。
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Structural aspects of messenger RNA reading frame maintenance by the ribosome.核糖体维持信使 RNA 读码框的结构方面。
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Erythromycin resistance by L4/L22 mutations and resistance masking by drug efflux pump deficiency.由L4/L22突变导致的红霉素耐药性以及药物外排泵缺陷导致的耐药性掩盖。
EMBO J. 2009 Mar 18;28(6):736-44. doi: 10.1038/emboj.2009.17. Epub 2009 Feb 5.