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.
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。
相似文献
1
Detailed mutational analysis of Vga(A) interdomain linker: implication for antibiotic resistance specificity and mechanism.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
Antimicrob Agents Chemother. 2015 Feb;59(2):1360-4. doi: 10.1128/AAC.04468-14. Epub 2014 Dec 15.
2
Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and Mechanisms of Resistance.林可酰胺类、链阳菌素类、氯霉素类和截短侧耳素类：作用方式及耐药机制
Cold Spring Harb Perspect Med. 2016 Nov 1;6(11):a027037. doi: 10.1101/cshperspect.a027037.
3
Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens.ABC 转运蛋白介导的革兰阳性病原体对截短侧耳素、林可酰胺和链阳性菌素 A 抗生素耐药的结构基础。
Nat Commun. 2021 Jun 11;12(1):3577. doi: 10.1038/s41467-021-23753-1.
4
Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) gene in Streptococcus agalactiae UCN70.无乳链球菌 UCN70 中 lsa(C) 基因导致林可酰胺类、链阳性菌素 A 和截短侧耳素类交叉耐药。
Antimicrob Agents Chemother. 2011 Apr;55(4):1470-4. doi: 10.1128/AAC.01068-10. Epub 2011 Jan 18.
5
Identification of a novel vga(E) gene variant that confers resistance to pleuromutilins, lincosamides and streptogramin A antibiotics in staphylococci of porcine origin.鉴定一种新型 vga(E) 基因变异体，该变异体赋予猪源葡萄球菌对截短侧耳素类、林可酰胺类和链阳性菌素 A 类抗生素的耐药性。
J Antimicrob Chemother. 2014 Apr;69(4):919-23. doi: 10.1093/jac/dkt482. Epub 2013 Dec 8.
6
Small plasmids carrying vga(A) or vga(C) genes mediate resistance to lincosamides, pleuromutilins and streptogramin A antibiotics in methicillin-resistant Staphylococcus aureus ST398 from swine.携带vga(A)或vga(C)基因的小质粒介导来自猪的耐甲氧西林金黄色葡萄球菌ST398对林可酰胺类、截短侧耳素类和链阳菌素A类抗生素产生抗性。
J Antimicrob Chemother. 2010 Dec;65(12):2692-3. doi: 10.1093/jac/dkq365. Epub 2010 Sep 28.
7
Ribosome-Mediated Attenuation of (A) Expression Is Shaped by the Antibiotic Resistance Specificity of Vga(A) Protein Variants.核糖体介导的(A)表达衰减受 Vga(A)蛋白变体对抗生素耐药性特异性的影响。
Antimicrob Agents Chemother. 2020 Oct 20;64(11). doi: 10.1128/AAC.00666-20.
8
Characterization of (D), a Novel Gene Responsible for Resistance to Lincosamides, Streptogramins A, and Pleuromutilins in Fish Pathogenic Serotype II.（D）基因的特性研究，该基因为鱼类病原菌 II 型耐林可酰胺类、链阳性菌素 A 和截短侧耳素类药物的新型致因。
Microb Drug Resist. 2021 Mar;27(3):301-310. doi: 10.1089/mdr.2020.0218. Epub 2020 Jul 20.
9
A new evolutionary variant of the streptogramin A resistance protein, Vga(A)LC, from Staphylococcus haemolyticus with shifted substrate specificity towards lincosamides.一种来自溶血葡萄球菌的链阳菌素A抗性蛋白Vga(A)LC的新进化变体，其对林可酰胺类药物的底物特异性发生了改变。
Antimicrob Agents Chemother. 2006 Dec;50(12):4070-6. doi: 10.1128/AAC.00799-06. Epub 2006 Oct 2.
10
Genetic basis for in vitro and in vivo resistance to lincosamides, streptogramins A, and pleuromutilins (LSAP phenotype) in Enterococcus faecium.肠球菌对林可酰胺类、链阳性菌素 A 和截短侧耳素（LSAP 表型）的体外和体内耐药的遗传基础。
Antimicrob Agents Chemother. 2013 Sep;57(9):4463-9. doi: 10.1128/AAC.01030-13. Epub 2013 Jul 8.
引用本文的文献
1
ABCF protein-mediated resistance shapes bacterial responses to antibiotics based on their type and concentration.ABCF蛋白介导的耐药性根据抗生素的类型和浓度塑造细菌对抗生素的反应。
mBio. 2025 Sep 10;16(9):e0156825. doi: 10.1128/mbio.01568-25. Epub 2025 Aug 12.
2
Global regulation via modulation of ribosome pausing by the ABC-F protein EttA.通过 ABC-F 蛋白 EttA 调节核糖体暂停实现全球调控。
Nat Commun. 2024 Jul 26;15(1):6314. doi: 10.1038/s41467-024-50627-z.
3
Regulation of the macrolide resistance ABC-F translation factor MsrD.大环内酯类耐药 ABC-F 转运蛋白 MsrD 的调控。
Nat Commun. 2023 Jul 1;14(1):3891. doi: 10.1038/s41467-023-39553-8.
4
Functional characterization of the ABC transporters and transposable elements of an uncultured Paracoccus sp. recovered from a hydrocarbon-polluted soil metagenome.从烃污染土壤宏基因组中回收的未培养 Paracoccus sp. 的 ABC 转运蛋白和转座元件的功能特征。
Folia Microbiol (Praha). 2023 Apr;68(2):299-314. doi: 10.1007/s12223-022-01012-0. Epub 2022 Nov 3.
5
Gene rppA co-regulated by LRR, SigA, and CcpA mediates antibiotic resistance in Bacillus thuringiensis.LRR、SigA 和 CcpA 共同调控的 rppA 基因介导苏云金芽孢杆菌的抗生素抗性。
Appl Microbiol Biotechnol. 2022 Sep;106(17):5687-5699. doi: 10.1007/s00253-022-12090-y. Epub 2022 Jul 30.
6
Beyond Self-Resistance: ABCF ATPase LmrC Is a Signal-Transducing Component of an Antibiotic-Driven Signaling Cascade Accelerating the Onset of Lincomycin Biosynthesis.超越自我抵抗：ABCF ATP 酶 LmrC 是抗生素驱动信号级联的信号转导组件，可加速林可霉素生物合成的起始。
mBio. 2021 Oct 26;12(5):e0173121. doi: 10.1128/mBio.01731-21. Epub 2021 Sep 7.
7
Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens.ABC 转运蛋白介导的革兰阳性病原体对截短侧耳素、林可酰胺和链阳性菌素 A 抗生素耐药的结构基础。
Nat Commun. 2021 Jun 11;12(1):3577. doi: 10.1038/s41467-021-23753-1.
8
Ribosome Protection Proteins-"New" Players in the Global Arms Race with Antibiotic-Resistant Pathogens.核糖体保护蛋白——与抗生素耐药病原体全球军备竞赛中的“新”角色。
Int J Mol Sci. 2021 May 19;22(10):5356. doi: 10.3390/ijms22105356.
9
ABC-F translation factors: from antibiotic resistance to immune response.ABC-F 转运因子：从抗生素耐药到免疫反应
FEBS Lett. 2021 Mar;595(6):675-706. doi: 10.1002/1873-3468.13984. Epub 2020 Dec 4.
10
Ribosome-Mediated Attenuation of (A) Expression Is Shaped by the Antibiotic Resistance Specificity of Vga(A) Protein Variants.核糖体介导的(A)表达衰减受 Vga(A)蛋白变体对抗生素耐药性特异性的影响。
Antimicrob Agents Chemother. 2020 Oct 20;64(11). doi: 10.1128/AAC.00666-20.
本文引用的文献
1
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.
2
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。
Nat Struct Mol Biol. 2014 Feb;21(2):152-9. doi: 10.1038/nsmb.2741. Epub 2014 Jan 5.
3
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
Antimicrob Agents Chemother. 2013 Sep;57(9):4543-4546. doi: 10.1128/AAC.00259-13. Epub 2013 Jun 24.
4
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。
Res Microbiol. 2013 Apr;164(3):226-35. doi: 10.1016/j.resmic.2012.12.003. Epub 2012 Dec 20.
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.
6
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。
Diagn Microbiol Infect Dis. 2011 Oct;71(2):177-80. doi: 10.1016/j.diagmicrobio.2011.06.009.
7
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.
8
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。
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17152-7. doi: 10.1073/pnas.1007988107. Epub 2010 Sep 27.
9
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。
Nat Struct Mol Biol. 2010 May;17(5):555-60. doi: 10.1038/nsmb.1790. Epub 2010 Apr 18.
10
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.
Zotero 插件