三型分泌系统效应蛋白调控细胞凋亡和焦亡的研究进展
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摘要
病原菌感染对人类健康构成了严重的威胁,一类具有三型分泌系统(Type Ⅲ secretion system,T3SS)的致病菌,可以通过T3SS将效应蛋白"注射"到宿主细胞中,去干扰宿主细胞的多种信号转导通路,从而促进病原菌的增殖和传播。T3SS效应蛋白对宿主的影响被广泛研究,并且不同病原菌采取相似或不同的策略,同一种病原菌的效应蛋白又具有协同或拮抗的功能。综述了T3SS效应蛋白参与宿主细胞凋亡和焦亡信号通路过程中所发挥的功能及分子机制的最新研究进展,并进行了归纳分析,旨在为T3SS效应蛋白的深入研究提供参考和思路,从而进一步推进病原菌致病机制的研究,为防治病原菌提供理论基础。
Pathogenic bacterial infection causes a serious threat to human health. Pathogens that harbor a Type Ⅲ Secretion System(T3 SS)can inject effectors into host cells through T3SS and manipulate multiple signaling pathways,thereby facilitating the proliferation and dissemination of pathogens. T3SS effectors play important roles in the signaling pathways involved in apoptosis and pyroptosis of host cells. The effects of T3SS effectors on host have been widely investigated,the effectors of different pathogens exert similarly or differently functions,and the effectors of one species exhibit synergistic or antagonistic roles. Here,we reviewed the latest researches on the function and mechanism of T3SS effectors involved in cell apoptosis and pyroptosis,and made a summary and analysis. It aims to provide references and insight for intensively researching it,thus promoting research on the mechanism of pathogenic bacteria and providing theoretical basis of prevention and treatment of pathogens.
Pathogenic bacterial infection causes a serious threat to human health. Pathogens that harbor a Type Ⅲ Secretion System(T3 SS)can inject effectors into host cells through T3SS and manipulate multiple signaling pathways,thereby facilitating the proliferation and dissemination of pathogens. T3SS effectors play important roles in the signaling pathways involved in apoptosis and pyroptosis of host cells. The effects of T3SS effectors on host have been widely investigated,the effectors of different pathogens exert similarly or differently functions,and the effectors of one species exhibit synergistic or antagonistic roles. Here,we reviewed the latest researches on the function and mechanism of T3SS effectors involved in cell apoptosis and pyroptosis,and made a summary and analysis. It aims to provide references and insight for intensively researching it,thus promoting research on the mechanism of pathogenic bacteria and providing theoretical basis of prevention and treatment of pathogens.
引文
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[11]Berger CN,et al.EspZ of enteropathogenic and enterohemorrhagic Escherichia coli regulates type III secretionsystem protein translocation[J].MBio,2012,3(5),pii:e00317-e00312.
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[13]Shames SR,et al.The pathogenic E.coli type III effector EspZinteracts with host CD98 and facilitates host cell prosurvival signaling[J].Cell Microbiol,2010,12(9):1322-1339.
[14]Shames SR,Croxen MA,Deng W,et al.The type III systemsecreted effector EspZ localizes to host mitochondria and interacts with the translocase of inner mitochondrial membrane 17b[J].Infect Immun,2011,79(12):4784-4790.
[15]Roxas JL,et al.Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells[J].Am JPhysiol Gastrointest Liver Physiol,2014,307(3):G374-380.
[16]Bergounioux J,Elisee R,Prunier AL,et al.Calpain activation by the Shigella flexneri effector VirA regulates key steps in the formation and life of the bacterium’s epithelial niche[J].Cell Host Microbe,2012,11(3):240-252.
[17]Pendaries C,Tronchère H,Arbibe L,et al.PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection[J].EMBO J,2006,25(5):1024-1034.
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[19]Clark CS,Maurelli AT.Shigella flexneri inhibits staurosporineinduced apoptosis in epithelial cells[J].Infect Immun,2007,75(5):2531-2539.
[20]Mou X,et al.Synthetic bottom-up approach reveals the complex interplay of Shigella effectors in regulation of epithelial cell death[J].Proc Natl Acad Sci USA,2018,115(25):6452-6457.
[21]Knodler LA,Finlay BB,Steele-Mortimer O.The Salmonella effector protein SopB protects epithelial cells from apoptosis by sustained activation of Akt[J].J Biol Chem,2005,10:9058-9064.
[22]Jones RM,Wu H,et al.Salmonella AvrA coordinates suppression of host immune and apoptotic defenses via JNK pathway blockade[J].Cell Host Microbe,2008,3(4):233-244.
[23]Günster RA,Matthews SA,Holden DW,et al.SseK1 and SseK3type III secretion system effectors inhibit NF-κB signaling and necroptotic cell death in Salmonella-Infected Macrophages[J].Infect Immun.2017,85(3),pii:e00010-e00017.
[24]El Qaidi S,Chen K,Halim A,et al.NleB/SseK effectors from Citrobacter rodentium,Escherichia coli,and Salmonella enterica display distinct differences in host substrate specificity[J].JBiol Chem,2017,292(27):11423-11430.
[25]Esposito D,Günster RA,Martino L,et al.Structural basis for the glycosyltransferase activity of the Salmonella effector SseK3[J].J Biol Chem.2018,293(14):5064-5078.
[26]Park JB,Kim YH,Yoo Y,et al.Structural basis for arginine glycosylation of host substrates by bacterial effector proteins[J].Nat Commun,2018,9(1):4283.
[27]Nougayrède JP,Donnenberg MS.Enteropathogenic Escherichia coli EspF is targeted to mitochondria and is required to initiate the mitochondrial death pathway[J].Cell Microbiol,2004,6(11):1097-1111.
[28]Nougayrède JP,Foster GH,Donnenberg MS.Enteropathogenic Escherichia coli effector EspF interacts with host protein Abcf2[J].Cell Microbiol.2007,9(3):680-693.
[29]Samba-Louaka A,Nougayrède JP,Watrin C,et al.The enteropathogenic Escherichia coli effector Cif induces delayed apoptosis in epithelial cells[J].Infect Immun,2009,77(12):5471-5477.
[30]De Rycke J,Comtet E,Chalareng C,et al.Enteropathogenic Escherichia coli O103 from rabbit elicits actin stress fibers and focal adhesions in HeLa epithelial cells,cytopathic effects that are linked to an analog of the locus of enterocyte effacement[J].Infect Immun,1997,65(7):2555-2563.
[31]Morikawa H,et al.The bacterial effector Cif interferes with SCF ubiquitin ligase function by inhibiting deneddylationof Cullin1[J].Biochem Biophys Res Commun,2010,2:268-274.
[32]Nougayrède JP,et al.Type III secretion-dependent cell cycle block caused in HeLa cells by enteropathogenic Escherichia coli O103[J].Infect Immun,2001,11:6785-6795.
[33]Petroski MD,Deshaies RJ.Function and regulation of cullin-RINGubiquitin ligases[J].Nat Rev Mol Cell Biol,2005,6(1):9-20.
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