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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2022, Vol. 42 Issue (7): 69-78    DOI: 10.13523/j.cb.2202016
综述     
鼠伤寒沙门菌入侵宿主细胞机制研究进展*
闫春晓1,吴昊1,2,阮海华3,袁琳1,宋倩倩1,乔建军1,2,**()
1. 天津大学化工学院 系统生物工程教育部重点实验室 天津 300072
2. 天津大学浙江绍兴研究院 绍兴 312000
3. 天津市食品科学与生物技术重点实验室 天津 300134
Research Progress on the Salmonella typhimurium Invading Host Cells
Chun-xiao YAN1,Hao WU1,2,Hai-hua RUAN3,Lin YUAN1,Qian-qian SONG1,Jian-jun QIAO1,2,**()
1. Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering, Tianjin University, Tianjin 300072, China
2. Zhejiang Shaoxing Research Institute, Tianjin University, Shaoxing 312000, China
3. Tianjin Key Laboratory of Food Science and Biotechnology, Tianjin 300134, China
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摘要：

鼠伤寒沙门菌(Salmonella typhimurium)是一种人畜共患的肠道病原菌,可引起肠道炎症。该病原菌主要通过其致病岛(SPIs)编码的III型分泌系统(T3SS)分泌效应因子,包括促炎因子和抗炎因子。其在入侵肠上皮细胞时会释放促炎因子引发炎症反应,同时,为防止促炎因子过度破坏宿主细胞影响菌体的生存和繁殖,鼠伤寒沙门菌会产生一系列抗炎因子来调节细胞内信号通路,与宿主共同繁殖并最终全身扩散造成严重感染。旨在对鼠伤寒沙门菌利用T3SS效应因子入侵并调节宿主细胞信号通路机制进行概述。
关键词： 鼠伤寒沙门菌;  T3SS;  促炎因子;  抗炎因子    
Abstract:

Salmonella typhimurium is a zoonotic intestinal pathogen, which can cause intestinal inflammation. Effectors are mainly secreted through the type III secretion system(T3SS) encoded by its pathogenic islands (SPIs) to invade host cells and regulate cell signaling pathways, including pro-inflammatory effectors and anti-inflammatory factors. Pro-inflammatory effectors are released to cause inflammation when Salmonella typhimurium invades intestinal epithelial cells. In order to prevent excessive damage of host cells by pro-inflammatory effectors affecting the survival and reproduction of bacteria, Salmonella typhimurium can produce a series of anti-inflammatory factors to regulate intracellular signaling pathways, co-produce with the host and eventually spread throughout the body to cause severe infection. This paper provides an overview of the mechanism by which Salmonella typhimurium utilizes T3SS effectors to invade host cells and regulate cell signaling pathways.
Key words: Salmonella typhimurium    T3SS    Pro-inflammatory effector    Anti-inflammatory effector
收稿日期: 2022-02-15 出版日期: 2022-08-03
ZTFLH:  Q819  
基金资助: *国家重点研发计划(2019YFA0905600);国家自然科学基金创新研究群体(21621004)
通讯作者: 乔建军     E-mail: jianjunq@tju.edu.cn
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闫春晓
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乔建军

引用本文:

闫春晓,吴昊,阮海华,袁琳,宋倩倩,乔建军. 鼠伤寒沙门菌入侵宿主细胞机制研究进展*[J]. 中国生物工程杂志, 2022, 42(7): 69-78.

Chun-xiao YAN,Hao WU,Hai-hua RUAN,Lin YUAN,Qian-qian SONG,Jian-jun QIAO. Research Progress on the Salmonella typhimurium Invading Host Cells. China Biotechnology, 2022, 42(7): 69-78.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2202016    或    https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I7/69

图1  T3SS的针状复合体结构[21]
图2  T3SS分泌的促炎因子的作用机制
图3  T3SS分泌的抗炎因子的作用机制
效应因子类型 信号通路 效应因子 功能 参考文献
既是促炎因子
又是抗炎因子		 Rab8依赖的PI3K-Akt SopD 拮抗Rab8依赖的抗炎通路(GAP活性)
激活Rab8依赖的抗炎通路(Rab8的GDI解离因子)		 [27]
Rho家族GTPases
Rab8依赖的PI3K-Akt		 SopB 激活Rho家族GTPases SGEF(肌醇磷酯酶)
激活PI3K-Akt-YAP抗炎通路(肌醇磷酯酶)		 [29-30]
促炎因子 RIG-I和MDA5 SopA 激活RIG-I和MDA5(E3泛素连接酶) [45]
Rho家族GTPases SopE/SopE2 激活NF - κ B信号通路(Rho家族GTPases的GEFs) [51]
抗炎因子 Rho家族GTPases SptP 抑制REK和JNK激活(GAP活性) [56-58]
MAPK AvrA 抑制JNK激活(乙酰化Mkk4和Mkk7) [60]
SpvC 抑制ERK1, ERK2和p38激活(磷酸苏氨酸裂解酶) [63]
NF-κB PipA/GtgA/GogA 抑制NF-κB信号通路(RelA和RelB的蛋白酶) [66]
SseK1/SseK2/SseK3 抑制NF-κB信号通路(N-乙酰氨基葡糖转移酶) [69]
GopB 抑制NF-κB信号通路(抑制IκBα降解) [73]
SpvD 抑制NF-κB信号通路(抑制RelA) [78]
STAT3 SteE 激活STAT3依赖的抗炎信号通路 [80]
表1  鼠伤寒沙门菌III型分泌系统分泌的效应因子及功能
[1] Johnson R, Mylona E, Frankel G. Typhoidal Salmonella: distinctive virulence factors and pathogenesis. Cellular Microbiology, 2018, 20(9): e12939.
doi: 10.1111/cmi.12939
[2] Figueira R, Holden D W. Functions of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system effectors. Microbiology (Reading, England), 2012, 158(Pt 5): 1147-1161.
doi: 10.1099/mic.0.058115-0
[3] Ibarra J A, Steele-Mortimer O. Salmonella- the ultimate insider. Salmonella virulence factors that modulate intracellular survival. Cellular Microbiology, 2009, 11(11): 1579-1586.
doi: 10.1111/j.1462-5822.2009.01368.x
[4] Rogers A W L, Tsolis R M, Bäumler A J. Salmonella versus the microbiome. Microbiology and Molecular Biology Reviews: MMBR, 2020, 85(1): e00027-e00019.
[5] Winter S E, Thiennimitr P, Winter M G, et al. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature, 2010, 467(7314): 426-429.
doi: 10.1038/nature09415
[6] Zeng M Y, Inohara N, Nuñez G. Mechanisms of inflammation-driven bacterial dysbiosis in the gut. Mucosal Immunology, 2017, 10(1): 18-26.
doi: 10.1038/mi.2016.75 pmid: 27554295
[7] Stecher B, Robbiani R, Walker A W, et al. Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. PLoS Biology, 2007, 5(10): 2177-2189.
doi: 10.1371/journal.pbio.0050244 pmid: 17760501
[8] Galán J E. Salmonella typhimurium and inflammation: a pathogen-centric affair. Nature Reviews Microbiology, 2021, 19(11): 716-725.
doi: 10.1038/s41579-021-00561-4
[9] Worrall L J, Vuckovic M, Strynadka N C J. Crystal structure of the C-terminal domain of the Salmonella type III secretion system export apparatus protein InvA. Protein Science, 2010, 19(5): 1091-1096.
doi: 10.1002/pro.382 pmid: 20306492
[10] Miletic S, Fahrenkamp D, Goessweiner-Mohr N, et al. Substrate-engaged type III secretion system structures reveal gating mechanism for unfolded protein translocation. Nature Communications, 2021, 12: 1546.
doi: 10.1038/s41467-021-21143-1 pmid: 33750771
[11] Schraidt O, Lefebre M D, Brunner M J, et al. Topology and organization of the Salmonella typhimurium type III secretion needle complex components. PLoS Pathogens, 2010, 6(4): e1000824.
doi: 10.1371/journal.ppat.1000824
[12] Marlovits T C, Kubori T, Sukhan A, et al. Structural insights into the assembly of the type III secretion needle complex. Science, 2004, 306(5698): 1040-1042.
pmid: 15528446
[13] Rathinavelan T, Lara-Tejero M, Lefebre M, et al. NMR model of PrgI-SipD interaction and its implications in the needle-tip assembly of the Salmonella type III secretion system. Journal of Molecular Biology, 2014, 426(16): 2958-2969.
doi: 10.1016/j.jmb.2014.06.009
[14] Kaniga K, Tucker S, Trollinger D, et al. Homologs of the Shigella IpaB and IpaC invasins are required for Salmonella typhimurium entry into cultured epithelial cells. Journal of Bacteriology, 1995, 177(14): 3965-3971.
pmid: 7608068
[15] Myeni S K, Wang L, Zhou D G. SipB-SipC complex is essential for translocon formation. PLoS One, 2013, 8(3): e60499.
doi: 10.1371/journal.pone.0060499
[16] Lunelli M, Hurwitz R, Lambers J, et al. Crystal structure of PrgI-SipD: insight into a secretion competent state of the type three secretion system needle tip and its interaction with host ligands. PLoS Pathogens, 2011, 7(8): e1002163.
doi: 10.1371/journal.ppat.1002163
[17] Glasgow A A, Wong H T, Tullman-Ercek D. A secretion-amplification role for Salmonella enterica translocon protein SipD. ACS Synthetic Biology, 2017, 6(6): 1006-1015.
doi: 10.1021/acssynbio.6b00335 pmid: 28301138
[18] Wall D M, Nadeau W J, Pazos M A, et al. Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Cellular Microbiology, 2007, 9(9): 2299-2313.
doi: 10.1111/j.1462-5822.2007.00960.x
[19] Srikanth C V, Wall D M, Maldonado-Contreras A, et al. Salmonella pathogenesis and processing of secreted effectors by caspase-3. Science, 2010, 330(6002): 390-393.
doi: 10.1126/science.1194598 pmid: 20947770
[20] Keestra A M, Winter M G, Klein-Douwel D, et al. A Salmonella virulence factor activates the NOD1/NOD 2 signaling pathway. mBio, 2011, 2(6): e00266-e00211.
[21] Lou L X, Zhang P, Piao R L, et al. Salmonella pathogenicity island 1 (SPI-1) and its complex regulatory network. Frontiers in Cellular and Infection Microbiology, 2019, 9: 270.
doi: 10.3389/fcimb.2019.00270
[22] Friebel A, Ilchmann H, Aepfelbacher M, et al. SopE and SopE 2 from Salmonella typhimurium activate different sets of RhoGTPases of the host cell. Journal of Biological Chemistry, 2001, 276(36): 34035-34040.
doi: 10.1074/jbc.M100609200 pmid: 11440999
[23] Patel J C, Galán J E. Differential activation and function of Rho GTPases during Salmonella-host cell interactions. The Journal of Cell Biology, 2006, 175(3): 453-463.
doi: 10.1083/jcb.200605144
[24] Hardt W D, Chen L M, Schuebel K E, et al. S. typhimurium encodes an activator of rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell, 1998, 93(5): 815-826.
pmid: 9630225
[25] Hobbie S, Chen L M, Davis R J, et al. Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells. Journal of Immunology (Baltimore, Md: 1950), 1997, 159(11): 5550-5559.
[26] Sun H, Kamanova J, Lara-Tejero M, et al. A family of Salmonella type III secretion effector proteins selectively targets the NF-κB signaling pathway to preserve host homeostasis. PLoS Pathogens, 2016, 12(3): e1005484.
doi: 10.1371/journal.ppat.1005484
[27] Lian H, Jiang K, Tong M, et al. The Salmonella effector protein SopD targets Rab 8 to positively and negatively modulate the inflammatory response. Nature Microbiology, 2021, 6(5): 658-671.
doi: 10.1038/s41564-021-00866-3
[28] Panagi I, Jennings E, Zeng J K, et al. Salmonella effector SteE converts the mammalian serine/threonine kinase GSK 3 into a tyrosine kinase to direct macrophage polarization. Cell Host & Microbe, 2020, 27(1): 41-53.e6.
[29] Norris F A, Wilson M P, Wallis T S, et al. SopB, a protein required for virulence of Salmonella Dublin, is an inositol phosphate phosphatase. Proceedings of the National Academy of Sciences of the United States of America, 1998, 95(24): 14057-14059.
[30] Steele-Mortimer O, Knodler L A, Marcus S L, et al. Activation of Akt/protein kinase B in epithelial cells by the Salmonella typhimurium effector SigD. Journal of Biological Chemistry, 2000, 275(48): 37718-37724.
doi: 10.1074/jbc.M008187200 pmid: 10978351
[31] Bagci H, Sriskandarajah N, Robert A, et al. Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature Cell Biology, 2020, 22(1): 120-134.
doi: 10.1038/s41556-019-0438-7
[32] Rossman K L, Der C J, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nature Reviews Molecular Cell Biology, 2005, 6(2): 167-180.
pmid: 15688002
[33] Weston C R, Davis R J. The JNK signal transduction pathway. Current Opinion in Cell Biology, 2007, 19(2): 142-149.
doi: 10.1016/j.ceb.2007.02.001
[34] Oeckinghaus A, Ghosh S. The NF-κB family of transcription factors and its regulation. Cold Spring Harbor Perspectives in Biology, 2009, 1(4): a000034.
[35] Rahman M M, McFadden G. Modulation of NF-κB signalling by microbial pathogens. Nature Reviews Microbiology, 2011, 9(4): 291-306.
doi: 10.1038/nrmicro2539
[36] Tong S J, Wall A A, Hung Y, et al. Guanine nucleotide exchange factors activate Rab8a for Toll-like receptor signalling. Small GTPases, 2021, 12(1): 27-43.
doi: 10.1080/21541248.2019.1587278
[37] Hillmer E J, Zhang H Y, Li H S, et al. STAT 3 signaling in immunity. Cytokine & Growth Factor Reviews, 2016, 31: 1-15.
[38] Johnson D E, O’Keefe R A, Grandis J R. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nature Reviews Clinical Oncology, 2018, 15(4): 234-248.
doi: 10.1038/nrclinonc.2018.8 pmid: 29405201
[39] Lin T, Bost K L. STAT 3 activation in macrophages following infection with Salmonella. Biochemical and Biophysical Research Communications, 2004, 321(4): 828-834.
doi: 10.1016/j.bbrc.2004.07.039
[40] Karin M, Lawrence T, Nizet V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell, 2006, 124(4): 823-835.
doi: 10.1016/j.cell.2006.02.016
[41] Miao E A, Mao D P, Yudkovsky N, et al. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. PNAS, 2010, 107(7): 3076-3080.
[42] Bruno V M, Hannemann S, Lara-Tejero M, et al. Salmonella typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells. PLoS Pathogens, 2009, 5(8): e1000538.
doi: 10.1371/journal.ppat.1000538
[43] Marcus S L, Knodler L A, Finlay B B. Salmonella enterica serovar typhimurium effector SigD/SopB is membrane-associated and ubiquitinated inside host cells. Cellular Microbiology, 2002, 4(7): 435-446.
doi: 10.1046/j.1462-5822.2002.00202.x
[44] Zhang Y, Higashide W M, McCormick B A, et al. The inflammation-associated Salmonella SopA is a HECT-like E 3 ubiquitin ligase. Molecular Microbiology, 2006, 62(3): 786-793.
pmid: 17076670
[45] Versteeg G A, Rajsbaum R, Sánchez-Aparicio M T, et al. The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors. Immunity, 2013, 38(2): 384-398.
doi: 10.1016/j.immuni.2012.11.013 pmid: 23438823
[46] Wotzka S Y, Nguyen B D, Hardt W D. Salmonella typhimurium diarrhea reveals basic principles of enteropathogen infection and disease-promoted DNA exchange. Cell Host & Microbe, 2017, 21(4): 443-454.
[47] Zhou D, Chen L M, Hernandez L, et al. A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Molecular Microbiology, 2001, 39(2): 248-259.
pmid: 11136447
[48] Chen L M, Hobbie S, Galán J E. Requirement of CDC 42 for Salmonella-induced cytoskeletal and nuclear responses. Science, 1996, 274(5295): 2115-2118.
pmid: 8953049
[49] Misselwitz B, Dilling S, Vonaesch P, et al. RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42. Molecular Systems Biology, 2011, 7: 474.
doi: 10.1038/msb.2011.7 pmid: 21407211
[50] Mirold S, Ehrbar K, Weissmüller A, et al. Salmonella host cell invasion emerged by acquisition of a mosaic of separate genetic elements, including Salmonella pathogenicity island 1 (SPI1), SPI5, and sopE2. Journal of Bacteriology, 2001, 183(7): 2348-2358.
pmid: 11244077
[51] Sun H, Kamanova J, Lara-Tejero M, et al. Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors. Nature Microbiology, 2018, 3(10): 1122-1130.
doi: 10.1038/s41564-018-0246-z
[52] Savitskiy S, Itzen A. SopD from Salmonella specifically inactivates Rab8. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2021, 1869(8): 140661.
doi: 10.1016/j.bbapap.2021.140661
[53] Dixit E, Kagan J C. Intracellular pathogen detection by RIG-I-like receptors. Advances in Immunology, 2013, 117: 99-125.
[54] Tsuchida T, Zou J, Saitoh T, et al. The ubiquitin ligase TRIM 56 regulates innate immune responses to intracellular double-stranded DNA. Immunity, 2010, 33(5): 765-776.
doi: 10.1016/j.immuni.2010.10.013 pmid: 21074459
[55] Kamanova J, Sun H, Lara-Tejero M, et al. The Salmonella effector protein SopA modulates innate immune responses by targeting TRIM E 3 ligase family members. PLoS Pathogens, 2016, 12(4): e1005552.
doi: 10.1371/journal.ppat.1005552
[56] Johnson R, Byrne A, Berger C N, et al. The type III secretion system effector SptP of Salmonella enterica serovar typhi. Journal of Bacteriology, 2017, 199(4): e00647-e00616.
[57] Fu Y X, Galán J E. A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature, 1999, 401(6750): 293-297.
doi: 10.1038/45829
[58] Lin S L, Le T X, Cowen D S. SptP, a Salmonella typhimurium type III-secreted protein, inhibits the mitogen-activated protein kinase pathway by inhibiting Raf activation. Cellular Microbiology, 2003, 5(4): 267-275.
doi: 10.1046/j.1462-5822.2003.t01-1-00274.x
[59] Liu J, Lin A. Wiring the cell signaling circuitry by the NF-kappa B and JNK1 crosstalk and its applications in human diseases. Oncogene, 2007, 26(22): 3267-3278.
pmid: 17496921
[60] Jones R M, Wu H X, Wentworth C, et al. Salmonella AvrA coordinates suppression of host immune and apoptotic defenses via JNK pathway blockade. Cell Host & Microbe, 2008, 3(4): 233-244.
[61] Ye Z D, Petrof E O, Boone D, et al. Salmonella effector AvrA regulation of colonic epithelial cell inflammation by deubiquitination. The American Journal of Pathology, 2007, 171(3): 882-892.
doi: 10.2353/ajpath.2007.070220
[62] Newton I L G, Woyke T, Auchtung T A, et al. The Calyptogena magnifica chemoautotrophic symbiont genome. Science, 2007, 315(5814): 998-1000.
pmid: 17303757
[63] Haneda T, Ishii Y, Shimizu H, et al. Salmonella type III effector SpvC, a phosphothreonine lyase, contributes to reduction in inflammatory response during intestinal phase of infection. Cellular Microbiology, 2012, 14(4): 485-499.
doi: 10.1111/j.1462-5822.2011.01733.x
[64] Mazurkiewicz P, Thomas J, Thompson J A, et al. SpvC is a Salmonella effector with phosphothreonine lyase activity on host mitogen-activated protein kinases. Molecular Microbiology, 2008, 67(6): 1371-1383.
doi: 10.1111/j.1365-2958.2008.06134.x pmid: 18284579
[65] Zuo L L, Zhou L T, Wu C Y, et al. Salmonella spvC gene inhibits pyroptosis and intestinal inflammation to aggravate systemic infection in mice. Frontiers in Microbiology, 2020, 11: 562491.
doi: 10.3389/fmicb.2020.562491
[66] Takemura M, Haneda T, Idei H, et al. A Salmonella type III effector, PipA, works in a different manner than the PipA family effectors GogA and GtgA. PLoS One, 2021, 16(3): e0248975.
doi: 10.1371/journal.pone.0248975
[67] Kujat Choy S L, Boyle E C, Gal-Mor O, et al. SseK1 and SseK 2 are novel translocated proteins of Salmonella enterica serovar typhimurium. Infection and Immunity, 2004, 72(9): 5115-5125.
doi: 10.1128/IAI.72.9.5115-5125.2004
[68] Newton H J, Pearson J S, Badea L, et al. The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLoS Pathogens, 2010, 6(5): e1000898.
doi: 10.1371/journal.ppat.1000898
[69] Li S, Zhang L, Yao Q, et al. Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains. Nature, 2013, 501(7466): 242-246.
[70] Pobezinskaya Y L, Kim Y S, Choksi S, et al. The function of TRADD in signaling through tumor necrosis factor receptor 1 and TRIF-dependent Toll-like receptors. Nature Immunology, 2008, 9(9): 1047-1054.
doi: 10.1038/ni.1639 pmid: 18641653
[71] Coombes B K, Wickham M E, Brown N F, et al. Genetic and molecular analysis of GogB, a phage-encoded type III-secreted substrate in Salmonella enterica serovar typhimurium with autonomous expression from its associated phage. Journal of Molecular Biology, 2005, 348(4): 817-830.
pmid: 15843015
[72] Quezada C M, Hicks S W, Galán J E, et al. A family of Salmonella virulence factors functions as a distinct class of autoregulated E 3 ubiquitin ligases. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(12): 4864-4869.
[73] Zheng N, Schulman B A, Song L Z, et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp 2 SCF ubiquitin ligase complex. Nature, 2002, 416(6882): 703-709.
doi: 10.1038/416703a
[74] Pilar A V C, Reid-Yu S A, Cooper C A, et al. GogB is an anti-inflammatory effector that limits tissue damage during Salmonella infection through interaction with human FBXO22 and Skp1. PLoS Pathogens, 2012, 8(6): e1002773.
doi: 10.1371/journal.ppat.1002773
[75] Kutay U, Bischoff F R, Kostka S, et al. Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. Cell, 1997, 90(6): 1061-1071.
pmid: 9323134
[76] Liang P Z, Zhang H Y, Wang G X, et al. KPNB1, XPO7 and IPO 8 mediate the translocation of NF-κB/p65 into the nucleus. Traffic, 2013, 14(11): 1132-1143.
[77] Cunningham M D, Cleaveland J, Nadler S G. An intracellular targeted NLS peptide inhibitor of karyopherin alpha: NF-kappa B interactions. Biochemical and Biophysical Research Communications, 2003, 300(2): 403-407.
pmid: 12504098
[78] Rolhion N, Furniss R C D, Grabe G, et al. Inhibition of nuclear transport of NF-κB p 65 by the Salmonella type III secretion system effector SpvD. PLoS Pathogens, 2016, 12(5): e1005653.
doi: 10.1371/journal.ppat.1005653
[79] García-Gil A, Galán-Enríquez C S, Pérez-López A, et al. SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells. Virulence, 2018, 9(1): 1390-1402.
doi: 10.1080/21505594.2018.1509664 pmid: 30103648
[80] Jaslow S L, Gibbs K D, Fricke W F, et al. Salmonella activation of STAT3 signaling by SarA effector promotes intracellular replication and production of IL-10. Cell Reports, 2018, 23(12): 3525-3536.
doi: S2211-1247(18)30836-2 pmid: 29924996
[81] Stapels D A C, Hill P W S, Westermann A J, et al. Salmonella persisters undermine host immune defenses during antibiotic treatment. Science, 2018, 362(6419): 1156-1160.
doi: 10.1126/science.aat7148 pmid: 30523110
[82] Gibbs K D, Washington E J, Jaslow S L, et al. The Salmonella secreted effector SarA/SteE mimics cytokine receptor signaling to activate STAT3. Cell Host & Microbe, 2020, 27(1): 129-139.e4.
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