布鲁氏菌毒力因子与胞内存活机制研究进展

doi:10.11843/j.issn.0366-6964.2025.04.010

摘要/Abstract

摘要：

布鲁氏菌病是一种重要的呈世界性流行的人兽共患病，给畜牧业造成巨大经济损失的同时，还严重威胁人类健康与公共卫生安全。布鲁氏菌可应用多种策略逃逸免疫系统，不仅可抵抗吞噬细胞的杀菌作用，还可使宿主细胞形成有利于自身存活的微环境，最终发展为慢性感染，这些策略给防控布鲁氏菌病带来了不小的挑战，作为进一步理解并防控布鲁氏菌病的前提，布鲁氏菌的毒力过程、胞内存活、免疫逃逸等一直是人们关注的重点，因此，本文从布鲁氏菌主要毒力因子、胞内存活和免疫逃避机制等方面，阐述其毒力因子及胞内存活机制研究进展，以期通过阐释布鲁氏菌致病机制为将来研发新型安全、高效的防控产品提供参考。

关键词: 布鲁氏菌, 毒力因子, 胞内存活, 致病机制

Abstract:

Brucellosis is an important zoonotic disease that is prevalent worldwide, while causing numerous economic losses to animal husbandry, it also poses a serious threat to human health and public health security. Brucella can use various strategies for immune system evasion, not only resisting the bactericidal effect of phagocytic cells, but also creating a favorable microenvironment in host cells for its survival, ultimately leading to persistent chronic infection. These characteristics pose significant challenges to the prevention and control of brucellosis. As a prerequisite for further understanding and preventing brucellosis, the virulence process, intracellular survival, and immune evasion of Brucella have always been the focus of attention. So, this work reviewed the Brucella pathogenesis research progress from perspectives of virulence factors, intracellular survival, and immune evasion mechanism, providing reference for future development of novel safe, efficient prevention and control products by elucidating Brucella pathogenesis.

Key words: Brucella, virulence factor, intracellular survival, pathogenesis

中图分类号:

R378.5

尤留超, 尹号, 陶政宇, 黄蓉, 付磊, 储岳峰. 布鲁氏菌毒力因子与胞内存活机制研究进展[J]. 畜牧兽医学报, 2025, 56(4): 1575-1593.

YOU Liuchao, YIN Hao, TAO Zhengyu, HUANG Rong, FU Lei, CHU Yuefeng. Research Progress in the Virulence Factors and Intracellular Survival Mechanism of Brucella[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(4): 1575-1593.

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参考文献 177

1	KHOSHNOODS,PAKZADR,KOUPAEIM,et al.Prevalence, diagnosis, and manifestations of brucellosis: A systematic review and meta-analysis[J].Front Vet Sci,2022,9,976215. doi: 10.3389/fvets.2022.976215
2	HULLN C,SCHUMAKERB A.Comparisons of brucellosis between human and veterinary medicine[J].Infect Ecol Epidemiol,2018,8(1):1500846.
3	ATLURIV L,XAVIERM N,de JONGM F,et al.Interactions of the human pathogenicbrucella species with their hosts[J].Ann Rev Microbiol,2011,65(1):523-541. doi: 10.1146/annurev-micro-090110-102905
4	YANGJ,WANGY,HOUY,et al.Evasion of host defense by Brucella[J].Cell Insight,2024,3(1):100143. doi: 10.1016/j.cellin.2023.100143
5	HEIDARYM,DASHTBINS,GHANAVATIR,et al.Evaluation of brucellosis vaccines: A comprehensive review[J].Front Vet Sci,2022,9,925773. doi: 10.3389/fvets.2022.925773
6	HUYT,NGUYENT T,KIMH,et al.Brucella phagocytosis mediated by pathogen-host interactions and their intracellular survival[J].Microorganisms,2022,10(10):2003. doi: 10.3390/microorganisms10102003
7	COLOMA-RIVEROR F,FLORES-CONCHAM,MOLINAR E,et al.Brucella and its hidden flagellar system[J].Microorganisms,2021,10(1):83. doi: 10.3390/microorganisms10010083
8	ZHANGY,LIT,ZHANGJ,et al.The Brucella melitensis M5-90 phosphoglucomutase (PGM) mutant is attenuated and confers protection against wild-type challenge in BALB/c mice[J].World J Microbiol Biotechnol,2016,32(4):58. doi: 10.1007/s11274-016-2015-6
9	DORNELESE M,LIMAG K,TEIXEIRA-CARVALHOA,et al.Immune response of calves vaccinated with Brucella abortus S19 or RB51 and revaccinated with RB51[J].PLoS One,2015,10(9):e136696.
10	IVANOVA V,SALMAKOVK M,OLSENS C,et al.A live vaccine from Brucella abortus strain 82 for control of cattle brucellosis in the Russian federation[J].Anim Health Res Rev,2011,12(1):113-121. doi: 10.1017/S1466252311000028
11	RAMNANANA,CAMPBELLM,ASGARALIZ,et al.Experimental study on Brucella abortus strain RB51 vaccinated water buffalo (Bubalus bubalis) challenged with virulent B. abortus strain during pregnancy[J].J Buffalo Sci,2018,7(2):17-29. doi: 10.6000/1927-520X.2018.07.02.1
12	CHENGZ,LIZ,YINY,et al.Characteristics of Brucella abortus vaccine strain A19 reveals its potential mechanism of attenuated virulence[J].Vet Microbiol,2021,254,109007. doi: 10.1016/j.vetmic.2021.109007
13	WANGZ,WANGY,YANGH,et al.Doxycycline induces apoptosis of Brucella suis S2 strain-infected HMC3 microglial cells by activating calreticulin-dependent JNK/p53 signaling pathway[J].Front Cell Infect Microbiol,2021,11,640847. doi: 10.3389/fcimb.2021.640847
14	VIVES-SOTOM,PUERTA-GARCIAA,RODRIGUEZ-SANCHEZE,et al.What risk do Brucella vaccines pose to humans? A systematic review of the scientific literature on occupational exposure[J].PLoS Negl Trop Dis,2024,18(1):e11889.
15	KLINEK A,FÄLKERS,DAHLBERGS,et al.Bacterial adhesins in host-microbe interactions[J].Cell Host Microbe,2009,5(6):580-592. doi: 10.1016/j.chom.2009.05.011
16	CASTANEDA-ROLDANE I,OUAHRANI-BETTACHES,SALDANAZ,et al.Characterization of SP41, a surface protein of Brucella associated with adherence and invasion of host epithelial cells[J].Cell Microbiol,2006,8(12):1877-1887. doi: 10.1111/j.1462-5822.2006.00754.x
17	POSADASD M,RUIZ-RANWEZV,BONOMIH R,et al.BmaC, a novel autotransporter of Brucella suis, is involved in bacterial adhesion to host cells[J].Cell Microbiol,2012,14(6):965-982. doi: 10.1111/j.1462-5822.2012.01771.x
18	RUIZ-RANWEZV,POSADASD M,Van der HENSTC,et al.BtaE, an adhesin that belongs to the trimeric autotransporter family, is required for full virulence and defines a specific adhesive pole of Brucella suis[J].Infect Immun,2013,81(3):996-1007. doi: 10.1128/IAI.01241-12
19	RUIZ-RANWEZV,POSADASD M,ESTEINS M,et al.The BtaF trimeric autotransporter of Brucella suis is involved in attachment to various surfaces, resistance to serum and virulence[J].PLoS ONE,2013,8(11):e79770. doi: 10.1371/journal.pone.0079770
20	MUNOZG F,SYCZG,ALONSOP I,et al.The BtaF adhesin is necessary for full virulence during respiratory infection by Brucella suis and is a novel immunogen for nasal vaccination against Brucella infection[J].Front Immunol,2019,10,1775. doi: 10.3389/fimmu.2019.01775
21	CZIBENERC,MERWAISSF,GUAIMASF,et al.BigA is a novel adhesin of Brucella that mediates adhesion to epithelial cells[J].Cell Microbiol,2016,18(4):500-513. doi: 10.1111/cmi.12526
22	LEOJ C,OBERHETTINGERP,SCHÜTZM,et al.The inverse autotransporter family: Intimin, invasin and related proteins[J].Interl J Med Microbiol,2015,305(2):276-282. doi: 10.1016/j.ijmm.2014.12.011
23	LOPEZP,GUAIMASF,CZIBENERC,et al.A genomic island in Brucella involved in the adhesion to host cells: Identification of a new adhesin and a translocation factor[J].Cell Microbiol,2020,22(11):e13245.
24	BIALERM G,FERREROM C,DELPINOM V,et al.Adhesive functions or pseudogenization of type Va autotransporters in Brucella species[J].Front Cell Infect Microbiol,2021,11,607610. doi: 10.3389/fcimb.2021.607610
25	CELLI J. The intracellular life cycle of Brucella spp. [J/OL]. Microbiol Spectr, 2019, 7(2): 10.1128/microbiolspec. bai-0006-2019. [2025-01-20] https://doi.org/10.1128/microbiolspec.bai-0006-2019.
26	ROOPR N,BARTONI S,HOPERSBERGERD,et al.Uncovering the hidden credentials of Brucella virulence[J].Microbiol Mol Biol Rev,2021,85(1):e00021-19.
27	COMERCID J,MARTINEZ-LORENZOM J,SIEIRAR,et al.Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole[J].Cell Microbiol,2001,3(3):159-168. doi: 10.1046/j.1462-5822.2001.00102.x
28	PALOMARES-RESENDIZE,ARELLANO-REYNOSOB,HERNANDEZ-CASTROR,et al.Immunogenic response of Brucella canis virB10 and virB11 mutants in a murine model[J].Front Cell Infect Microbiol,2012,2,35.
29	MACEDOA A,SILVAA P,MOLJ P,et al.The abcEDCBA-encoded ABC transporter and the virB operon-encoded type Ⅳ secretion system of Brucella ovis are critical for intracellular trafficking and survival in ovine monocyte-derived macrophages[J].PLoS One,2015,10(9):e138131.
30	MYENIS,CHILDR,NGT W,et al.Brucella modulates secretory trafficking via multiple type Ⅳ secretion effector proteins[J].PLoS Pathog,2013,9(8):e1003556. doi: 10.1371/journal.ppat.1003556
31	MARCHESINIM I,HERRMANNC K,SALCEDOS P,et al.In search of Brucella abortus type Ⅳ secretion substrates: screening and identification of four proteins translocated into host cells through VirB system[J].Cell Microbiol,2011,13(8):1261-1274. doi: 10.1111/j.1462-5822.2011.01618.x
32	JABOULAYC,GODEUXA S,DOUBLETP,et al.Regulatory networks of the T4SS control: From host cell sensing to the biogenesis and the activity during the infection[J].J Mol Biol,2021,433(9):166892. doi: 10.1016/j.jmb.2021.166892
33	SALCEDOS P,MARCHESINIM I,DEGOSC,et al.BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions[J].Front Cell Infect Microbiol,2013,3,28.
34	DÖHMERP H,VALGUARNERAE,CZIBENERC,et al.Identification of a type Ⅳ secretion substrate of Brucella abortus that participates in the early stages of intracellular survival[J].Cell Microbiol,2014,16(3):396-410. doi: 10.1111/cmi.12224
35	杨琴,邓肖玉,谢珊珊,等.牛种布鲁氏菌Ⅳ型分泌系统对巨噬细胞内质网应激和细胞凋亡的影响[J].畜牧兽医学报,2022,53(4):1192-1200. doi: 10.11843/j.issn.0366-6964.2022.04.019
	YANGQ,DENGX Y,XIES S,et al.Effects of Brucella bovis type Ⅳ secretion system on endoplasmic reticulum stress and apoptosis of macrophages[J].Acta Veterinaria et Zootechnica Sinica,2022,53(4):1192-1200. doi: 10.11843/j.issn.0366-6964.2022.04.019
36	de JONGM F,SUNY H,den HARTIGHA B,et al.Identification of VceA and VceC, two members of the VjbR regulon that are translocated into macrophages by the Brucella type Ⅳ secretion system[J].Mol Microbiol,2008,70(6):1378-1396. doi: 10.1111/j.1365-2958.2008.06487.x
37	de JONGM F,STARRT,WINTERM G,et al.Sensing of bacterial type Ⅳ secretion via the unfolded protein response[J].mBio,2013,4(1):e412-e418.
38	ARRIOLAB P,REYS D,HERRMANNC K,et al.The effector protein BPE005 from Brucella abortus induces collagen deposition and matrix metalloproteinase 9 downmodulation via transforming growth factor beta1 in hepatic stellate cells[J].Infect Immun,2016,84(2):598-606. doi: 10.1128/IAI.01227-15
39	MARCHESINIM I,MORRONES S,GUAIMASF F,et al.A T4SS effector targets host cell alpha-enolase contributing to Brucella abortus intracellular lifestyle[J].Front Cell Infect Microbiol,2016,6,153.
40	de BARSYM,JAMETA,FILOPOND,et al.Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2[J].Cell Microbiol,2011,13(7):1044-1058. doi: 10.1111/j.1462-5822.2011.01601.x
41	KAMBAREVS,BORGHESANE,MILLERC N,et al.The Brucella abortus type Ⅳ effector BspA inhibits MARCH6-dependent ERAD to promote intracellular growth[J].Infect Immun,2023,91(5):e13023.
42	MILLERC N,SMITHE P,CUNDIFFJ A,et al.A Brucella type Ⅳ effector targets the COG tethering complex to remodel host secretory traffic and promote intracellular replication[J].Cell Host Microbe,2017,22(3):317-329. doi: 10.1016/j.chom.2017.07.017
43	BORGHESANE,SMITHE P,MYENIS,et al.A Brucella effector modulates the Arf6-Rab8a GTPase cascade to promote intravacuolar replication[J].EMBO J,2021,40(19):e107664. doi: 10.15252/embj.2021107664
44	LUIZETJ B,RAYMONDJ,LACERDAT,et al.The Brucella effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells[J].Proc Natl Acad Sci U S A,2021,118(32):e2105324118. doi: 10.1073/pnas.2105324118
45	MAZ,DENGX,LIR,et al.Crosstalk of Brucella abortus nucleomodulin BspG and host DNA replication process/mitochondrial respiratory pathway promote anti-apoptosis and infection[J].Vet Microbiol,2022,268,109414. doi: 10.1016/j.vetmic.2022.109414
46	MAZ,LIR,HUR,et al.Brucella abortus BspJ is a nucleomodulin that inhibits macrophage apoptosis and promotes intracellular survival of Brucella[J].Front Microbiol,2020,11,599205. doi: 10.3389/fmicb.2020.599205
47	LOUCHEA,BLANCOA,LACERDAT,et al.Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins[J].Nat Commun,2023,14(1):102. doi: 10.1038/s41467-022-35763-8
48	GIMÉNEZA,DEL GIUDICEM G,LÓPEZP V,et al.Brucella NpeA is a secreted type Ⅳ effector containing an N-WASP-binding short linear motif that promotes niche formation[J].mBio,2024,15(7):e0072624. doi: 10.1128/mbio.00726-24
49	徐朕宇,邓肖玉,王月丽,等.牛种布鲁氏菌A19ΔBtpA缺失株生物学特性及其免疫原性研究[J].畜牧兽医学报,2024,55(5):2135-2145. doi: 10.11843/j.issn.0366-6964.2024.05.031
	XUZ Y,DENGX Y,WANGY L,et al.Biological characteristics of Brucella abortus A19ΔBtpA deletion strain and its immunogenicity study[J].Acta Veterinaria et Zootechnica Sinica,2024,55(5):2135-2145. doi: 10.11843/j.issn.0366-6964.2024.05.031
50	ZSCHIEDRICHC P,KEIDELV,SZURMANTH.Molecular mechanisms of two-component signal transduction[J].J Mol Biol,2016,428(19):3752-3775. doi: 10.1016/j.jmb.2016.08.003
51	GUZMAN-VERRIC,MANTEROLAL,SOLA-LANDAA,et al.The two-component system BvrR/BvrS essential for Brucella abortus virulence regulates the expression of outer membrane proteins with counterparts in members of the Rhizobiaceae[J].Proc Natl Acad Sci U S A,2002,99(19):12375-12380. doi: 10.1073/pnas.192439399
52	STERNONJ F,GODESSARTP,GONCALVESD F R,et al.Transposon sequencing of Brucella abortus uncovers essential genes for growth in vitro and inside macrophages[J].Infect Immun,2018,86(8):e00312-18.
53	KOHLERS,FOULONGNEV,OUAHRANI-BETTACHES,et al.The analysis of the intramacrophagic virulome of Brucella suis deciphers the environment encountered by the pathogen inside the macrophage host cell[J].Proc Natl Acad Sci U S A,2002,99(24):15711-15716. doi: 10.1073/pnas.232454299
54	ALTAMIRANO-SILVAP,MEZA-TORRESJ,CASTILLO-ZELEDONA,et al.Brucella abortus senses the intracellular environment through the BvrR/BvrS two-component system, which allows B. abortus to adapt to its replicative niche[J].Infect Immun,2018,86(4):e00713-17.
55	ALTAMIRANO-SILVAP,CORDERO-SERRANOM,MENDEZ-MONTOYAJ,et al.Intracellular passage triggers a molecular response in Brucella abortus that increases its infectiousness[J].Infect Immun,2021,89(7):e421.
56	FONTANAC,CONDE-ALVAREZR,STAHLEJ,et al.Structural studies of lipopolysaccharide-defective mutants from Brucella melitensis identify a core oligosaccharide critical in virulence[J].J Biol Chem,2016,291(14):7727-7741. doi: 10.1074/jbc.M115.701540
57	MARTINEZ-NUNEZC,ALTAMIRANO-SILVAP,ALVARADO-GUILLENF,et al.The two-component system BvrR/BvrS regulates the expression of the type Ⅳ secretion system VirB in Brucella abortus[J].J Bacteriol,2010,192(21):5603-5608. doi: 10.1128/JB.00567-10
58	BIALERM G,RUIZ-RANWEZV,SYCZG,et al.MapB, the Brucella suis TamB homologue, is involved in cell envelope biogenesis, cell division and virulence[J].Sci Rep,2019,9(1):2158. doi: 10.1038/s41598-018-37668-3
59	RIVAS-SOLANOO,Van der HENSTM,CASTILLO-ZELEDONA,et al.The regulon of Brucella abortus two-component system BvrR/BvrS reveals the coordination of metabolic pathways required for intracellular life[J].PLoS One,2022,17(9):e274397.
60	SOLA-LANDAA,PIZARRO-CERDAJ,GRILLOM J,et al.A two-component regulatory system playing a critical role in plant pathogens and endosymbionts is present in Brucella abortus and controls cell invasion and virulence[J].Mol Microbiol,1998,29(1):125-138. doi: 10.1046/j.1365-2958.1998.00913.x
61	CARRICAM D C,FERNANDEZI,MARTÍM A,et al.The NtrY/X two-component system of Brucella spp. acts as a redox sensor and regulates the expression of nitrogen respiration enzymes[J].Mol Microbiol,2012,85(1):39-50. doi: 10.1111/j.1365-2958.2012.08095.x
62	FOULONGNEV,BOURGG,CAZEVIEILLEC,et al.Identification of Brucella suis genes affecting intracellular survival in an in vitro human macrophage infection model by signature-tagged transposon mutagenesis[J].Infect Immun,2000,68(3):1297-1303. doi: 10.1128/IAI.68.3.1297-1303.2000
63	ELSENS,SWEML R,SWEMD L,et al.RegB/RegA, a highly conserved redox-responding global two-component regulatory system[J].Microbiol Mol Biol Rev,2004,68(2):263-279. doi: 10.1128/MMBR.68.2.263-279.2004
64	ABDOUE,DEREDJIANA,JIMÉNEZ DE BAGÜÉSM P,et al.RegA, the regulator of the two-component system RegB/RegA of Brucella suis, is a controller of both oxidative respiration and denitrification required for chronic infection in mice[J].Infect Immun,2013,81(6):2053-2061. doi: 10.1128/IAI.00063-13
65	DUDDYO P,BASSLERB L.Quorum sensing across bacterial and viral domains[J].PLoS Pathog,2021,17(1):e1009074. doi: 10.1371/journal.ppat.1009074
66	MUKHERJEES,BASSLERB L.Bacterial quorum sensing in complex and dynamically changing environments[J].Nat Rev Microbiol,2019,17(6):371-382. doi: 10.1038/s41579-019-0186-5
67	LIS,WUS,RENY,et al.Characterization of differentiated autoregulation of LuxI/LuxR-type quorum sensing system in Pseudoalteromonas[J].Biochem Biophys Res Commun,2022,590,177-183. doi: 10.1016/j.bbrc.2021.12.107
68	TAMINIAUB,DAYKINM,SWIFTS,et al.Identification of a quorum-sensing signal molecule in the facultative intracellular pathogen Brucella melitensis[J].Infect Immun,2002,70(6):3004-3011. doi: 10.1128/IAI.70.6.3004-3011.2002
69	DELRUER M,DESCHAMPSC,LEONARDS,et al.A quorum-sensing regulator controls expression of both the type Ⅳ secretion system and the flagellar apparatus of Brucella melitensis[J].Cell Microbiol,2005,7(8):1151-1161. doi: 10.1111/j.1462-5822.2005.00543.x
70	RAMBOW-LARSENA A,RAJASHEKARAG,PETERSENE,et al.Putative quorum-sensing regulator BlxR of Brucella melitensis regulates virulence factors including the type Ⅳ secretion system and flagella[J].J Bacteriol,2008,190(9):3274-3282. doi: 10.1128/JB.01915-07
71	LAPAQUEN,MORIYONI,MORENOE,et al.Brucella lipopolysaccharide acts as a virulence factor[J].Curr Opin Microbiol,2005,8(1):60-66. doi: 10.1016/j.mib.2004.12.003
72	PORTEF,NAROENIA,OUAHRANI-BETTACHES,et al.Role of the Brucella suis lipopolysaccharide O antigen in phagosomal genesis and in inhibition of phagosome-lysosome fusion in murine macrophages[J].Infect Immun,2003,71(3):1481-1490. doi: 10.1128/IAI.71.3.1481-1490.2003
73	NAROENIA,PORTEF.Role of cholesterol and the ganglioside GM(1) in entry and short-term survival of Brucella suis in murine macrophages[J].Infect Immun,2002,70(3):1640-1644. doi: 10.1128/IAI.70.3.1640-1644.2002
74	CHENF,HEY.Caspase-2 mediated apoptotic and necrotic murine macrophage cell death induced by rough Brucella abortus[J].PLoS One,2009,4(8):e6830. doi: 10.1371/journal.pone.0006830
75	BRYANTC E,SPRINGD R,GANGLOFFM,et al.The molecular basis of the host response to lipopolysaccharide[J].Nat Rev Microbiol,2010,8(1):8-14. doi: 10.1038/nrmicro2266
76	BARQUERO-CALVOE,CHAVES-OLARTEE,WEISSD S,et al.Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection[J].PLoS One,2007,2(7):e631. doi: 10.1371/journal.pone.0000631
77	LAPAQUEN,TAKEUCHIO,CORRALESF,et al.Differential inductions of TNF-α and IGTP, ⅡGP by structurally diverse classic and non-classic lipopolysaccharides[J].Cell Microbiol,2006,8(3):401-413. doi: 10.1111/j.1462-5822.2005.00629.x
78	ZYGMUNTM S,BLASCOJ M,LETESSONJ J,et al.DNA polymorphism analysis of Brucella lipopolysaccharide genes reveals marked differences in O-polysaccharide biosynthetic genes between smooth and rough Brucella species and novel species-specific markers[J].BMC Microbiol,2009,9,92. doi: 10.1186/1471-2180-9-92
79	ALLENC A,ADAMSL G,FICHTT A.Transposon-derived Brucella abortus rough mutants are attenuated and exhibit reduced intracellular survival[J].Infect Immun,1998,66(3):1008-1016. doi: 10.1128/IAI.66.3.1008-1016.1998
80	MCQUISTONJ R,VEMULAPALLIR,INZANAT J,et al.Genetic characterization of a Tn5-disrupted glycosyltransferase gene homolog in Brucella abortus and its effect on lipopolysaccharide composition and virulence[J].Infect Immun,1999,67(8):3830-3835. doi: 10.1128/IAI.67.8.3830-3835.1999
81	GODFROIDF,TAMINIAUB,DANESEI,et al.Identification of the perosamine synthetase gene of Brucella melitensis 16M and involvement of lipopolysaccharide O side chain in Brucella survival in mice and in macrophages[J].Infect Immun,1998,66(11):5485-5493. doi: 10.1128/IAI.66.11.5485-5493.1998
82	VALGUARNERAE,SPERAJ M,CZIBENERC,et al.RomA, a periplasmic protein involved in the synthesis of the lipopolysaccharide, tunes down the inflammatory response triggered by Brucella[J].J Infect Dis,2018,217(8):1257-1266. doi: 10.1093/infdis/jiy002
83	SALVADOR-BESCÓSM,GIL-RAMÍREZY,ZÚÑIGA-RIPAA,et al.WadD, a new Brucella lipopolysaccharide core glycosyltransferase identified by genomic search and phenotypic characterization[J].Front Microbiol,2018,9,2293. doi: 10.3389/fmicb.2018.02293
84	BONTEMPS-GALLOS,LACROIXJ M.New insights into the biological role of the osmoregulated periplasmic glucans in pathogenic and symbiotic bacteria[J].Environ Microbiol Rep,2015,7(5):690-697. doi: 10.1111/1758-2229.12325
85	BREEDVELDM W,MILLERK J.Cyclic β-glucans of members of the family Rhizobiaceae[J].Microbiol Rev,1994,58(2):145-161. doi: 10.1128/mr.58.2.145-161.1994
86	BRIONESG,de LANNINON I,STEINBERGM,et al.Periplasmic cyclic 1, 2-β-glucan in Brucella spp. is not osmoregulated[J].Microbiology (Reading),1997,143(Pt 4):1115-1124.
87	BRIONESG,INOND I N,ROSETM,et al.Brucella abortus cyclicβ-1, 2-glucan mutants have reduced virulence in mice and are defective in intracellular replication in HeLa cells[J].Infect Immun,2001,69(7):4528-4535. doi: 10.1128/IAI.69.7.4528-4535.2001
88	ARELLANO-REYNOSOB,LAPAQUEN,SALCEDOS,et al.Cyclicβ-1, 2-glucan is a Brucella virulence factor required for intracellular survival[J].Nat Immunol,2005,6(6):618-625. doi: 10.1038/ni1202
89	DEGOSC,GAGNAIREA,BANCHEREAUR,et al.Brucella CβG induces a dual pro-and anti-inflammatory response leading to a transient neutrophil recruitment[J].Virulence,2014,6(1):19-28.
90	MARTIROSYANA,PÉREZ-GUTIERREZC,BANCHEREAUR,et al.Brucella β 1, 2 cyclic glucan is an activator of human and mouse dendritic cells[J].PLoS Pathog,2012,8(11):e1002983. doi: 10.1371/journal.ppat.1002983
91	ROSETM S,IBAÑEZA E,de SOUZA FILHOJ A,et al.Brucella cyclic β-1, 2-glucan plays a critical role in the induction of splenomegaly in mice[J].PLoS ONE,2014,9(7):e101279. doi: 10.1371/journal.pone.0101279
92	ZHENGW Y,WANGY,ZHANGZ C,et al.Immunological characteristics of outer membrane protein omp31 of goat Brucella and its monoclonal antibody[J].Genet Mol Res,2015,14(4):11965-11974. doi: 10.4238/2015.October.5.10
93	MARTIN-MARTINA I,SANCHOP,TEJEDORC,et al.Differences in the outer membrane-related properties of the six classical Brucella species[J].Vet J,2011,189(1):103-105. doi: 10.1016/j.tvjl.2010.05.021
94	CARO-HERNANDEZP,FERNANDEZ-LAGOL,de MIGUELM J,et al.Role of the Omp25/Omp31 family in outer membrane properties and virulence of Brucella ovis[J].Infect Immun,2007,75(8):4050-4061. doi: 10.1128/IAI.00486-07
95	VERDIGUEL-FERNANDEZL,OROPEZA-NAVARROR,ORTIZA,et al.Brucella melitensis omp31 mutant is attenuated and confers protection against virulent Brucella melitensis challenge in BALB/c mice[J].J Microbiol Biotechnol,2020,30(4):497-504. doi: 10.4014/jmb.1908.08056
96	VERDIGUEL-FERNANDEZL,OROPEZA-NAVARROR,BASURTO-ALCANTARAF J,et al.Omp31 plays an important role on outer membrane properties and intracellular survival of Brucella melitensis in murine macrophages and HeLa cells[J].Arch Microbiol,2017,199(7):971-978. doi: 10.1007/s00203-017-1360-7
97	ZHANGK,WANGH,GUOF,et al.OMP31 of Brucella Melitensis 16M impairs the apoptosis of macrophages triggered by TNF-alpha[J].Exp Ther Med,2016,12(4):2783-2789. doi: 10.3892/etm.2016.3655
98	LIR,LIUW,YINX,et al.Brucella spp. Omp25 promotes proteasome-mediated cGAS degradation to attenuate IFN-beta production[J].Front Microbiol,2021,12,702881. doi: 10.3389/fmicb.2021.702881
99	DEGOSC,HYSENAJL,GONZALEZ-ESPINOZAG,et al.Omp25-dependent engagement of SLAMF1 by Brucella abortus in dendritic cells limits acute inflammation and favours bacterial persistence in vivo[J].Cell Microbiol,2020,22(4):e13164.
100	PASQUEVICHK A,CARABAJALM V,GUAIMASF F,et al.Omp19 enables Brucella abortus to evade the antimicrobial activity from host's proteolytic defense system[J].Front Immunol,2019,10,1436. doi: 10.3389/fimmu.2019.01436
101	ZHIF,ZHOUD,LIJ,et al.Omp16, a conserved peptidoglycan-associated lipoprotein, is involved in Brucella virulence in vitro[J].J Microbiol,2020,58(9):793-804. doi: 10.1007/s12275-020-0144-y
102	李杨,周栋,尹彦龙,等.布鲁氏菌OMP16对RAW264.7细胞凋亡与免疫活性的影响[J].畜牧兽医学报,2022,53(8):2642-2651. doi: 10.11843/j.issn.0366-6964.2022.08.022
	LIY,ZHOUD,YINY L,et al.Effects of Brucella outer membrane protein 16 on apoptosis and immune activity of RAW264.7 cells[J].Acta Veterinaria et Zootechnica Sinica,2022,53(8):2642-2651. doi: 10.11843/j.issn.0366-6964.2022.08.022
103	HALLINGS M.On the presence and organization of open reading frames of the nonmotile pathogen Brucella abortus similar to class Ⅱ, Ⅲ, and Ⅳ flagellar genes and to LcrD virulence superfamily[J].Microb Comp Genomics,1998,3(1):21-29. doi: 10.1089/omi.1.1998.3.21
104	DELVECCHIOV G,KAPATRALV,REDKARR J,et al.The genome sequence of the facultative intracellular pathogen Brucella melitensis[J].Proc Natl Acad Sci U S A,2002,99(1):443-448. doi: 10.1073/pnas.221575398
105	FRETIND,FAUCONNIERA,KÖHLERS,et al.The sheathed flagellum of Brucella melitensis is involved in persistence in a murine model of infection[J].Cell Microbiol,2005,7(5):687-698. doi: 10.1111/j.1462-5822.2005.00502.x
106	ALD S,KOHLERS,OCCHIALINIA,et al.Brucella spp. of amphibians comprise genomically diverse motile strains competent for replication in macrophages and survival in mammalian hosts[J].Sci Rep,2017,1,44420.
107	LESTRATEP,DRICOTA,DELRUER M,et al.Attenuated signature-tagged mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice[J].Infect Immun,2003,71(12):7053-7060. doi: 10.1128/IAI.71.12.7053-7060.2003
108	ZYGMUNTM S,HAGIUSS D,WALKERJ V,et al.Identification of Brucella melitensis 16M genes required for bacterial survival in the caprine host[J].Microbes Infect,2006,8(14-15):2849-2854. doi: 10.1016/j.micinf.2006.09.002
109	TERWAGNEM,FEROOZJ,ROLANH G,et al.Innate immune recognition of flagellin limits systemic persistence of Brucella[J].Cell Microbiol,2013,15(6):942-960. doi: 10.1111/cmi.12088
110	HUGI,DESHPANDES,SPRECHERK S,et al.Second messenger-mediated tactile response by a bacterial rotary motor[J].Science,2017,358(6362):531-534. doi: 10.1126/science.aan5353
111	ELLISONC K,KANJ,DILLARDR S,et al.Obstruction of pilus retraction stimulates bacterial surface sensing[J].Science,2017,358(6362):535-538. doi: 10.1126/science.aan5706
112	ASCHTGENM S,LYNCHJ B,KOCHE,et al.Rotation of Vibrio fischeri flagella produces outer membrane vesicles that induce host development[J].J Bacteriol,2016,198(16):2156-2165. doi: 10.1128/JB.00101-16
113	UZUREAUS,LEMAIREJ,DELAIVEE,et al.Global analysis of quorum sensing targets in the intracellular pathogen Brucella melitensis 16 M[J].J Proteome Res,2010,9(6):3200-3217. doi: 10.1021/pr100068p
114	GOURLEYC R,PETERSENE,HARMSJ,et al.Decreased in vivo virulence and altered gene expression by a Brucella melitensis light-sensing histidine kinase mutant[J].Pathog Dis,2015,73(2):1-8.
115	FEROOZJ,LEMAIREJ,DELORYM,et al.RpoE1, an extracytoplasmic function sigma factor, is a repressor of the flagellar system in Brucella melitensis[J].Microbiology (Reading),2011,157(Pt 5):1263-1268.
116	KIMH S,CASWELLC C,FOREMANR,et al.The Brucella abortus general stress response system regulates chronic mammalian infection and is controlled by phosphorylation and proteolysis[J].J Biol Chem,2013,288(19):13906-13916. doi: 10.1074/jbc.M113.459305
117	YANX,HUS,YANGY,et al.The twin-arginine translocation system is important for stress resistance and virulence of Brucella melitensis[J].Infect Immun,2020,88(11):e00389-20.
118	SUND,LIUY,PENGX,et al.ClpP protease modulates bacterial growth, stress response, and bacterial virulence in Brucella abortus[J].Vet Res,2023,54(1):68. doi: 10.1186/s13567-023-01200-x
119	DRAZEKE S,HOUNGH S,CRAWFORDR M,et al.Deletion of purE attenuates Brucella melitensis 16M for growth in human monocyte-derived macrophages[J].Infect Immun,1995,63(9):3297-3301. doi: 10.1128/iai.63.9.3297-3301.1995
120	TRUONGQ L,CHOY,BARATEA K,et al.Mutation of purD and purF genes further attenuates Brucella abortus strain RB51[J].Microb Pathog,2015,79,1-7. doi: 10.1016/j.micpath.2014.12.003
121	MARCHESINIM I,SPERAJ M,COMERCID J.The 'ins and outs' of Brucella intracellular journey[J].Curr Opin Microbiol,2024,78,102427. doi: 10.1016/j.mib.2024.102427
122	STARRT,CHILDR,WEHRLYT D,et al.Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle[J].Cell Host Microbe,2012,11(1):33-45. doi: 10.1016/j.chom.2011.12.002
123	VON BARGENK,GORVELJ P,SALCEDOS P.Internal affairs: investigating the Brucella intracellular lifestyle[J].FEMS Microbiol Rev,2012,36(3):533-562. doi: 10.1111/j.1574-6976.2012.00334.x
124	SEDZICKIJ,TSCHONT,LOWS H,et al.3D correlative electron microscopy reveals continuity of Brucella-containing vacuoles with the endoplasmic reticulum[J].J Cell Sci,2018,131(4):jcs210799. doi: 10.1242/jcs.210799
125	JIAOH,ZHOUZ,LIB,et al.The mechanism of facultative intracellular parasitism of Brucella[J].Int J Mol Sci,2021,22(7):3673. doi: 10.3390/ijms22073673
126	STRANAHANL W,ARENAS-GAMBOAA M.When the going gets rough: the significance of Brucella lipopolysaccharide phenotype in host-pathogen interactions[J].Front Microbiol,2021,12,713157. doi: 10.3389/fmicb.2021.713157
127	ANDERSEN-NISSENE,SMITHK D,STROBEK L,et al.Evasion of Toll-like receptor 5 by flagellated bacteria[J].Proc Natl Acad Sci U S A,2005,102(26):9247-9252. doi: 10.1073/pnas.0502040102
128	VELASQUEZL N,MILILLOM A,DELPINOM V,et al.Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway[J].Immunol Cell Biol,2017,95(4):388-398. doi: 10.1038/icb.2016.111
129	KHANM,HARMSJ S,LIUY,et al.Brucella suppress STING expression via miR-24 to enhance infection[J].PLoS Pathog,2020,16(10):e1009020. doi: 10.1371/journal.ppat.1009020
130	LIW,KEY,WANGY,et al.Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection[J].Biochem Biophys Res Commun,2016,477(3):509-514. doi: 10.1016/j.bbrc.2016.06.064
131	席静,王月丽,邓肖玉,等.STAT6介导的巨噬细胞极化对布鲁氏菌胞内存活的影响[J].畜牧兽医学报,2022,53(1):263-271. doi: 10.11843/j.issn.0366-6964.2022.01.026
	XIJ,WANGY L,DENGX Y,et al.Effect of STAT6 mediated macrophage polarization on intracellular survival of Brucella[J].Acta Veterinaria et Zootechnica Sinica,2022,53(1):263-271. doi: 10.11843/j.issn.0366-6964.2022.01.026
132	WANGY,XIJ,YIJ,et al.Brucella induces M1 to M2 polarization of macrophages through STAT6 signaling pathway to promote bacterial intracellular survival[J].Res Vet Sci,2022,145,91-101. doi: 10.1016/j.rvsc.2022.02.006
133	HELLERM C,WATSONJ L,BLANCHARDM T,et al.Characterization of Brucella abortus infection of bovine monocyte-derived dendritic cells[J].Vet Immunol Immunopathol,2012,149(3-4):255-261. doi: 10.1016/j.vetimm.2012.07.006
134	SALCEDOS P,MARCHESINIM I,LELOUARDH,et al.Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1[J].PLoS Pathog,2008,4(2):e21. doi: 10.1371/journal.ppat.0040021
135	BILLARDE,DORNANDJ,GROSSA.Brucella suis prevents human dendritic cell maturation and antigen presentation through regulation of tumor necrosis factor alpha secretion[J].Infect Immun,2007,75(10):4980-4989. doi: 10.1128/IAI.00637-07
136	LEIC Q,WUX,ZHONGX,et al.USP19 inhibits TNF-α- and IL-1β-triggered NF-κB activation by deubiquitinating TAK1[J].J Immunol,2019,203(1):259-268. doi: 10.4049/jimmunol.1900083
137	YANGX,HEZ,ZHANGG,et al.Evaluation of reactivity of monoclonal antibodies against Omp25 of Brucella spp[J].Front Cell Infect Microbiol,2020,10,145. doi: 10.3389/fcimb.2020.00145
138	LUOX,ZHANGX,WUX,et al.Brucella downregulates tumor necrosis factor-α to promote intracellular survival via Omp25 regulation of different microRNAs in porcine and murine macrophages[J].Front Immunol,2017,8,2013.
139	ZHANGJ,ZHANGY,LIZ,et al.Outer membrane protein 25 of Brucella activates mitogen-activated protein kinase signal pathway in human trophoblast cells[J].Front Vet Sci,2017,4,197. doi: 10.3389/fvets.2017.00197
140	BAIQ,LIH,WUX,et al.Comparative analysis of the main outer membrane proteins of Brucella in the diagnosis of brucellosis[J].Biochem Biophys Res Commun,2021,560,126-131. doi: 10.1016/j.bbrc.2021.04.127
141	WANGZ,WANGG,WANGY,et al.Omp31 of Brucella inhibits NF-κB p65 signaling pathway by inducing autophagy in BV-2 microglia[J].Neurochem Res,2021,46(12):3264-3272. doi: 10.1007/s11064-021-03429-4
142	SPERAJ M,UGALDEJ E,MUCCIJ,et al.A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection[J].Proc Natl Acad Sci U S A,2006,103(44):16514-16519. doi: 10.1073/pnas.0603362103
143	SPERAJ M,HERRMANNC K,ROSETM S,et al.A Brucella virulence factor targets macrophages to trigger B-cell proliferation[J].J Biol Chem,2013,288(28):20208-20216. doi: 10.1074/jbc.M113.453282
144	SPERAJ M,COMERCID J,UGALDEJ E.Brucella alters the immune response in a prpA-dependent manner[J].Microb Pathog,2014,67(67-68):8-13.
145	SPERAJ M,GUAIMASF,CORVIM M,et al.Brucella hijacks host-mediated palmitoylation to stabilize and localize PrpA to the plasma membrane[J].Infect Immun,2018,86(11):e00402-18.
146	BRONNERD N,O'RIORDANM X,HEY.Caspase-2 mediates a Brucella abortus RB51-induced hybrid cell death having features of apoptosis and pyroptosis[J].Front Cell Infect Microbiol,2013,3,83.
147	WEIP,CUIG,LUQ,et al.A20 promotes Brucella intracellular growth via inhibition of macrophage cell death and activation[J].Vet Microbiol,2015,175(1):50-57. doi: 10.1016/j.vetmic.2014.11.006
148	ZHIF,ZHOUD,BAIF,et al.VceC mediated IRE1 pathway and inhibited CHOP-induced apoptosis to support Brucella replication in goat trophoblast cells[J].Int J Mol Sci,2019,20(17)
149	相彩霞,王相国,李俊玫,等.布鲁氏菌Ⅳ型分泌系统效应蛋白VceC对山羊滋养层细胞内质网应激和性腺激素分泌的影响[J].畜牧兽医学报,2023,54(3):1210-1220. doi: 10.11843/j.issn.0366-6964.2023.03.032
	XIANGC X,WANGX G,LIJ M,et al.The influence of Brucella type Ⅳ secretes system effector protein VceC on endoplasmic reticulum stress and gonadal hormone secretory in goat trophoblast cells[J].Acta Veterinaria et Zootechnica Sinica,2023,54(3):1210-1220. doi: 10.11843/j.issn.0366-6964.2023.03.032
150	HSUS K,LIC Y,LINI L,et al.Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment[J].Theranostics,2021,11(18):8813-8835. doi: 10.7150/thno.62521
151	KARMAKARM,MINNSM,GREENBERGE N,et al.N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis[J].Nat Commun,2020,11(1):2212. doi: 10.1038/s41467-020-16043-9
152	SHIH,GAOY,DONGZ,et al.GSDMD-mediated cardiomyocyte pyroptosis promotes myocardial I/R injury[J].Circ Res,2021,129(3):383-396. doi: 10.1161/CIRCRESAHA.120.318629
153	COSTA FRANCOM M S,MARIMF M,ALVES-SILVAJ,et al.AIM2 senses Brucella abortus DNA in dendritic cells to induce IL-1β secretion, pyroptosis and resistance to bacterial infection in mice[J].Microbes Infect,2019,21(2):85-93. doi: 10.1016/j.micinf.2018.09.001
154	LACEYC A,MITCHELLW J,DADELAHIA S,et al.Caspase-1 and Caspase-11 mediate pyroptosis, inflammation, and control of Brucella joint infection[J].Infect Immun,2018,86(9):e00361-18.
155	TUPIKJ D,COUTERMARSH-OTTS L,BENTONA H,et al.ASC-mediated inflammation and pyroptosis attenuates Brucella abortus pathogenesis following the recognition of gDNA[J].Pathogens,2020,9(12):1008. doi: 10.3390/pathogens9121008
156	MARIMF M,FRANCOM,GOMESM,et al.The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection[J].Semin Immunopathol,2017,39(2):215-223. doi: 10.1007/s00281-016-0581-1
157	JAKKAP,NAMANIS,MURUGANS,et al.The Brucella effector protein TcpB induces degradation of inflammatory caspases and thereby subverts non-canonical inflammasome activation in macrophages[J].J Biol Chem,2017,292(50):20613-20627. doi: 10.1074/jbc.M117.815878
158	CANTONM,SANCHEZ-RODRIGUEZR,SPERAI,et al.Reactive oxygen species in macrophages: sources and targets[J].Front Immunol,2021,12,734229. doi: 10.3389/fimmu.2021.734229
159	PRATTA J,DIDONATOM,SHIND S,et al.Structural, functional, and immunogenic insights on Cu, Zn superoxide dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus[J].J Bacteriol,2015,197(24):3834-3847. doi: 10.1128/JB.00343-15
160	MARTIND W,BAUMGARTNERJ E,GEEJ M,et al.SodA is a major metabolic antioxidant in Brucella abortus 2308 that plays a significant, but limited, role in the virulence of this strain in the mouse model[J].Microbiology (Reading),2012,158(Pt 7):1767-1774.
161	GEEJ M,VALDERASM W,KOVACHM E,et al.The Brucella abortus Cu, Zn superoxide dismutase is required for optimal resistance to oxidative killing by murine macrophages and wild-type virulence in experimentally infected mice[J].Infect Immun,2005,7 3(5):2873-2880.
162	IMLAYJ A.Cellular defenses against superoxide and hydrogen peroxide[J].Annu Rev Biochem,2008,77(1):755-776. doi: 10.1146/annurev.biochem.77.061606.161055
163	SHAZ,STABELT J,MAYFIELDJ E.Brucella abortus catalase is a periplasmic protein lacking a standard signal sequence[J].J Bacteriol,1994,176(23):7375-7377. doi: 10.1128/jb.176.23.7375-7377.1994
164	STEELEK H,BAUMGARTNERJ E,VALDERASM W,et al.Comparative study of the roles of AhpC and KatE as respiratory antioxidants in Brucella abortus 2308[J].J Bacteriol,2010,192(19):4912-4922. doi: 10.1128/JB.00231-10
165	KIMJ A,MAYFIELDJ.Identification of Brucella abortus OxyR and its role in control of catalase expression[J].J Bacteriol,2000,182(19):5631-5633. doi: 10.1128/JB.182.19.5631-5633.2000
166	SANGARIF J,CAYÓNA M,SEOANEA,et al.Brucella abortus ure2 region contains an acid-activated urea transporter and a nickel transport system[J].BMC Microbiol,2010,10,107. doi: 10.1186/1471-2180-10-107
167	SELEEMM N,BOYLES M,SRIRANGANATHANN.Brucella: a pathogen without classic virulence genes[J].Vet Microbiol,2008,129(1-2):1-14. doi: 10.1016/j.vetmic.2007.11.023
168	PAIXAOT A,ROUXC M,den HARTIGHA B,et al.Establishment of systemic Brucella melitensis infection through the digestive tract requires urease, the type Ⅳ secretion system, and lipopolysaccharide O antigen[J].Infect Immun,2009,77(10):4197-4208. doi: 10.1128/IAI.00417-09
169	LOISEL-MEYERS,JIMENEZD B M,KOHLERS,et al.Differential use of the two high-oxygen-affinity terminal oxidases of Brucella suis for in vitro and intramacrophagic multiplication[J].Infect Immun,2005,73(11):7768-7771. doi: 10.1128/IAI.73.11.7768-7771.2005
170	ENDLEYS,MCMURRAYD,FICHTT A.Interruption of the cydB locus in Brucella abortus attenuates intracellular survival and virulence in the mouse model of infection[J].J Bacteriol,2001,183(8):2454-2462. doi: 10.1128/JB.183.8.2454-2462.2001
171	BUENOE,MESAS,BEDMARE J,et al.Bacterial adaptation of respiration from oxic to microoxic and anoxic conditions: redox control[J].Antioxid Redox Signal,2012,16(8):819-852. doi: 10.1089/ars.2011.4051
172	HAINEV,DOZOTM,DORNANDJ,et al.NnrA is required for full virulence and regulates several Brucella melitensis denitrification genes[J].J Bacteriol,2006,188(4):1615-1619. doi: 10.1128/JB.188.4.1615-1619.2006
173	KIMD H,LIMJ J,LEEJ J,et al.Identification of genes contributing to the intracellular replication of Brucella abortus within HeLa and RAW 264.7 cells[J].Vet Microbiol,2012,158(3-4):322-328. doi: 10.1016/j.vetmic.2012.02.019
174	LOISEL-MEYERS,JIMÉNEZ D E BAGÜÉSM P,et al.Requirement of norD for Brucella suis virulence in a murine model of in vitroand in vivo infection[J].Infect Immun,2006,74(3):1973-1976. doi: 10.1128/IAI.74.3.1973-1976.2006
175	WANGM,QURESHIN,SOEURTN,et al.High levels of nitric oxide production decrease early but increase late survival of Brucella abortus in macrophages[J].Microb Pathog,2001,31(5):221-230. doi: 10.1006/mpat.2001.0463
176	LAMONTAGNEJ,FORESTA,MARAZZOE,et al.Intracellular adaptation of Brucella abortus[J].J Proteome Res,2009,8(3):1594-1609. doi: 10.1021/pr800978p
177	WEEKSJ N,GALINDOC L,DRAKEK L,et al.Brucella melitensis VjbR and C12-HSL regulons: contributions of the N-dodecanoyl homoserine lactone signaling molecule and LuxR homologue VjbR to gene expression[J].BMC Microbiol,2010,10,167. doi: 10.1186/1471-2180-10-167

效应蛋白 Effector protein	B. abortus中的开放阅读框 Open reading frames in B. abortus	氨基酸数 Amino acid number	宿主靶标 Target of host	功能 Function	方法 Method	参考文献 Reference
RicA	BAB1_1279	175	Rab2	调控囊泡运输	TEM1	[40]
VceA	BAB1_1652	105	未知	未知	CyaA，TEM1	[36]
VceC	BAB1_1058	418	Bip/Grp78	激活未折叠蛋白反应	CyaA，TEM1	[37]
BPE005	BAB1_2005	153	未知	未知	CyaA	[31]
BPE043	BAB1_1043	1553	未知	未知	CyaA	[31]
BPE275	BAB1_1275	253	未知	未知	CyaA	[31]
BPE123	BAB1_0123	153	未知	未知	CyaA	[31]
BtpA/TcpB/Btp1	BAB1_0279	250	MAL	抑制TLR通路	CyaA	[33, 49]
BtpB	BAB1_0756	292	未知	抑制TLR通路	CyaA，TEM1	[33]
BspA	BAB1_0678	191	未知	抑制分泌通路	CyaA，TEM1	[30]
BspB	BAB1_0712	187	未知	抑制分泌通路	CyaA，TEM1	[30]
BspC	BAB1_0847	137	未知	未知	CyaA，TEM1	[30]
BspE	BAB1_1671	117	未知	未知	CyaA，TEM1	[30]
BspF	BAB1_1948	428	未知	抑制分泌通路	CyaA，TEM1	[30]
SepA	BAB1_1492	130	未知	抑制BCV与溶酶体融合	CyaA，TEM1	[34]
NyxA	BAB1_0296	129	SENP3	抑制SENP3核定位	TEM1	[47]
NyxB	BAB1_1101	90	SENP3	抑制SENP3核定位	TEM1	[47]
NpeA	BAB2_0195	223	N-WASP	促进增殖憩室形成	In-silico analysis	[48]

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