{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:54:07Z","timestamp":1791500047955,"version":"4.3.4"},"reference-count":84,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brucellosis is a highly prevalent zoonotic disease caused by Brucella. Brucella spp. are gram-negative facultative intracellular parasitic bacteria. Its intracellular survival and replication depend on a functional virB system, an operon encoded by VirB1\u2013VirB12. Type IV secretion system (T4SS) encoded by the virB operon is an important virulence factor of Brucella. It can subvert cellular pathway and induce host immune response by secreting effectors, which promotes Brucella replication in host cells and induce persistent infection. Therefore, this paper summarizes the function and significance of the VirB system, focusing on the structure of the VirB system where VirB T4SS mediates biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV), the effectors of T4SS and the cellular pathways it subverts, which will help better understand the pathogenic mechanism of Brucella and provide new ideas for clinical vaccine research and development.<\/jats:p>","DOI":"10.3390\/ijms222413637","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"13637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["The VirB System Plays a Crucial Role in Brucella Intracellular Infection"],"prefix":"10.3390","volume":"22","author":[{"given":"Xue","family":"Xiong","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojing","family":"Gu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Yujinxiang Street 573, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwei","family":"Jiao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Southwest University, Chongqing 402460, China"},{"name":"National Center of Technology Innovation for Pigs, Chongqing 402460, China"},{"name":"Veterinary Scientific Engineering Research Center, Chongqing 402460, China"},{"name":"Immunology Research Center, Medical Research Institute, Southwest University, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Njeru, J., Wareth, G., Melzer, F., Henning, K., Pletz, M.W., Heller, R., and Neubauer, H. (2016). Systematic review of brucellosis in Kenya: Disease frequency in humans and animals and risk factors for human infection. BMC Public Health, 16.","DOI":"10.1186\/s12889-016-3532-9"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/tbed.13377","article-title":"Brucella microti-like prevalence in French farms producing frogs","volume":"67","author":"Jay","year":"2020","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1574-6976.2010.00211.x","article-title":"Towards a Brucella vaccine for humans","volume":"34","author":"Perkins","year":"2010","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9421","DOI":"10.1038\/s41598-020-65760-0","article-title":"Shedding of Brucella melitensis happens through milk macrophages in the murine model of infection","volume":"10","author":"Jansen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.21307\/pjm-2018-029","article-title":"Brucella\u2014Virulence Factors, Pathogenesis and Treatment","volume":"67","author":"Glowacka","year":"2018","journal-title":"Pol. J. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jprot.2019.01.008","article-title":"Lable-free based comparative proteomic analysis of secretory proteins of rough Brucella mutants","volume":"195","author":"Li","year":"2019","journal-title":"J. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mib.2012.11.005","article-title":"Brucella T4SS: The VIP pass inside host cells","volume":"16","author":"Lacerda","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_8","first-page":"72","article-title":"Type IV secretion system of Brucella spp","volume":"5","author":"Ke","year":"2015","journal-title":"and its effectors. Front. Cell. Infect. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4849","DOI":"10.1128\/JB.182.17.4849-4855.2000","article-title":"A homologue of an operon required for DNA transfer in Agrobacterium is required in Brucella abortus for virulence and intracellular multiplication","volume":"182","author":"Sieira","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1046\/j.1365-2958.1999.01569.x","article-title":"A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis","volume":"33","author":"Cazevieille","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1073\/pnas.032514299","article-title":"The Brucella suis virB operon is induced intracellularly in macrophages","volume":"99","author":"Boschiroli","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5143","DOI":"10.1128\/IAI.72.9.5143-5149.2004","article-title":"Differential requirements for VirB1 and VirB2 during Brucella abortus infection","volume":"72","author":"Sun","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6048","DOI":"10.1128\/IAI.73.9.6048-6054.2005","article-title":"Brucella abortus virB12 is expressed during infection but is not an essential component of the type IV secretion system","volume":"73","author":"Sun","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1128\/JB.00406-08","article-title":"VirB3 to VirB6 and VirB8 to VirB11, but not VirB7, are essential for mediating persistence of Brucella in the reticuloendothelial system","volume":"190","author":"Rolan","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11493","DOI":"10.1073\/pnas.172390299","article-title":"Peptide linkage mapping of the Agrobacterium tumefaciens vir-encoded type IV secretion system reveals protein subassemblies","volume":"99","author":"Ward","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","first-page":"31","article-title":"Structural and Molecular Biology of Type IV Secretion Systems","volume":"413","author":"Berge","year":"2017","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1128\/JB.182.10.2761-2770.2000","article-title":"Enzymology of type IV macromolecule secretion systems: The conjugative transfer regions of plasmids RP4 and R388 and the cag pathogenicity island of Helicobacter pylori encode structurally and functionally related nucleoside triphosphate hydrolases","volume":"182","author":"Krause","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jmb.2006.04.060","article-title":"A large domain swap in the VirB11 ATPase of Brucella suis leaves the hexameric assembly intact","volume":"360","author":"Hare","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrmicro2218","article-title":"The structural biology of type IV secretion systems","volume":"7","author":"Fronzes","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1021\/bi300298v","article-title":"Type IV secretion system core component VirB8 from Brucella binds to the globular domain of VirB5 and to a periplasmic domain of VirB6","volume":"51","author":"Sivanesan","year":"2012","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/j.febslet.2015.05.051","article-title":"VirB6 and VirB10 from the Brucella type IV secretion system interact via the N-terminal periplasmic domain of VirB6","volume":"589","author":"Mary","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4596","DOI":"10.1073\/pnas.0408927102","article-title":"Structures of two core subunits of the bacterial type IV secretion system, VirB8 from Brucella suis and ComB10 from Helicobacter pylori","volume":"102","author":"Terradot","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1111\/febs.14049","article-title":"Monomer-to-dimer transition of Brucella suis type IV secretion system component VirB8 induces conformational changes","volume":"284","author":"Sharifahmadian","year":"2017","journal-title":"FEBS J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1146\/annurev-biochem-062911-102821","article-title":"Structural Biology of Bacterial Type IV Secretion Systems","volume":"84","author":"Waksman","year":"2015","journal-title":"Annu. Rev. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1126\/science.1166101","article-title":"Structure of a type IV secretion system core complex","volume":"323","author":"Fronzes","year":"2009","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1128\/jb.179.4.1211-1218.1997","article-title":"The lipoprotein VirB7 interacts with VirB9 in the membranes of Agrobacterium tumefaciens","volume":"179","author":"Baron","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/infdis\/jiu673","article-title":"Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain","volume":"211","author":"Keriel","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1099\/mic.0.2007\/010462-0","article-title":"The VirB5 protein localizes to the T-pilus tips in Agrobacterium tumefaciens","volume":"153","author":"Aly","year":"2007","journal-title":"Microbiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105026","DOI":"10.1016\/j.actatropica.2019.05.017","article-title":"Screening and identification of a human domain antibody against Brucella abortus VirB5","volume":"197","author":"Deng","year":"2019","journal-title":"Acta Trop."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6551","DOI":"10.1128\/JB.00480-07","article-title":"VirB1* promotes T-pilus formation in the vir-Type IV secretion system of Agrobacterium tumefaciens","volume":"189","author":"Zupan","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12941-017-0182-4","article-title":"Brucella melitensis VirB12 recombinant protein is a potential marker for serodiagnosis of human brucellosis","volume":"16","author":"Mirkalantari","year":"2017","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1128\/IAI.74.1.108-117.2006","article-title":"The Brucella suis type IV secretion system assembles in the cell envelope of the heterologous host Agrobacterium tumefaciens and increases IncQ plasmid pLS1 recipient competence","volume":"74","author":"Carle","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrmicro.2017.40","article-title":"A comprehensive guide to pilus biogenesis in Gram-negative bacteria","volume":"15","author":"Hospenthal","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4483","DOI":"10.1021\/bi902201y","article-title":"Quantitative analysis of VirB8-VirB9-VirB10 interactions provides a dynamic model of type IV secretion system core complex assembly","volume":"49","author":"Sivanesan","year":"2010","journal-title":"Biochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17228","DOI":"10.1073\/pnas.0405843101","article-title":"Agrobacterium VirB10, an ATP energy sensor required for type IV secretion","volume":"101","author":"Cascales","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"26349","DOI":"10.1074\/jbc.M502347200","article-title":"Identification of the VirB4-VirB8-VirB5-VirB2 pilus assembly sequence of type IV secretion systems","volume":"280","author":"Yuan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1099\/mic.0.28326-0","article-title":"The putative lytic transglycosylase VirB1 from Brucella suis interacts with the type IV secretion system core components VirB8, VirB9 and VirB11","volume":"151","author":"Hoppner","year":"2005","journal-title":"Microbiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/j.1462-5822.2011.01601.x","article-title":"Identification of a Brucella spp. secreted effector specifically interacting with human small GTPase Rab2","volume":"13","author":"Jamet","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nkengfac, B., Pouyez, J., Bauwens, E., Vandenhaute, J., Letesson, J.J., Wouters, J., and De Bolle, X. (2012). Structural analysis of Brucella abortus RicA substitutions that do not impair interaction with human Rab2 GTPase. BMC Biochem., 13.","DOI":"10.1186\/1471-2091-13-16"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9020","DOI":"10.1021\/bi401373r","article-title":"Molecular Structure of the Brucella abortus Metalloprotein RicA, a Rab2-Binding Virulence Effector","volume":"52","author":"Herrou","year":"2013","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Taguchi, Y., Imaoka, K., Kataoka, M., Uda, A., Nakatsu, D., Horii-Okazaki, S., Kunishige, R., Kano, F., and Murata, M. (2015). Yip1A, a novel host factor for the activation of the IRE1 pathway of the unfolded protein response during Brucella infection. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004747"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhi, F.J., Zhou, D., Bai, F.R., Li, J.M., Xiang, C.X., Zhang, G.D., Jin, Y.P., and Wang, A.H. (2019). VceC Mediated IRE1 Pathway and Inhibited CHOP-induced Apoptosis to Support Brucella Replication in Goat Trophoblast Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174104"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s00284-019-01651-6","article-title":"Deletion of the Type IV Secretion System Effector VceA Promotes Autophagy and Inhibits Apoptosis in Brucella-Infected Human Trophoblast Cells","volume":"76","author":"Zhang","year":"2019","journal-title":"Curr. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1111\/j.1365-2958.2008.06487.x","article-title":"Identification of VceA and VceC, two members of the VjbR regulon that are translocated into macrophages by the Brucella type IV secretion system","volume":"70","author":"Sun","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Salcedo, S.P., Marchesini, M.I., Lelouard, H., Fugier, E., Jolly, G., Balor, S., Muller, A., Lapaque, N., Demaria, O., and Alexopoulou, L. (2008). Brucella control of dendritic cell maturation is dependent on the TIR-Containing protein btp1. PLoS Path., 4.","DOI":"10.1371\/journal.ppat.0040021"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"956","DOI":"10.4049\/jimmunol.0902008","article-title":"Subversion of Innate Immune Responses by Brucella through the Targeted Degradation of the TLR Signaling Adapter, MAL","volume":"184","author":"Sengupta","year":"2010","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1074\/jbc.M113.523274","article-title":"Mechanism of Bacterial Interference with TLR4 Signaling by Brucella Toll\/Interleukin-1 Receptor Domain-containing Protein TcpB","volume":"289","author":"Alaidarous","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fcimb.2013.00028","article-title":"BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions","volume":"3","author":"Salcedo","year":"2013","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.bbrc.2011.11.104","article-title":"The Brucella TIR-like protein TcpB interacts with the death domain of MyD88","volume":"417","author":"Chaudhary","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Coronas-Serna, J.M., Louche, A., Rodriguez-Escudero, M., Roussin, M., Imbert, P.R.C., Rodriguez-Escudero, I., Terradot, L., Molina, M., Gorvel, J.P., and Cid, V.J. (2020). The TIR-domain containing effectors BtpA and BtpB from Brucella abortus impact NAD metabolism. PLoS Path., 16.","DOI":"10.1371\/journal.ppat.1007979"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Myeni, S., Child, R., Ng, T.W., Kupko, J.J., Wehrly, T.D., Porcella, S.F., Knodler, L.A., and Celli, J. (2013). Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins. PLoS Path., 9.","DOI":"10.1371\/journal.ppat.1003556"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3389\/fcimb.2016.00153","article-title":"A T4SS Effector Targets Host Cell Alpha-Enolase Contributing to Brucella abortus Intracellular Lifestyle","volume":"6","author":"Marchesini","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/cmi.12224","article-title":"Identification of a type IV secretion substrate of Brucella abortus that participates in the early stages of intracellular survival","volume":"16","author":"Dohmer","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Celli, J. (2019). The Intracellular Life Cycle of Brucella spp. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.BAI-0006-2019"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1600-0854.2008.00718.x","article-title":"Brucella intracellular replication requires trafficking through the late endosomal\/lysosomal compartment","volume":"9","author":"Starr","year":"2008","journal-title":"Traffic"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1574-6976.2012.00334.x","article-title":"Internal affairs: Investigating the Brucella intracellular lifestyle","volume":"36","author":"Gorvel","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1073\/pnas.0406873102","article-title":"Brucella coopts the small GTPase Sar1 for intracellular replication","volume":"102","author":"Celli","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.chom.2011.12.002","article-title":"Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle","volume":"11","author":"Starr","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1128\/IAI.68.7.4102-4107.2000","article-title":"Identification of genes required for chronic persistence of Brucella abortus in mice","volume":"68","author":"Hong","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5711","DOI":"10.1128\/IAI.66.12.5711-5724.1998","article-title":"Brucella abortus transits through the autophagic pathway and replicates in the endoplasmic reticulum of nonprofessional phagocytes","volume":"66","author":"Meresse","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1462-5822.2001.00102.x","article-title":"Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole","volume":"3","author":"Comerci","year":"2001","journal-title":"Cell. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1084\/jem.20030088","article-title":"Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum","volume":"198","author":"Celli","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/S0092-8674(00)80379-7","article-title":"Visualization of ER-to-Golgi transport in living cells reveals a sequential mode of action for COPII and COPI","volume":"90","author":"Scales","year":"1997","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0955-0674(02)00348-4","article-title":"COPII-dependent transport from the endoplasmic reticulum","volume":"14","author":"Barlowe","year":"2002","journal-title":"Curr. Opin. Cell. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1128\/JB.01124-09","article-title":"Metabolic Control of Virulence Genes in Brucella abortus: HutC Coordinates virB Expression and the Histidine Utilization Pathway by Direct Binding to Both Promoters","volume":"192","author":"Sieira","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fugier, E., Salcedo, S.P., de Chastellier, C., Pophillat, M., Muller, A., Arce-Gorvel, V., Fourquet, P., and Gorvel, J.P. (2009). The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication. PLoS Path., 5.","DOI":"10.1371\/journal.ppat.1000487"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e00418-12","DOI":"10.1128\/mBio.00418-12","article-title":"Sensing of bacterial type IV secretion via the unfolded protein response","volume":"4","author":"Starr","year":"2013","journal-title":"mBio"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature17631","article-title":"NOD1\/NOD2 signaling links ER stress with inflammation","volume":"532","author":"Byndloss","year":"2016","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/IAI.01227-15","article-title":"The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor beta 1 in Hepatic Stellate Cells","volume":"84","author":"Benitez","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8561","DOI":"10.1073\/pnas.0503363102","article-title":"Gene expression patterns define key transcriptional events in cell-cycle regulation by cAMP and protein kinase A","volume":"102","author":"Zambon","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e03350-19","DOI":"10.1128\/mBio.03350-19","article-title":"Epistatic Interplay between Type IV Secretion Effectors Engages the Small GTPase Rab2 in the Brucella Intracellular Cycle","volume":"11","author":"Smith","year":"2020","journal-title":"mBio"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.chom.2017.07.017","article-title":"A Brucella Type IV Effector Targets the COG Tethering Complex to Remodel Host Secretory Traffic and Promote Intracellular Replication","volume":"22","author":"Miller","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fcimb.2016.00019","article-title":"Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro","volume":"6","author":"Wang","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3389\/fcimb.2018.00103","article-title":"Activation of Host IRE1alpha-Dependent Signaling Axis Contributes the Intracellular Parasitism of Brucella melitensis","volume":"8","author":"Pandey","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"54046","DOI":"10.1074\/jbc.M409472200","article-title":"Glyceraldehyde-3-phosphate dehydrogenase interacts with Rab2 and plays an essential role in endoplasmic reticulum to Golgi transport exclusive of its glycolytic activity","volume":"279","author":"Tisdale","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Smith, E.P., Miller, C.N., Child, R., Cundiff, J.A., and Celli, J. (2016). Postreplication Roles of the Brucella VirB Type IV Secretion System Uncovered via Conditional Expression of the VirB11 ATPase. mBio, 7.","DOI":"10.1128\/mBio.01730-16"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/j.1365-2958.2004.04316.x","article-title":"Integration host factor is involved in transcriptional regulation of the Brucella abortus virB operon","volume":"54","author":"Sieira","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.tim.2009.05.006","article-title":"Brucella regulators: Self-control in a hostile environment","volume":"17","author":"Petersen","year":"2009","journal-title":"Trends Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1093\/nar\/gkx165","article-title":"ChIP-seq analysis of the LuxR-type regulator VjbR reveals novel insights into the Brucella virulence gene expression network","volume":"45","author":"Kleinman","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fcimb.2017.00422","article-title":"Brucella Rough Mutant Induce Macrophage Death via Activating IRE1alpha Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion","volume":"7","author":"Li","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s12275-014-3570-x","article-title":"A functional and phylogenetic comparison of quorum sensing related genes in Brucella melitensis 16M","volume":"52","year":"2014","journal-title":"J. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1016\/j.ijbiomac.2020.08.134","article-title":"The UTP-glucose-1-phosphate uridylyltransferase of Brucella melitensis inhibits the activation of NF-kappaB via regulating the bacterial type IV secretion system","volume":"164","author":"Zhou","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1128\/JB.05623-11","article-title":"The RNA Chaperone Hfq Independently Coordinates Expression of the VirB Type IV Secretion System and the LuxR-Type Regulator BabR in Brucella abortus 2308","volume":"194","author":"Caswell","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_84","first-page":"1570","article-title":"Deletion of the Small RNA Chaperone Protein Hfq down Regulates Genes Related to Virulence and Confers Protection against Wild-Type Brucella Challenge in Mice","volume":"6","author":"Lei","year":"2015","journal-title":"Front. Microbiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13637\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:34Z","timestamp":1760168974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":84,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413637"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413637","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}