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This review provides an integrated overview of key virulence mechanisms employed by\n                    <jats:italic>Brucella<\/jats:italic>\n                    , with emphasis on the VirB Type IV secretion system (T4SS), cyclic \u03b2\u22121,2\u2010glucans (C\u03b2G), lipopolysaccharide (LPS) and the bacterium's intracellular replication cycle. These factors enable the pathogen to evade host immune recognition, remodel intracellular compartments, and maintain long\u2010term survival in diverse tissues. Building on recent advances, we propose a functional hierarchy of VirB T4SS effectors that distinguishes core components required for intracellular persistence from context\u2010dependent effectors that modulate tissue specificity and disease severity. By linking VirB T4SS activity with C\u03b2G\u2010driven alterations of phagosomal trafficking and LPS\u2010mediated dampening of Toll\u2010like receptor 4 signaling, we outline a multilayered model of immune escape and chronic infection. On this basis, we identify non\u2010redundant T4SS effectors, C\u03b2G biosynthetic enzymes and defined LPS modifications as priority candidates for the development of targeted diagnostics, host\u2010directed or anti\u2010virulence therapies, and next\u2010generation vaccines against brucellosis.\n                  <\/jats:p>","DOI":"10.1002\/jobm.70167","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:27:27Z","timestamp":1774934847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Brucella<\/i>\n                    spp. \u2013 Emerging Insights Into Virulence Strategies: T4SS, C\u03b2G, Intracellular Replication, and Beyond"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6882-9862","authenticated-orcid":false,"given":"Kokila","family":"Manickam","sequence":"first","affiliation":[{"name":"Central Research Laboratory for Biomedical Research, Vinayaka Mission's Medical College and Hospital Vinayaka Mission's Research Foundation (Deemed to be University) Puducherry India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-7405","authenticated-orcid":false,"given":"Suganya","family":"Kannan","sequence":"additional","affiliation":[{"name":"Central Research Laboratory for Biomedical Research, Vinayaka Mission's Medical College and Hospital Vinayaka Mission's Research Foundation (Deemed to be University) Puducherry India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050570"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.BAI-0016-2019"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00722.x"},{"key":"e_1_2_15_5_1","first-page":"97","volume-title":"Brucella: Molecular Microbiology and Genomics","author":"O'Callaghan D.","year":"2012"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03350-19"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413637"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112581"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2009.07.001"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1189543"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.13479"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.102965"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.13344"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.46234\/ccdcw2025.020"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2909.230052"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-45-76"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsml\/uqaf036"},{"key":"e_1_2_15_18_1","unstructured":"World Health Organization.Brucellosis. 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