{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T10:55:12Z","timestamp":1784804112369,"version":"3.55.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"crossref","award":["AP20VSD&B000C087"],"award-info":[{"award-number":["AP20VSD&B000C087"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI12660101"],"award-info":[{"award-number":["AI12660101"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Texas Medical Branch","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2023,10,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n            (\n            <jats:italic>Bpm<\/jats:italic>\n            ) is the causative agent of melioidosis disease.\n            <jats:italic>Bpm<\/jats:italic>\n            is a facultative intracellular pathogen with a complex life cycle inside host cells. Pathogenic success depends on a variety of virulence factors with one of the most critical being the type 6 secretion system (T6SS).\n            <jats:italic>Bpm<\/jats:italic>\n            uses the T6SS to move into neighboring cells, resulting in multinucleated giant cell (MNGC) formation, a strategy used to disseminate from cell to cell. Our prior study using a dual RNA-seq analysis to dissect T6SS-mediated virulence on intestinal epithelial cells identified BicA as a factor upregulated in a T6SS mutant. BicA regulates both type 3 secretion system (T3SS) and T6SSs; however, the extent of its involvement during disease progression is unclear. To fully dissect the role of BicA during systemic infection, we used two macrophage cell lines paired with a pulmonary\n            <jats:italic>in vivo<\/jats:italic>\n            challenge murine model. We found that \u0394\n            <jats:italic>bicA<\/jats:italic>\n            has a distinct intracellular replication defect in both immortalized and primary macrophages, which begins as early as 1 h post-infection. This intracellular defect is linked with the lack of cell-to-cell dissemination and MNGC formation as well as a defect in T3SS expression. The\n            <jats:italic>in vitro<\/jats:italic>\n            phenotype translated\n            <jats:italic>in vivo<\/jats:italic>\n            as \u0394\n            <jats:italic>bicA<\/jats:italic>\n            was attenuated in a pulmonary model of infection, demonstrating a distinct macrophage activation profile and a lack of pathological features present in the wild type. Overall, these results highlight the role of BicA in regulating intracellular virulence and demonstrate that specific regulation of secretion systems has a significant effect on host response and\n            <jats:italic>Bpm<\/jats:italic>\n            pathogenesis.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Melioidosis is an understudied tropical disease that still results in ~50% fatalities in infected patients. It is caused by the Gram-negative bacillus\n              <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n              (\n              <jats:italic>Bpm<\/jats:italic>\n              ).\n              <jats:italic>Bpm<\/jats:italic>\n              is an intracellular pathogen that disseminates from the infected cell to target organs, causing disseminated disease. The regulation of secretion systems involved in entry and cell-to-cell spread is poorly understood. In this work, we characterize the role of BicA as a regulator of secretion systems during infection of macrophages\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              . Understanding how these virulence factors are controlled will help us determine their influence on the host cells and define the macrophage responses associated with bacterial clearance.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00378-23","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T13:07:16Z","timestamp":1695906436000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["<i>Burkholderia pseudomallei<\/i>\n            BicA protein promotes pathogenicity in macrophages by regulating invasion, intracellular survival, and virulence"],"prefix":"10.1128","volume":"8","author":[{"given":"Jacob L.","family":"Stockton","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Texas Medical Branch , Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nittaya","family":"Khakhum","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Texas Medical Branch , Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather L.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6450-0643","authenticated-orcid":false,"given":"Alfredo G.","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Texas Medical Branch , Galveston, Texas, USA"},{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.107"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2015.8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2712.211756"},{"key":"e_1_3_4_5_2","unstructured":"CDC\n. 2021. CDC discovers rare bacteria in aromatherapy product. Available from: https:\/\/www.cdc.gov\/media\/releases\/2021\/p1022-aromatherapy-bacteria.html"},{"key":"e_1_3_4_6_2","unstructured":"MSDH\n. 2022. Rare bacteria discovered on Mississippi Gulf Coast: Burkholderia Pseudomallei. Available from: https:\/\/msdh.ms.gov\/msdhsite\/index.cfm\/23 24573 341 html#:~:text=Burkholderia%20pseudomallei%20normally%20occurs%20in%20tropical%20and%20sub-tropical on%20the%20Gulf%20Coast%20should%20take%20recommended%20precautions.%22"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2606.190975"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2020.1791089"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftw070"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73887-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01218-10"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.000789"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03339"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00654-20"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2111950"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05148-11"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-014-0206-6"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.620510"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.3.782-790.1996"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31778-8"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftaa009"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2018.09.028"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-020-0333-9"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0086MA"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00394-7"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3855\/jidc.12051"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.002"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710433114"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.8.2262-2268.2000"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13602"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07124.x"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00263-08"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00078"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.585285"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.10.014"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00570-18"}],"container-title":["mSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00378-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00378-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T16:35:37Z","timestamp":1698165337000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msphere.00378-23"}},"subtitle":[],"editor":[{"given":"Sarah E. F.","family":"D'Orazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10,24]]}},"alternative-id":["10.1128\/msphere.00378-23"],"URL":"https:\/\/doi.org\/10.1128\/msphere.00378-23","relation":{},"ISSN":["2379-5042"],"issn-type":[{"value":"2379-5042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]},"assertion":[{"value":"2023-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00378-23"}}