{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:30:57Z","timestamp":1772245857683,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971907"],"award-info":[{"award-number":["81971907"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970135"],"award-info":[{"award-number":["31970135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n                    is a zoonotic pathogen that usually affects patients' lungs and causes serious melioidosis. The interaction of\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    with its hosts is complex, and cellular response to\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    infection in humans still remains to be elucidated. In this study, transcriptomic profiling of\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    -infected human lung epithelial A549 cells was performed to characterize the cellular response dynamics during the early infection (EI) stage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the online databases DAVID 6.8 and KOBAS 3.0. Real-time quantitative PCR and western blot were used for validation experiments. Compared with the negative control group (NC), a set of 36 common genes varied over time with a cut-off level of 1.5-fold change, and a\n                    <jats:italic>P<\/jats:italic>\n                    -value &amp;lt; 0.05 was identified. Bioinformatics analysis indicated that the PERK-mediated unfolded protein response (UPR) was enriched as the most noteworthy biological process category, which was enriched as a branch of UPR in the signaling pathway of protein processing in the endoplasmic reticulum. Other categories, such as inflammatory responses, cell migration, and apoptosis, were also focused. The molecular chaperone Bip (GRP78), PERK, and PERK sensor-dependent phosphorylation of eIF2\u03b1 (p-eIF2\u03b1) and ATF4 were verified to be increasing over time during the EI stage, suggesting that\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    infection activated the PERK-mediated UPR in A549 cells. Collectively, these results provide important initial insights into the intimate interaction between\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    and lung epithelial cells, which can be further explored toward the elucidation of the cellular mechanisms of\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    infections in humans.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2020.585203","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T02:32:01Z","timestamp":1607394721000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptome Analysis Reveals Unfolded Protein Response Was Induced During the Early Stage of Burkholderia pseudomallei Infection in A549 Cells"],"prefix":"10.3389","volume":"11","author":[{"given":"Chenglong","family":"Rao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yupei","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meijuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingmin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolian","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhu","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3389\/fmicb.2011.00170","article-title":"Strategies for intracellular survival of Burkholderia pseudomallei","volume":"2","author":"Allwood","year":"2011","journal-title":"Front Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.ygeno.2019.04.002","article-title":"Transcriptome analysis of Burkholderia pseudomallei SCV reveals an association with virulence, stress resistance and intracellular persistence","volume":"112","author":"Al-Maleki","year":"2020","journal-title":"Genomics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s12920-019-0575-7","article-title":"Transcriptome analysis of human monocytic cells infected with Burkholderia species and exploration of pentraxin-3 as part of the innate immune response against the organisms","volume":"12","author":"Aschenbroich","year":"2019","journal-title":"BMC Med Genomics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1003986","DOI":"10.1371\/journal.ppat.1003986","article-title":"Caspase-1-dependent and -independent cell death pathways in Burkholderia pseudomallei infection of macrophages","volume":"10","author":"Bast","year":"2014","journal-title":"PLoS Pathog"},{"key":"B5","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/35014014","article-title":"Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response","volume":"2","author":"Bertolotti","year":"2000","journal-title":"Nat. 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