{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:08:21Z","timestamp":1779426501561,"version":"3.53.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    Columnaris disease, caused by\n                    <jats:italic>Flavobacterium columnare<\/jats:italic>\n                    , represents one of the most economically devastating bacterial infections in global freshwater aquaculture. Despite its significant impact, the molecular mechanisms underlying\n                    <jats:italic>F. columnare<\/jats:italic>\n                    pathogenesis remain largely unexplored. Signal peptide peptidase A (SppA) plays a crucial role in bacterial protein secretion by degrading residual signal peptides after protein translocation, yet its function in\n                    <jats:italic>F. columnare<\/jats:italic>\n                    physiology and virulence has not been characterized. Here, we employed a targeted in-frame gene knockout approach to investigate the role of\n                    <jats:italic>sppA<\/jats:italic>\n                    in\n                    <jats:italic>F. columnare<\/jats:italic>\n                    . The \u0394\n                    <jats:italic>sppA<\/jats:italic>\n                    mutant exhibited pleiotropic phenotypes including increased outer membrane vesicle (OMV) production (3.8-fold higher compared to the wild type), loss of gliding motility, enhanced efflux pump activity at the transcriptomic level, and reduced virulence. Transcriptomic profiling of the \u0394\n                    <jats:italic>sppA<\/jats:italic>\n                    mutant revealed significant upregulation of genes involved in membrane stress response, including the genes in the MacAB-TolC efflux system,\n                    <jats:italic>algU<\/jats:italic>\n                    , and\n                    <jats:italic>osmC<\/jats:italic>\n                    , compared to the wild-type state. Importantly, survival assays demonstrated its virulence was significantly attenuated in freshwater Medaka (\n                    <jats:italic>Oryzias latipes<\/jats:italic>\n                    ), with a 20% higher survival rate of fish compared to the wild type. Our findings reveal that SppA is essential for maintaining membrane homeostasis and normal cellular physiology in\n                    <jats:italic>F. columnare<\/jats:italic>\n                    and serves as one of the virulence factors during columnaris infection. These results provide important insights into the biological function of the\n                    <jats:italic>sppA<\/jats:italic>\n                    gene in\n                    <jats:italic>F. columnare<\/jats:italic>\n                    and highlight its role in bacterial protein secretion, membrane homeostasis, and pathogenesis.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2026.1784124","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:33:08Z","timestamp":1779424388000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pleiotropic effects of signal peptide peptidase A (sppA) gene deletion on membrane homeostasis, gliding motility, and virulence in Flavobacterium columnare"],"prefix":"10.3389","volume":"13","author":[{"given":"Ruoxi","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Infectious Disease and Public Health, Jockey Club College of Veterinary Medicine and Life Science, City University of Hong Kong","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Public Health, Jockey Club College of Veterinary Medicine and Life Science, City University of Hong Kong","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Xun","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University","place":["Suzhou, Jiangsu, China"]},{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiaotong-Liverpool University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shucheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Public Health, Jockey Club College of Veterinary Medicine and Life Science, City University of Hong Kong","place":["Hong Kong, Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","DOI":"10.5962\/bhl.title.49773","volume-title":"A new bacterial disease of fresh-water fishes","author":"Davis","year":"1922"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1297-9716-44-27","article-title":"Columnaris disease in fish: a review with emphasis on bacterium-host interactions","volume":"44","author":"Declercq","year":"2013","journal-title":"Vet Res"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1577\/1548-8667(2002)014<0263:TEOBDI>2.0.CO;2","article-title":"The epidemiology of bacterial diseases in food-size channel catfish","volume":"14","author":"Wagner","year":"2002","journal-title":"J Aquat Anim Health"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/BF00588387","article-title":"Columnaris infection 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