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In this study, we utilized transcriptome sequencing to compare the transcriptional profiles of\n            <jats:italic>Photobacterium damselae<\/jats:italic>\n            subsp.\n            <jats:italic>damselae<\/jats:italic>\n            , a generalist pathogen that causes disease in diverse marine animals and fatal infections in humans at NaCl concentrations that mimic the free-living lifestyle or host internal milieu, respectively. We here show that NaCl concentration constitutes a major regulatory signal that shapes the transcriptome and uncover 1,808 differentially expressed genes (888 upregulated and 920 downregulated in response to low-salt conditions). Growth at 3% NaCl, a salinity that mimics the free-living lifestyle, upregulated genes involved in energy production, nitrogen metabolism, transport of compatible solutes, utilization of trehalose and fructose, and carbohydrate and amino acid metabolism with strong upregulation of the arginine deiminase system (ADS). In addition, we observed a marked increase in resistance to antibiotics at 3% NaCl. On the contrary, the low salinity conditions (1% NaCl) that mimic those encountered in the host triggered a virulence gene expression profile that maximized the production of the type 2 secretion system (T2SS)-dependent cytotoxins damselysin, phobalysin P, and a putative PirAB-like toxin, observations that were corroborated by the analysis of the secretome. Low salinity also upregulated the expression of iron-acquisition systems, efflux pumps, and other functions related to stress response and virulence. The results of this study greatly expand our knowledge of the salinity-responsive adaptations of a generalist and versatile marine pathogen.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Pathogenic\n              <jats:italic>Vibrionaceae<\/jats:italic>\n              species experience continuous shifts of NaCl concentration in their life cycles. However, the impact of salinity changes in gene regulation has been studied in a small number of\n              <jats:italic>Vibrio<\/jats:italic>\n              species. In this study, we analyzed the transcriptional response of\n              <jats:italic>Photobacterium damselae<\/jats:italic>\n              subsp.\n              <jats:italic>damselae<\/jats:italic>\n              (\n              <jats:italic>Pdd<\/jats:italic>\n              ), a generalist and facultative pathogen, to changes in salinity, and demonstrate that growth at 1% NaCl in comparison to 3% NaCl triggers a virulence program of gene expression, with a major impact in the T2SS-dependent secretome. The decrease in NaCl concentration encountered by bacteria on entry into a host is proposed to constitute a regulatory signal that upregulates a genetic program involved in host invasion and tissue damage, nutrient scavenging (notably iron), and stress responses. This study will surely inspire new research on\n              <jats:italic>Pdd<\/jats:italic>\n              pathobiology, as well as on other important pathogens of the family\n              <jats:italic>Vibrionaceae<\/jats:italic>\n              and related taxa whose salinity regulons still await investigation.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msystems.01253-22","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T13:00:28Z","timestamp":1686229228000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Low salinity activates a virulence program in the generalist marine pathogen\n            <i>Photobacterium damselae<\/i>\n            subsp.\n            <i>damselae<\/i>"],"prefix":"10.1128","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-0648","authenticated-orcid":true,"given":"Alba V.","family":"Barca","sequence":"first","affiliation":[{"name":"Departamento de Microbiolox\u00eda e Parasitolox\u00eda, Instituto de Acuicultura, Universidade de Santiago de Compostela , Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4229-3134","authenticated-orcid":true,"given":"Ana","family":"Vences","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolox\u00eda e Parasitolox\u00eda, Instituto de Acuicultura, Universidade de Santiago de Compostela , Santiago de Compostela, Spain"}]},{"given":"Mateus S.","family":"Terceti","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolox\u00eda e Parasitolox\u00eda, Instituto de Acuicultura, Universidade de Santiago de Compostela , Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4044-6328","authenticated-orcid":true,"given":"Ana","family":"do Vale","sequence":"additional","affiliation":[{"name":"Fish Immunology and Vaccinology Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto, Portugal"},{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-4064","authenticated-orcid":true,"given":"Carlos R.","family":"Osorio","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolox\u00eda e Parasitolox\u00eda, Instituto de Acuicultura, Universidade de Santiago de Compostela , Santiago de Compostela, Spain"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.05.009"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.68.3.403-431.2004"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0010-y"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10393-007-0134-0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00038"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01540-08"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2012.02805.x"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijfoodmicro.2009.11.006"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/jfd.13520"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-017-1030-6"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/foods11060840"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8040555"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114376"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0723-2020(89)80080-3"},{"key":"e_1_3_4_16_2","first-page":"437","article-title":"Aislamiento de vibrios enteropat\u00f3genos de bivalvos y cieno del golfo de Nicoya, Costa Rica","volume":"38","author":"Cort\u00e9s G","year":"1990","unstructured":"Cort\u00e9s G , Antill\u00f3n F . 1990. 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