{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:08:34Z","timestamp":1784174914553,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Environtech, Dublin, Ireland"},{"name":"University of Life Sciences King Mihai I of Romania from Timisoara, Romania"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ever-growing global demand for animal protein forces the aquaculture industry to expand at a pace which imposes significant challenges in maintaining sustainable practices. This study aimed to investigate the efficacy of an organic acid mixture (Aq) in mitigating Lactococcus garvieae (L. garvieae) virulence through its effects on bacterial virulence (EPS production, biofilm, and haemolytic factors) and host pathogenicity, including its adherence to CHSE-214 cells, haemolysis, and proinflammatory responses. Our findings reveal that Aq significantly inhibits L. garvieae growth at a 0.125% concentration, suppresses EPS-related gene expression, reduces biofilm formation, and reduces cytotoxicity in fish epithelial cells (CHSE-214). Moreover, Aq decreased haemolysing gene expression (hly1, hly2 and hly3) and attenuated red blood cell haemolysis, a hallmark of L. garvieae pathogenicity. Lastly, Aq was demonstrated to induce modulation in the host immune responses, lowering IL-1\u03b2 and IL-8 expression, which are critical mediators of inflammation and pathogen recruitment. Therefore, we conclude that the main mechanism of action of Aq involves inhibiting L. garvieae adhesion to epithelial cells, reducing EPS production, and downregulating key virulence-associated genes (e.g., hly1, hly2, and hly3). After preventing L. garvieae adherence and suppressing proinflammatory cytokine expression (IL-1\u03b2 and IL-8), Aq disrupts the pathogen\u2019s ability to breach epithelial barriers and induce red blood cell lysis, thereby mitigating its virulence and pathogenicity. Our results emphasised the potential of Aq as an alternative non-antibiotic intervention for controlling piscine lactococcosis, advancing our understanding of L. garvieae pathogenesis and providing the foundation for the future integration of environmentally friendly antimicrobials into aquaculture disease management.<\/jats:p>","DOI":"10.3390\/ijms26073423","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T11:24:39Z","timestamp":1744025079000},"page":"3423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A New Strategy to Prevent Emerging Lactococcus garvieae Infections by Using Organic Acids as Antimicrobials In Vitro and Ex Vivo"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-2623","authenticated-orcid":false,"given":"Igori","family":"Balta","sequence":"first","affiliation":[{"name":"Faculty of Bioengineering of Animal Resources, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin Dan","family":"Simiz","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0153-9388","authenticated-orcid":false,"given":"Ducu","family":"Stef","sequence":"additional","affiliation":[{"name":"Faculty of Food Engineering, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-5009","authenticated-orcid":false,"given":"Ioan","family":"Pet","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering of Animal Resources, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-6631","authenticated-orcid":false,"given":"Gabi","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering of Animal Resources, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiberiu","family":"Iancu","sequence":"additional","affiliation":[{"name":"Faculty of Management and Rural Development, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-6990","authenticated-orcid":false,"given":"Iuliana","family":"Cretescu","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-3108","authenticated-orcid":false,"given":"Nicolae","family":"Corcionivoschi","sequence":"additional","affiliation":[{"name":"Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast BT4 3SD, Northern Ireland, UK"},{"name":"Academy of Romanian Scientists, 050044 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-4223","authenticated-orcid":false,"given":"Lavinia","family":"Stef","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering of Animal Resources, University of Life Sciences King Mihai I of Romania from Timisoara, 300645 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0234923","DOI":"10.1128\/aem.02349-23","article-title":"Redefining piscine lactococcosis","volume":"90","author":"Heckman","year":"2024","journal-title":"Appl. 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