Transferrin knockout reveals a tolerance phenotype against Piscirickettsia salmonis in Atlantic salmon phagocytes

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dc.catalogadorjca
dc.contributor.authorMejías, Madelaine
dc.contributor.authorSáez Beltrán, Alejandro José
dc.contributor.authorEscorza Sius, Amanda Paz
dc.contributor.authorGaldames Contreras, Felipe
dc.contributor.authorJin, Yehwa
dc.contributor.authorDettleff Faundes, Phillip Jame
dc.contributor.authorOjeda, Ingrid
dc.contributor.authorPulgar, Rodrigo
dc.contributor.authorEscobar Aguirre, Sebastián
dc.date.accessioned2025-10-01T18:56:55Z
dc.date.available2025-10-01T18:56:55Z
dc.date.issued2025
dc.description.abstractSalmonid rickettsial septicemia (SRS), caused by Piscirickettsia salmonis, is a major challenge in Chilean aquaculture. We evaluated the impact of the vaccine on fish survival, bacterial load, and iron metabolism-related gene expression under field conditions. Atlantic salmon received either a pentavalent inactivated vaccine plus a live attenuated P. salmonis vaccine (SIA) or a tetravalent control vaccine (SS). While survival was similar early (≤ 28 weeks post-seawater transfer), SIA-vaccinated fish showed greater survival by week 41 (85% vs. 52%). Quantitative PCR confirmed a reduced bacterial load in the SIA group during active infection. Expression analysis revealed distinct temporal regulation of iron metabolism genes: ferritin and hepcidin were upregulated in freshwater, whereas transferrin and its receptor were elevated in seawater in the SIA group, suggesting a link between iron homeostasis and vaccine-induced protection. To further investigate the role of transferrin, we generated transferrin-knockout (TF-KO) phagocytes using CRISPR/Cas9. In vitro infection assays revealed that, compared with wild-type (TF-WT) cells, TF-KO cells presented reduced cytopathic effects, decreased formation of P. salmonis-containing vacuoles (PCVs), and improved viability. Surprisingly, no differences in bacterial load or iron-related gene expression were detected between TF-KO and TF-WT cells, indicating that transferrin disruption did not directly alter iron homeostasis. Global transcriptomic analysis revealed 311 differentially expressed genes in TF-KO cells, with functional enrichment in metal-binding and zinc-dependent processes but no direct association with iron metabolism. These findings suggest that transferrin deficiency confers an infection-tolerant phenotype through transcriptional reprogramming unrelated to iron regulation, highlighting novel mechanisms of host‒pathogen interactions and potential avenues for SRS control in aquaculture.
dc.fechaingreso.objetodigital2025-09-30
dc.format.extent12 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1186/s13567-025-01607-8
dc.identifier.issn1297-9716
dc.identifier.urihttps://doi.org/10.1186/s13567-025-01607-8
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/105860
dc.information.autorucFacultad de Agronomía e Ingenieria Forestal;Sáez Beltrán, Alejandro José;S/I;1027712
dc.information.autorucFacultad de Ciencias Biológicas;Escorza Sius, Amanda Paz;0009-0003-2253-1515;221074
dc.information.autorucEscuela de Medicina Veterinaria;Dettleff Faundes, Phillip James;S/I;1252622
dc.information.autorucFacultad de Agronomía e Ingenieria Forestal; Escobar Aguirre, Sebastián Gonzalo; 0000-0001-8826-2096; 1092624
dc.issue.numero180
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final12
dc.pagina.inicio1
dc.revistaVeterinary Research
dc.rightsacceso abierto
dc.rights.licenseCreative Commons Attribution 4.0 International License
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectVaccines
dc.subjectSalmo salar
dc.subjectTransferrin
dc.subjectGene editing
dc.subjectPiscirickettsia salmonis
dc.subjectSRS
dc.subject.ddc570
dc.subject.deweyBiologíaes_ES
dc.subject.ods14 Life below water
dc.subject.ods03 Good health and well-being
dc.subject.odspa14 Vida submarina
dc.subject.odspa03 Salud y bienestar
dc.titleTransferrin knockout reveals a tolerance phenotype against Piscirickettsia salmonis in Atlantic salmon phagocytes
dc.typeartículo
dc.volumen56
sipa.codpersvinculados1027712
sipa.codpersvinculados221074
sipa.codpersvinculados1252622
sipa.codpersvinculados1092624
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