Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection
Abstract Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develo...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-10-01
|
| Series: | Veterinary Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13567-020-00845-2 |
| _version_ | 1818978383101427712 |
|---|---|
| author | Mario Caruffo Dinka Mandakovic Madelaine Mejías Ignacio Chávez-Báez Pablo Salgado Daniela Ortiz Liliana Montt Javiera Pérez-Valenzuela Francisca Vera-Tamargo José Manuel Yánez Jurij Wacyk Rodrigo Pulgar |
| author_facet | Mario Caruffo Dinka Mandakovic Madelaine Mejías Ignacio Chávez-Báez Pablo Salgado Daniela Ortiz Liliana Montt Javiera Pérez-Valenzuela Francisca Vera-Tamargo José Manuel Yánez Jurij Wacyk Rodrigo Pulgar |
| author_sort | Mario Caruffo |
| collection | DOAJ |
| description | Abstract Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens. |
| first_indexed | 2024-12-20T16:42:46Z |
| format | Article |
| id | doaj.art-5b2be8ec1d0a4e13a77c8e22082719d7 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-12-20T16:42:46Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-5b2be8ec1d0a4e13a77c8e22082719d72022-12-21T19:33:00ZengBMCVeterinary Research1297-97162020-10-0151111210.1186/s13567-020-00845-2Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infectionMario Caruffo0Dinka Mandakovic1Madelaine Mejías2Ignacio Chávez-Báez3Pablo Salgado4Daniela Ortiz5Liliana Montt6Javiera Pérez-Valenzuela7Francisca Vera-Tamargo8José Manuel Yánez9Jurij Wacyk10Rodrigo Pulgar11Escuela de Biotecnología, Facultad de Ciencias, Universidad Santo TomásLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileCenter for Research and Innovation in Aquaculture (CRIA), Universidad de ChileCenter for Research and Innovation in Aquaculture (CRIA), Universidad de ChileLaboratorio de Genómica y Genética de Interacciones Biológicas (LG2IB), Instituto de Nutrición y Tecnología de los Alimento, Universidad de ChileAbstract Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.http://link.springer.com/article/10.1186/s13567-020-00845-2Piscirickettsia salmonishost-directed therapy (HDT)iron-chelatordeferiprone (DFP)infection |
| spellingShingle | Mario Caruffo Dinka Mandakovic Madelaine Mejías Ignacio Chávez-Báez Pablo Salgado Daniela Ortiz Liliana Montt Javiera Pérez-Valenzuela Francisca Vera-Tamargo José Manuel Yánez Jurij Wacyk Rodrigo Pulgar Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection Veterinary Research Piscirickettsia salmonis host-directed therapy (HDT) iron-chelator deferiprone (DFP) infection |
| title | Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection |
| title_full | Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection |
| title_fullStr | Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection |
| title_full_unstemmed | Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection |
| title_short | Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection |
| title_sort | pharmacological iron chelation as an assisted nutritional immunity strategy against piscirickettsia salmonis infection |
| topic | Piscirickettsia salmonis host-directed therapy (HDT) iron-chelator deferiprone (DFP) infection |
| url | http://link.springer.com/article/10.1186/s13567-020-00845-2 |
| work_keys_str_mv | AT mariocaruffo pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT dinkamandakovic pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT madelainemejias pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT ignaciochavezbaez pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT pablosalgado pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT danielaortiz pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT lilianamontt pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT javieraperezvalenzuela pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT franciscaveratamargo pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT josemanuelyanez pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT jurijwacyk pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection AT rodrigopulgar pharmacologicalironchelationasanassistednutritionalimmunitystrategyagainstpiscirickettsiasalmonisinfection |