title: Transcriptional response of Atlantic salmon families to Piscirickettsia salmonis infection highlights the relevance of the iron-deprivation defence system.
abstract: BACKGROUND
  Piscirickettsiosis or Salmonid Rickettsial Septicaemia (SRS) is a bacterial disease that has a major economic impact on the Chilean salmon farming industry. Despite the fact that Piscirickettsia salmonis has been recognized as a major fish pathogen for over 20 years, the molecular strategies underlying the fish response to infection and the bacterial mechanisms of pathogenesis are poorly understood. We analysed and compared the head kidney transcriptional response of Atlantic salmon (Salmo salar) families with different levels of susceptibility to P. salmonis infection in order to reveal mechanisms that might confer infection resistance.
  
  
  RESULTS
  We ranked forty full-sibling Atlantic salmon families according to accumulated mortality after a challenge with P. salmonis and selected the families with the lowest and highest cumulative mortalities for microarray gene expression analysis. A comparison of the response to P. salmonis infection between low and high susceptibility groups identified biological processes presumably involved in natural resistance to the pathogen. In particular, expression changes of genes linked to cellular iron depletion, as well as low iron content and bacterial load in the head kidney of fish from low susceptibility families, suggest that iron-deprivation is an innate immunity defence mechanism against P. salmonis. To complement these results, we predicted a set of iron acquisition genes from the P. salmonis genome. Identification of putative Fur boxes and expression of the genes under iron-depleted conditions revealed that most of these genes form part of the Fur regulon of P. salmonis.
  
  
  CONCLUSIONS
  This study revealed, for the first time, differences in the transcriptional response to P. salmonis infection among Atlantic salmon families with varied levels of susceptibility to the infection. These differences correlated with changes in the abundance of transcripts encoding proteins directly and indirectly involved in the immune response; changes that highlighted the role of nutritional immunity through iron deprivation in host defence mechanisms against P. salmonis. Additionally, we found that P. salmonis has several mechanisms for iron acquisition, suggesting that this bacterium can obtain iron from different sources, including ferric iron through capturing endogenous and exogenous siderophores and ferrous iron. Our results contribute to determining the underlying resistance mechanisms of Atlantic salmon to P. salmonis infection and to identifying future treatment strategies.
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, El Líbano 5524, Santiago, Chile. rpulgar@inta.uchile.cl.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pulgar
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, El Líbano 5524, Santiago, Chile. chodar@inta.uchile.cl.|Fondap Center for Genome Regulation, Av. Blanco Encalada 2085, Santiago, Chile. chodar@inta.uchile.cl.
authors.forename: Christian
authors.initials: C
authors.lastname: Hödar
authors.affiliation: Fondap Center for Genome Regulation, Av. Blanco Encalada 2085, Santiago, Chile. dtravisany@dim.uchile.cl.|Center for Mathematical Modeling and Department of Mathematical Engineering, Av. Beauchef 851, Santiago, Chile. dtravisany@dim.uchile.cl.
authors.forename: Dante
authors.initials: D
authors.lastname: Travisany
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, El Líbano 5524, Santiago, Chile. jano@inta.uchile.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zuñiga
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, El Líbano 5524, Santiago, Chile. cdportilla@gmail.com.
authors.forename: Calixto
authors.initials: C
authors.lastname: Domínguez
authors.affiliation: Fondap Center for Genome Regulation, Av. Blanco Encalada 2085, Santiago, Chile. amaass@dim.uchile.cl.|Center for Mathematical Modeling and Department of Mathematical Engineering, Av. Beauchef 851, Santiago, Chile. amaass@dim.uchile.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Maass
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, El Líbano 5524, Santiago, Chile. mgonzale@inta.uchile.cl.|Fondap Center for Genome Regulation, Av. Blanco Encalada 2085, Santiago, Chile. mgonzale@inta.uchile.cl.
authors.forename: Mauricio
authors.initials: M
authors.lastname: González
authors.affiliation: Laboratorio de Bioinformática y Expresión Génica, Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, El Líbano 5524, Santiago, Chile. vcambiaz@inta.cl.|Fondap Center for Genome Regulation, Av. Blanco Encalada 2085, Santiago, Chile. vcambiaz@inta.cl.
authors.forename: Verónica
authors.initials: V
authors.lastname: Cambiazo
mesh_terms: D000818:Animals; D004198:Disease Susceptibility / Q000378:metabolism / Q000382:microbiology; D005393:Fish Diseases / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D053522:Piscirickettsia / Q000472:pathogenicity*; D044225:Piscirickettsiaceae Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D020317:Salmo salar / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D007501:Iron