Host genetic variation explains reduced protection of commercial vaccines against Piscirickettsia salmonis in Atlantic salmon
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ABSTRACT:
SUBMITTER: Figueroa C
PROVIDER: S-EPMC7588420 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:In Atlantic salmon, vaccines have failed to control and prevent Piscirickettsiosis, for reasons that remain elusive. In this study, we report the efficacy of two commercial vaccines developed with the Piscirickettsia salmonis isolates AL100005 and AL 20542 against another two genogroups which are considered highly and ubiquitously prevalent in Chile: LF-89 and EM-90. Two cohabitation trials were performed to mimic field conditions and vaccine performance: (1) post-smolt fish were challenged with a single infection of LF-89, (2) adults were coinfected with EM-90, and a low level coinfection of sea lice. In the first trial, the vaccine delayed smolt mortalities by two days; however, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 60.3%, vaccinated: 56.7%; p = 0.28). In the second trial, mortality started three days later for vaccinated fish than unvaccinated fish. However, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 64.6%, vaccinated: 60.2%, p = 0.58). Thus, we found no evidence that the evaluated vaccines confer effective protection against the genogroups LF-89 and EM-90 of P. salmonis with estimated relative survival proportions (RPSs) of -9% and -12%, respectively. More studies are necessary to evaluate whether pathogen heterogeneity is a key determinant of the lack of vaccine efficacy against P. salmonis.
| S-EPMC9312220 | biostudies-literature
Project description:The aquaculture industry has confronted severe economic losses due to infectious diseases in the last years. Piscirickettsiosis or Salmonid Rickettsial Septicaemia (SRS) is the bacterial disease caused by Piscirickettsia salmonis. This Gram-negative, non-motile, cellular pathogen has the ability to infect, survive, replicate, and propagate in salmonid monocytes/macrophages generating a systemic infection characterized by the colonization of several organs including kidney, liver, spleen, intestine, brain, ovary and gills. In this study, we attempted to determine whether global gene expression differences can be detected in different genetic groups of Atlantic salmon as a result of Piscirickettsia salmonis infection. Moreover, we sought to characterize the fish transcriptional response in order to reveal the mechanisms that might confer resistance in Atlantic salmon to an infection with Piscirickettsia salmonis. In doing so, after challenging with Piscirickettsia salmonis, we selected the families with the highest (HS) and the lowest (LS) recorded susceptibility for gene expression analysis using 32K cGRASP microarrays. Our results revealed in LS families expression changes are linked to iron depletion, as well as, low contents of iron in kidney cells and low bacterial load, indicated that the iron-withholding strategy of innate immunity is part of the mechanism of resistance against Piscirickettsia salmonis. This information contributes to elucidate the underlying mechanisms of resistance to Piscirickettsia salmonis infection in Atlantic salmon and to identify new candidate genes for selective breeding programmes.
2013-01-04 | GSE43255 | GEO
Project description:The aquaculture industry has confronted severe economic losses due to infectious diseases in the last years. Piscirickettsiosis or Salmonid Rickettsial Septicaemia (SRS) is the bacterial disease caused by Piscirickettsia salmonis. This Gram-negative, non-motile, cellular pathogen has the ability to infect, survive, replicate, and propagate in salmonid monocytes/macrophages generating a systemic infection characterized by the colonization of several organs including kidney, liver, spleen, intestine, brain, ovary and gills. In this study, we attempted to determine whether global gene expression differences can be detected in different genetic groups of Atlantic salmon as a result of Piscirickettsia salmonis infection. Moreover, we sought to characterize the fish transcriptional response in order to reveal the mechanisms that might confer resistance in Atlantic salmon to an infection with Piscirickettsia salmonis. In doing so, after challenging with Piscirickettsia salmonis, we selected the families with the highest (HS) and the lowest (LS) recorded susceptibility for gene expression analysis using 32K cGRASP microarrays. Our results revealed in LS families expression changes are linked to iron depletion, as well as, low contents of iron in kidney cells and low bacterial load, indicated that the iron-withholding strategy of innate immunity is part of the mechanism of resistance against Piscirickettsia salmonis. This information contributes to elucidate the underlying mechanisms of resistance to Piscirickettsia salmonis infection in Atlantic salmon and to identify new candidate genes for selective breeding programmes. Forty full-sibling families of Atlantic salmon (Salmo salar) were infected by intraperitoneal injection with 0.2 mL Piscirickettsia salmonis (PS889, isolated from Oncorhynchus kisutch, 1M-CM-^W104 PFU/mL). After forty days, the fishes were harvested and the cumulative mortality (dead fish / total fish) for each family was calculated. For the second challenge, the six families with the highest cumulative mortality levels were considered of relatively high susceptibility (HS) and the six families with the lowest cumulative mortality levels were considered of relatively low susceptibility (LS) to the infection. Five control and five infected fish from three HS and three LS families were analyzed. For each HS and LS family, pools of RNA from control and infected fish were prepared separately and were reverse transcribed. Four slides were for each used family hybridized including two dye-swaped slides. Labeled samples were hybridized on a 32K cDNA microarray, developed at the Consortium for Genomics Research on All Salmonids Project (cGRASP), GEO accession number: GPL8904.
2013-01-04 | E-GEOD-43255 | biostudies-arrayexpress
Project description:Secretion of extracellular vesicles (EVs) is a common feature of both eukaryotic and prokaryotic cells. Isolated EVs have been shown to contain different types of molecules, including proteins and nucleic acids, and are reported to be key players in intercellular communication. Little is known, however, of EV secretion in fish, or the effect of infection on EV release and content. In the present study, EVs were isolated from the serum of healthy and Piscirickettsia salmonis infected Atlantic salmon in order to evaluate the effect of infection on EV secretion. P. salmonis is facultative intracellular bacterium that causes a systemic infection disease in farmed salmonids. EVs isolated from both infected and non-infected fish had an average diameter of 230-300 nm, as confirmed by transmission electron microscopy, nanoparticle tracking, and flow cytometry. Mass spectrometry identified 180 proteins in serum EVs from both groups of fish. Interestingly, 35 unique proteins were identified in serum EVs isolated from the fish infected with P. salmonis. These unique proteins included proteasomes subunits, granulins, and major histocompatibility class I and II. Our results suggest that EV release could be part of a mechanism in which host stimulatory molecules are released from infected cells to promote an immune response.
| S-EPMC5748569 | biostudies-literature
Project description:Piscirickettsia salmonis, an aggressive intracellular pathogen, is the etiological agent of salmonid rickettsial septicemia (SRS). This is a chronic multisystemic disease that generates high mortalities and large losses in Chilean salmon farming, threatening the sustainability of the salmon industry. Previous reports suggest that P. salmonis is able to survive and replicate in salmonid macrophages, inducing an anti-inflammatory environment and a limited lysosomal response that may be associated with host immune evasion mechanisms favoring bacterial survival. Current control and prophylaxis strategies against P. salmonis (based on the use of antibiotics and vaccines) have not had the expected success against infection. This makes it urgent to unravel the host-pathogen interaction to develop more effective therapeutic strategies. In this study, we evaluated the effect of treatment with IgM-beads on lysosomal activity in Atlantic salmon macrophage-enriched cell cultures infected with P. salmonis by analyzing the lysosomal pH and proteolytic ability through confocal microscopy. The impact of IgM-beads on cytotoxicity induced by P. salmonis in infected cells was evaluated by quantification of cell lysis through release of Lactate Dehydrogenase (LDH) activity. Bacterial load was determined by quantification of 16S rDNA copy number by qPCR, and counting of colony-forming units (CFU) present in the extracellular and intracellular environment. Our results suggest that stimulation with antibodies promotes lysosomal activity by lowering lysosomal pH and increasing the proteolytic activity within this organelle. Additionally, incubation with IgM-beads elicits a decrease in bacterial-induced cytotoxicity in infected Atlantic salmon macrophages and reduces the bacterial load. Overall, our results suggest that stimulation of cells infected by P. salmonis with IgM-beads reverses the modulation of the lysosomal activity induced by bacterial infection, promoting macrophage survival and bacterial elimination. This work represents a new important evidence to understand the bacterial evasion mechanisms established by P. salmonis and contribute to the development of new effective therapeutic strategies against SRS.
| S-EPMC7688784 | biostudies-literature
Project description:An effective and economical vaccine against the Piscirickettsia salmonis pathogen is needed for sustainable salmon farming and to reduce disease-related economic losses. Consequently, the aquaculture industry urgently needs to investigate efficient prophylactic measures. Three protein-based vaccine prototypes against Piscirickettsia salmonis were prepared from a highly pathogenic Chilean isolate. Only one vaccine effectively protected Atlantic salmon (Salmo salar), in correlation with the induction of Piscirickettsia-specific IgM antibodies and a high induction of transcripts encoding pro-inflammatory cytokines (i.e., Il-1β and TNF-α). In addition, we studied the proteome fraction protein of P. salmonis strain Austral-005 using multidimensional protein identification technology. The analyzes identified 87 proteins of different subcellular origins, such as the cytoplasmic and membrane compartment, where many of them have virulence functions. The other two prototypes activated only the innate immune responses, but did not protect Salmo salar against P. salmonis. These results suggest that the knowledge of the formulation of vaccines based on P. salmonis proteins is useful as an effective therapy, this demonstrates the importance of the different research tools to improve the study of the different immune responses, resistance to diseases in the Atlantic salmon. We suggest that this vaccine can help prevent widespread infection by P. salmonis, in addition to being able to be used as a booster after a primary vaccine to maintain high levels of circulating protective antibodies, greatly helping to reduce the economic losses caused by the pathogen.
| S-EPMC7927424 | biostudies-literature
Project description:BackgroundVertebrate hosts limit the availability of iron to microbial pathogens in order to nutritionally starve the invaders. The impact of iron deficiency induced by the iron chelator deferoxamine mesylate (DFO) was investigated in Atlantic salmon SHK-1 cells infected with the facultative intracellular bacterium Piscirickettsia salmonis.ResultsEffects of the DFO treatment and P. salmonis on SHK-1 cells were gaged by assessing cytopathic effects, bacterial load and activity, and gene expression profiles of eight immune biomarkers at 4- and 7-days post infection (dpi) in the control group, groups receiving single treatments (DFO or P. salmonis) and their combination. The chelator appears to be well-tolerated by host cells, while it had a negative impact on the number of bacterial cells and associated cytotoxicity. DFO alone had minor effects on gene expression of SHK-1 cells, including an early activation of IL-1β at 4 dpi. In contrast to few moderate changes induced by single treatments (either infection or chelator), most genes had highest upregulation in the infected groups receiving DFO. The mildest induction of hepcidin-1 (antimicrobial peptide precursor and regulator of iron homeostasis) was observed in cells exposed to DFO alone, followed by P. salmonis infected cells while the addition of DFO to infected cells further increased the mRNA abundance of this gene. Transcripts encoding TNF-α (immune signaling) and iNOS (immune effector) showed sustained increase at both time points in this group while cathelicidin-1 (immune effector) and IL-8 (immune signaling) were upregulated at 7 dpi. The stimulation of protective gene responses seen in infected cultures supplemented with DFO coincided with the reduction of bacterial load and activity (judged by the expression of P. salmonis 16S rRNA), and damage to cultured host cells.ConclusionThe absence of immune gene activation under normal iron conditions suggests modulation of host responses by P. salmonis. The negative effect of iron deficiency on bacteria likely allowed host cells to respond in a more protective manner to the infection, further decreasing its progression. Presented findings encourage in vivo exploration of iron chelators as a promising strategy against piscirickettsiosis.
| S-EPMC8043062 | biostudies-literature
Project description:An effective and economical vaccine against the Piscirickettsia salmonis pathogen is needed for sustainable salmon farming and to reduce disease-related economic losses. Consequently, the aquaculture industry urgently needs to investigate efficient prophylactic measures. Three protein-based vaccine prototypes against Piscirickettsia salmonis were prepared from a highly pathogenic Chilean isolate. Only one vaccine effectively protected Atlantic salmon (Salmo salar), in correlation with the induction of Piscirickettsia-specific IgM antibodies and a high induction of transcripts encoding pro-inflammatory cytokines (i.e. Il-1β and TNF-α). In addition, we studied the proteome fraction protein of P. salmonis strain Austral-005 using multidimensional protein identification technology. The analyzes identified 87 proteins of different subcellular origins, such as the cytoplasmic and membrane compartment, where many of them have virulence functions. The other two prototypes activated only the innate immune responses, but did not protect Salmo salar against Piscirickettsia salmonis. These results suggest that the knowledge of the formulation of vaccines based on P. salmonis proteins is useful as an effective therapy, this demonstrates the importance of the different research tools to improve the study of the different immune responses, resistance to diseases in the Atlantic salmon. We suggest that this vaccine can help prevent widespread infection by P. salmonis, in addition to being able to be used as a booster after a primary vaccine to maintain high levels of circulating protective antibodies, greatly helping to reduce the economic losses caused by the pathogen.
2021-02-16 | PXD023109 | Pride
Project description:High-throughput sequencing technologies have offered the possibility to understand the complexity of the transcriptomic responses of an organism during a wide variety of biological scenarios, such as the case of pathogenic infections. Recently, the simultaneous sequencing of both pathogen and host transcriptomes (dual RNA-seq) during the infection has become a promising approach to uncover the complexity of the host-pathogen interactions. In this study, through a double rRNA depletion and RNA sequencing protocols, we simultaneously analyzed the transcriptome of the intracellular bacterium Piscirickettsia salmonis and its host the Atlantic salmon (Salmo salar) during the course of the infection. Beyond canonical host immune-related response and pathogen virulent factors, both bacteria and host displayed a large number of genes associated with metabolism and particularly related with the amino acid metabolism. Notably, genome-wide comparison among P. salmonis genomes and different fish pathogens genomes revealed a lack of the biosynthetic pathway for several amino acids such as valine, leucine, and isoleucine. To support this finding, in vitro experiments evidenced that when these amino acids are restricted the bacterial growth dynamics is significantly affected. However, this condition is phenotypically reversed when the amino acids are supplemented in the bacterial growth medium. Based on our results, a metabolic dependency of P. salmonis on S. salar amino acids is suggested, which could imply novel mechanisms of pathogenesis based on the capacity to uptake nutrients from the host. Overall, dual transcriptome sequencing leads to the understanding of host-pathogen interactions from a different perspective, beyond biological processes related to immunity.
| S-EPMC6277808 | biostudies-literature
Project description:This experiment was aimed at understanding the early transcriptional response to the salmon pathogen Piscirikettsia salmonis at 48h post infection in multiple tissues. Agilent-based microarray platform with 4 44 K probes per slide (Salar_2; Agilent Design ID:025520) oligo microarray was used in this experiment. A dual-labelled experimental design was employed for the microarray hybridisations. aRNA from each experimental sample (Cy3 labelled) was competitively hybridised against a common pooled-reference sample (Cy5 labelled), which comprised equal amounts of aRNA from each of the samples used in the study. This design permits valid statistical comparisons across all treatments to be made. The entire experiment comprised 24 hybridisations - 3 tissues (head kidney, liver, muscle) 2 treatments (SRS injection / saline control injection) 4 biological replicates.
2012-05-01 | E-MTAB-685 | biostudies-arrayexpress