uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The genome of Spironucleus salmonicida highlights a fish pathogen adapted to fluctuating environments
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Show others and affiliations
2014 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 2, p. e1004053-Article in journal (Refereed) Published
Abstract [en]

Spironucleus salmonicida causes systemic infections in salmonid fish. It belongs to the group diplomonads, binucleated heterotrophic flagellates adapted to micro-aerobic environments. Recently we identified energy-producing hydrogenosomes in S. salmonicida. Here we present a genome analysis of the fish parasite with a focus on the comparison to the more studied diplomonad Giardia intestinalis. We annotated 8067 protein coding genes in the ∼12.9 Mbp S. salmonicida genome. Unlike G. intestinalis, promoter-like motifs were found upstream of genes which are correlated with gene expression, suggesting a more elaborate transcriptional regulation. S. salmonicida can utilise more carbohydrates as energy sources, has an extended amino acid and sulfur metabolism, and more enzymes involved in scavenging of reactive oxygen species compared to G. intestinalis. Both genomes have large families of cysteine-rich membrane proteins. A cluster analysis indicated large divergence of these families in the two diplomonads. Nevertheless, one of S. salmonicida cysteine-rich proteins was localised to the plasma membrane similar to G. intestinalis variant-surface proteins. We identified S. salmonicida homologs to cyst wall proteins and showed that one of these is functional when expressed in Giardia. This suggests that the fish parasite is transmitted as a cyst between hosts. The extended metabolic repertoire and more extensive gene regulation compared to G. intestinalis suggest that the fish parasite is more adapted to cope with environmental fluctuations. Our genome analyses indicate that S. salmonicida is a well-adapted pathogen that can colonize different sites in the host.

Place, publisher, year, edition, pages
2014. Vol. 10, no 2, p. e1004053-
National Category
Microbiology Genetics
Identifiers
URN: urn:nbn:se:uu:diva-224545DOI: 10.1371/journal.pgen.1004053ISI: 000332021500041PubMedID: 24516394OAI: oai:DiVA.org:uu-224545DiVA, id: diva2:717105
Available from: 2014-05-14 Created: 2014-05-14 Last updated: 2019-03-19Bibliographically approved
In thesis
1. Comparative Genomics in Diplomonads: Lifestyle Variations Revealed at Genetic Level
Open this publication in new window or tab >>Comparative Genomics in Diplomonads: Lifestyle Variations Revealed at Genetic Level
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

As sequencing technologies advance genome studies are becoming a basic tool for studying an organism, and with more genomes available comparative genomics is maturing into a powerful tool for biological research. This thesis demonstrates the strength of a comparative genomics approach on a group of understudied eukaryotes, the diplomonads.

Diplomonads are a group of single cell eukaryotic flagellates living in oxygen-poor environments. Most diplomonads are intestinal parasites, like the well-studied human parasite Giardia intestinalis. There are seven different G. intestinalis assemblages (genotypes) affecting different hosts, and it’s under debate whether these are one species. A genome-wide study of three G. intestinalis genomes from different assemblages reveals little inter-assemblage sexual recombination, supporting that the different G. intestinalis assemblages are genetically isolated and thus different species.

A genomic comparison between the fish parasite S. salmonicida and G. intestinalis reveals genetic differences reflecting differences in their parasitic lifestyles. There is a tighter transcriptional regulation and a larger metabolic reservoir in S. salmonicida, likely adaptations to the fluctuating environments it encounters during its systemic infection compared to G. intestinalis which is a strict intestinal parasite.

The S. salmonicida genome analysis also discovers genes involved in energy metabolism. Some of these are experimentally shown to localize to mitochondrion-related organelles in S. salmonicida, indicating that they possess energy-producing organelles that should be classified as hydrogenosomes, as opposed to the mitosomes in G. intestinalis.

A transcriptome analysis of the free-living Trepomonas is compared with genomic data from the two parasitic diplomonads. The majority of the genes associated with a free-living lifestyle, like phagocytosis and a larger metabolic capacity, are of prokaryotic origin. This suggests that the ancestor of the free-living diplomonad was likely host-associated and that the free-living lifestyle is a secondary adaptation acquired through horizontal gene transfers. 

In conclusion, this thesis uses different comparative genomics approaches to broaden the knowledge on diplomonad diversity and to provide more insight into how the lifestyle differences are reflected on the genetic level. The bioinformatics pipelines and expertise gained in these studies will be useful in other projects in diplomonads and other organismal groups.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. p. 64
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1261
Keywords
comparative genomics, Giardia intestinalis, Spironucleus salmonicida, Trepomonas, diplomonad, intestinal parasite, free-living, sexual recombination, hydrogenosome, horizontal gene transfer
National Category
Bioinformatics and Systems Biology Evolutionary Biology Microbiology
Research subject
Biology with specialization in Molecular Evolution
Identifiers
urn:nbn:se:uu:diva-251650 (URN)978-91-554-9262-5 (ISBN)
Public defence
2015-06-12, BMC, B41, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2015-05-22 Created: 2015-04-23 Last updated: 2015-07-07Bibliographically approved
2. Pathogenesis and Cell Biology of the Salmon Parasite Spironucleus salmonicida
Open this publication in new window or tab >>Pathogenesis and Cell Biology of the Salmon Parasite Spironucleus salmonicida
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spironucleus species are classified as diplomonad organisms, diverse eukaryotic flagellates found in oxygen-deprived environments. Members of Spironucleus are parasitic and can infect a variety of hosts, such as mice and birds, while the majority are found to infect fish. Massive outbreaks of severe systemic infection caused by a Spironucleus member, Spironucleus salmonicida (salmonicida = salmon killer), have been reported in farmed salmonids resulting in large economic impacts for aquaculture.

In this thesis, the S. salmonicida genome was sequenced and compared to the genome of its diplomonad relative, the mammalian pathogen G. intestinalis (Paper I). Our analyses revealed large genomic differences between the two parasites that collectively suggests that S. salmonicida is more capable of adapting to different environments. As S. salmonicida can infiltrate different host tissues, we provide molecular evidence for how the parasite can tolerate oxygenated environments and suggest oxygen as a potential regulator of virulence factors (Paper III). To further investigate the molecular responses of the parasite and in addition, its host, during infection we set up an interaction system of S. salmonicida and ASK (Atlantic salmon kidney) cells (Paper VI).

To study the cell biology in S. salmonicida we optimized an enzymatic proximity labeling method using ascorbate peroxidase (APEX) as a reporter for transmission electron microscopy (TEM) (Paper IV). As the system is robust and versatile, we showed the localization and performed ultrastructural characterization of numerous proteins in S. salmonicida and G. intestinalis. We furthermore utilized the APEX system to study the annexin protein family in S. salmonicida (Paper II). Super resolution microscopy and TEM were applied to show that the annexins are mostly associated with cytoskeletal and membranous structures. In addition, we performed phylogenetic analyses concluding that the annexin gene family is expanded in diplomonads.

We performed experimental infection in Atlantic salmon and derived a potential model for the route of infection (Paper V). The results suggested multiple routes of transmission between hosts for the parasite.

To conclude, the comprehensive work in this thesis has provided valuable insights into the pathogenesis and cell biology of the highly adaptable diplomonad parasite S. salmonicida.      

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 70
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1785
Keywords
Diplomonads, Spironucleus, Giardia, genome, annexin, oxygen stress, APEX, pathology
National Category
Microbiology
Identifiers
urn:nbn:se:uu:diva-379671 (URN)978-91-513-0604-9 (ISBN)
Public defence
2019-05-10, A1:111a, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Swedish Research Council Formas
Available from: 2019-04-17 Created: 2019-03-19 Last updated: 2019-06-18

Open Access in DiVA

fulltext(2900 kB)394 downloads
File information
File name FULLTEXT01.pdfFile size 2900 kBChecksum SHA-512
6247a1f07a716a1d4c06da45a92862fac7f9739d2c02a38ba66e9ef839555886a6c46ecbaf34faca04c0d4e5c17bc4750f37283a68ce1230d5790a839d1ae18b
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Xu, FeifeiJerlström-Hultqvist, JonEinarsson, ElinAstvaldsson, AsgeirSvärd, Staffan GAndersson, Jan O

Search in DiVA

By author/editor
Xu, FeifeiJerlström-Hultqvist, JonEinarsson, ElinAstvaldsson, AsgeirSvärd, Staffan GAndersson, Jan O
By organisation
Molecular EvolutionScience for Life Laboratory, SciLifeLabDepartment of Cell and Molecular BiologyMicrobiology
In the same journal
PLoS Genetics
MicrobiologyGenetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 394 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 1127 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf