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Francisella tularensis subspecies holarctica´s adaptation to protozoan and mammal hosts
Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.ORCID iD: 0000-0001-5601-9358
Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, SE-901 82 Umeå, Sweden.
Division of CBRN Defence and Security, Swedish Defence Research Agency, FOI, SE-901 82 Umeå, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The long co-existence of bacteria and protozoa in natural ecosystems has led to the evolution of different bacterial predation-resistance mechanisms1, which in turn may have triggered development of mammal pathogens2, such as the tularemia bacterium Francisella tularensis3. We studied links between environmental persistence and pathogenicity of Francisella tularensis subsp. holarctica (F. t. holarctica), by comparing its growth in association with an aquatic amoeba and a murine macrophage. A virulent wild-type strain and four isogenic mutations with different functional protein deletions were compared; DsbA4, 5 a membrane lipoprotein with disulfide oxidoreductase activity important for proper folding in Francisella tularensis; Hfq6 a pleiotropic regulatory RNA binding protein; PilA7, 8 a type IV pilus subunit and PglA9 a protein involved in O-linked protein glycosylation. DsbA was found to be essential for bacterial growth in association with both amoeba and macrophage, while PglA did not affect bacterial persistence in any of the hosts. Absence of PilA and Hfq had marked negative effect on the bacterial cell counts in amoeba, while growth was only slightly impaired in the macrophage. Functional similarities for bacterial persistence in both hosts highlight eco-evolutionary links between persistence of intracellular pathogenic bacteria in aquatic systems and mammal hosts.

National Category
Ecology
Identifiers
URN: urn:nbn:se:umu:diva-133337OAI: oai:DiVA.org:umu-133337DiVA: diva2:1087107
Funder
Ecosystem dynamics in the Baltic Sea in a changing climate perspective - ECOCHANGESwedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 217-2008-1443Swedish Research Council, 60276201
Note

Medfinansiär var även: Swedish Ministry of Defence [A404215]

Available from: 2017-04-05 Created: 2017-04-05 Last updated: 2017-04-06
In thesis
1. Environmental factors selecting for predation resistant and potentially pathogenic bacteria in aquatic environments
Open this publication in new window or tab >>Environmental factors selecting for predation resistant and potentially pathogenic bacteria in aquatic environments
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The long history of co-existence of bacteria and their protozoan predators in aquatic environments has led to evolution of protozoa resistant bacteria (PRB). Many of these bacteria are also pathogenic to humans. However, the ecological drivers determining the occurrence of different types of PRB in aquatic environments, and the eco-evolutionary link between bacterial adaptation and the resulting implications for mammalian hosts are poorly known. This thesis examines the impact of nutrients and predation on PRB, as well as the ecological and evolutionary connection between their life in aquatic environments and mammalian hosts. In the first study seven bacterial isolates from the Baltic Sea were investigated for their plasticity of adaptation to predation. The response to predation showed large variation where some bacteria rapidly developed a degree of grazing resistance when exposed to predators. The rapid adaptation observed may result in bacterial communities being resilient or resistant to predation, and thus rapid adaptation may be a structuring force in the food web. With the aim to elucidate the link between occurrence of PRB and environmental conditions, a field study and a laboratory experiment were performed. In both studies three PRB genera were found: Mycobacterium, Pseudomonas and Rickettsia. PRB were found both in oligotrophic and eutrophic waters, indicating that waters of all nutrient states can harbor pathogenic bacteria. However, the ecological strategy of the PRB varied depending on environmental nutrient level and disturbance. Using an advanced bioinformatic analysis, it was shown that ecotypes within the same PRB genus can be linked to specific environmental conditions or the presence of specific protozoa, cyanobacteria or phytoplankton taxa. These environmental conditions or specific plankton taxa could potentially act as indicators for occurrence of PRB. Finally, using four mutants (with specific protein deletions) of the pathogenic and predation resistant Francisella tularensis ssp. holarctica, I found evidence of an eco-evolutionary connection between the bacterium´s life in aquatic and mammalian hosts (aquatic amoeba Acanthamoeba castellanii and a murine macrophage).  To a large extent F. t. holarctica use similar mechanisms to persist predation by protozoa and to resist degradation by mammal macrophages. To summarize I found a link between predation resistant bacteria in aquatic environments and bacteria that are pathogenic to mammals. Further, I showed that different environmental conditions rapidly selects for PRB with either intracellular or extracellular lifestyles. This thesis provides insights regarding environmental conditions and biomarkers that can be used for assessment of aquatic environments at risk for spreading pathogenic bacteria.  

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2017. 28 p.
Keyword
Eutrophication, productivity, predation pressure, predation-resistant bacteria, pathogens, Francisella tularensis, adaptation, biomarker, oligotyping
National Category
Ecology
Identifiers
urn:nbn:se:umu:diva-133338 (URN)978-91-7601-684-8 (ISBN)
Public defence
2017-04-28, Lilla Hörsalen, KB3A9, Chemical Biological Center (KBC), Umeå Universitet, Umeå, 12:30 (English)
Opponent
Supervisors
Funder
Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 217-2008-1443Swedish Research Council, 60276201Ecosystem dynamics in the Baltic Sea in a changing climate perspective - ECOCHANGE
Note

Medfinansiärer var även: Swedish Ministry of Defence (A4040, A4042, A404215, A404217), Swedish Minestry of Foreign Affairs (A4952), Swedish Civil Contingencies Agency (B4055)

Available from: 2017-04-07 Created: 2017-04-05 Last updated: 2017-05-10Bibliographically approved

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