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  • 1. Beldowski, Jacek
    et al.
    Klusek, Zygmunt
    Szubska, Marta
    Turja, Raisa
    Bulczak, Anna I.
    Rak, Daniel
    Brenner, Matthias
    Lang, Thomas
    Kotwicki, Lech
    Grzelak, Katarzyna
    Jakacki, Jaromir
    Fricke, Nicolai
    Ostin, Anders
    Olsson, Ulf
    Fabisiak, Jacek
    Garnaga, Galina
    Nyholm, Jenny Rattfelt
    Majewski, Piotr
    Broeg, Katja
    Soderstrom, Martin
    Vanninen, Paula
    Popiel, Stanislaw
    Nawala, Jakub
    Lehtonen, Kari
    Berglind, Rune
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Schmidt, Beata
    Chemical Munitions Search & Assessment-An evaluation of the dumped munitions problem in the Baltic Sea2016In: Deep-sea research. Part II, Topical studies in oceanography, ISSN 0967-0645, E-ISSN 1879-0100, Vol. 128, p. 85-95Article in journal (Refereed)
    Abstract [en]

    Chemical Munitions Search & Assessment (CHEMSEA) project has performed studies on chemical weapon (CW) detection, sediment pollution and spreading as well as biological effects of chemical warfare agents (CWAs) dumped in the Baltic Sea. Results suggest that munitions containing CWAs are more scattered on the seafloor than suspected, and previously undocumented dumpsite was discovered in Gdansk Deep. Pollution of sediments with CWA degradation products was local and close to the detected objects; however the pollution range was larger than predicted with theoretical models. Bottom currents observed in the dumpsites were strong enough for sediment re-suspension, and contributed to the transport of polluted sediments. Diversity and density of the faunal communities were poor at the dumping sites in comparison to the reference area, although the direct effects of CWA on benthos organisms were difficult to determine due to hypoxic or even anoxic conditions near the bottom. Equally, the low oxygen might have affected the biological effects assessed in cod and caged blue mussels. Nonetheless, both species showed significantly elevated molecular and cellular level responses at contaminated sites compared to reference sites.

  • 2.
    Berg, Lotta
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Niemiec, Moritz S.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Qian, Weixing
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Andersson, C. David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wittung-Stafshede, Pernilla
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ekström, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Similar but Different: Thermodynamic and Structural Characterization of a Pair of Enantiomers Binding to Acetylcholinesterase2012In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 51, no 51, p. 12716-12720Article in journal (Refereed)
    Abstract [en]

    Take a closer look: Unexpectedly, a pair of enantiomeric ligands proved to have similar binding affinities for acetylcholinesterase. Further studies indicated that the enantiomers exhibit different thermodynamic profiles. Analyses of the noncovalent interactions in the protein-ligand complexes revealed that these differences are partly due to nonclassical hydrogen bonds between the ligands and aromatic side chains of the protein.

  • 3.
    Berglind, Rune
    et al.
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Leffler, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Interactions between pH, potassium, calcium, bromide, and phenol and their effects on the bioluminescence of Vibrio fischeri2010In: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 73, no 16, p. 1102-1112Article in journal (Refereed)
    Abstract [en]

    Little attention has been paid to how the light produced by the bacterium Vibrio fischeri in the Microtox assay is dependent on the concentration of essential ions such as sodium and potassium, and whether the concentrations of these ions affect the sensitivity of the test system to toxic chemicals. Five selected factors, pH, potassium (K(+)), calcium (Ca(2+)), bromide (Br(-)), and phenol (Phe), were simultaneously varied over a set of systematically planned experiments according to a D-optimal design that supported the estimation of a model with linear, quadratic, and two-factor interatcions of the studied factors. The bacterial light production represented by the gamma values in the Microtox assay for the 24 selected combinations of factors was measured at 5 and 15 min. The gamma values varied from negative to positive values greater than 1, indicating stimulation and inhibition of bacterial light production, respectively. The relationship between the gamma values and the factor settings was investigated with multiple linear regression. After 5 min of exposure, the light production was significantly affected by linear and quadratic terms for K(+), pH, and Phe and an interaction between pH and Phe. The situation was more complex after 15 min of exposure, since in addition significant interactions were found for K x Phe and Ca x pH. The tolerance of V. fischeri to Phe was enhanced by increasing the K and Ca concentrations. Data indicate that the ion composition and pH of the sample, as well as the diluents, need to be considered when the toxicity of salts, water samples, and extracts of sediments and soils are tested using commercially certified toxicity test kits.

  • 4.
    Bystrom, Julia Wigren
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Näslund, Jonas
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Trulsson, Fredrik
    Umeå University, Faculty of Science and Technology, European CBRNE Center. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wesula Lwande, Olivia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bucht, Göran
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Quantification and kinetics of viral RNA transcripts produced in Orthohantavirus infected cells2018In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 15, p. 1-7, article id 18Article in journal (Refereed)
    Abstract [en]

    Background: Rodent borne viruses of the Orthohantavirus genus cause hemorrhagic fever with renal syndrome among people in Eurasia, and hantavirus cardiopulmonary syndrome in the Americas. At present, there are no specific treatments or efficient vaccines against these diseases. Improved understanding of viral transcription and replication may instigate targeted treatment of Orthohantavirus infections. For this purpose, we investigated the kinetics and levels of viral RNA transcription during an ongoing infection in-vitro. Methods: Vero E6 cells were infected with Puumala Orthohantavirus (strain Kazan) before cells and supernatants were collected at different time points post infection for the detection of viral RNAs. A plasmid containing primer binding sites of the three Orthohantavirus segments small (S), medium (M) and large (L) was constructed and standard curves were generated to calculate the copy numbers of the individual transcripts in the collected samples. Results: Our results indicated a rapid increase in the copy number of viral RNAs after 9 h post infection. At peak days, 2-6 days after infection, the S- and M-segment transcripts became thousand and hundred-fold more abundant than the copy number of the L-segment RNA, respectively. The presence of viral RNA in the cell culture media was detected at later time-points. Conclusions: We have developed a method to follow RNA transcription in-vitro after synchronous infection of Vero cells. The obtained results may contribute to the understanding of the viral replication, and may have implications in the development of antiviral drugs targeting transcription or replication of negative stranded RNA viruses.

  • 5.
    Franzén, Oscar
    et al.
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Lindstein, Daniel
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Förutsättningar för inplantering av fisk i svenska insjöar: med Hissjön som exempel2009Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 6.
    Gunnarsson, David
    et al.
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Leffler, Per
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Ekwurtzel, Emelie
    Martinsson, Gunilla
    Liu, Kui
    Umeå University, Faculty of Medicine, Medical Biochemistry and Biophsyics.
    Selstam, Gunnar
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes2008In: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 135, no 5, p. 693-703Article in journal (Refereed)
    Abstract [en]

    Phthalates are widely used as plasticizers in a number of daily-life products. In this study, we investigated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the frequently used plasticizer di-(2-ethylhexyl) phthalate (DEHP), on gonadal steroidogenesis in vitro. MEHP (25–100 µM) stimulated basal steroid synthesis in a concentration-dependent manner in immortalized mouse Leydig tumor cells (MLTC-1). The stimulatory effect was also detected in KK-1 granulosa tumor cells. MEHP exposure did not influence cAMP or StAR protein levels and induced a gene expression profile of key steroidogenic proteins different from the one induced by human chorionic gonadotropin (hCG). Simultaneous treatment with MEHP and a p450scc inhibitor (aminoglutethimide) indicated that MEHP exerts its main stimulatory effect prior to pregnenolone formation. MEHP (10–100 µM) up-regulated hormone-sensitive lipase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, suggesting that MEHP increases the amount of cholesterol available for steroidogenesis. Our data suggest that MEHP, besides its known inhibitory effect on hCG action, can directly stimulate gonadal steroidogenesis in both sexes through a cAMP- and StAR-independent mechanism. The anti-steroidogenic effect of DEHP has been proposed to cause developmental disorders such as hypospadias and cryptorchidism, whereas a stimulation of steroid synthesis may prematurely initiate the onset of puberty and theoretically affect the hypothalamic–pituitary–gonadal axis.

  • 7.
    Kinsman, John
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Angrén, John
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Furberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Mosquera, Paola A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Otero-García, Laura
    Snacken, René
    Derrough, Tarik
    Carrillo Santisteve, Paloma
    Ciotti, Massimo
    Tsolova, Svetla
    Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states2018In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, no 1, article id 528Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: EU Decision 1082/2013/EU on serious cross-border health threats provides a legal basis for collaboration between EU Member States, and between international and European level institutions on preparedness, prevention, and mitigation in the event of a public health emergency. The Decision provides a context for the present study, which aims to identify good practices and lessons learned in preparedness and response to Middle East Respiratory Syndrome (MERS) (in UK, Greece, and Spain) and poliomyelitis (in Poland and Cyprus).

    METHODS: Based on a documentary review, followed by five week-long country visits involving a total of 61 interviews and group discussions with experts from both the health and non-health sectors, this qualitative case study has investigated six issues related to preparedness and response to MERS and poliomyelitis: national plans and overall preparedness capacity; training and exercises; risk communication; linking policy and implementation; interoperability between the health and non-health sectors; and cross-border collaboration.

    RESULTS: Preparedness and response plans for MERS and poliomyelitis were in place in the participating countries, with a high level of technical expertise available to implement them. Nevertheless, formal evaluation of the responses to previous public health emergencies have sometimes been limited, so lessons learned may not be reflected in updated plans, thereby risking mistakes being repeated in future. The nature and extent of inter-sectoral collaboration varied according to the sectors involved, with those sectors that have traditionally had good collaboration (e.g. animal health and food safety), as well as those that have a financial incentive for controlling infectious diseases (e.g. agriculture, tourism, and air travel) seen as most likely to have integrated public health preparedness and response plans. Although the formal protocols for inter-sectoral collaboration were not always up to date, good personal relations were reported within the relevant professional networks, which could be brought into play in the event of a public health emergency. Cross-border collaboration was greatly facilitated if the neighbouring country was a fellow EU Member State.

    CONCLUSIONS: Infectious disease outbreaks remain as an ongoing threat. Efforts are required to ensure that core public health capacities for the full range of preparedness and response activities are sustained.

  • 8.
    Kinsman, John
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stöven, Svenja
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Murillo, Pilar
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Sulzner, Michael
    Good practices and challenges in addressing poliomyelitis and measles in the European Union2018In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 28, no 4, p. 730-734Article in journal (Refereed)
    Abstract [en]

    Background: All European Union (EU) and European Economic Area (EEA) Member States have pledged to ensure political commitment towards sustaining the region's poliomyelitis-free status and eliminating measles. However, there remain significant gaps between policy and practice in many countries. This article reports on an assessment conducted for the European Commission that aimed to support improvements in preparedness and response to poliomyelitis and measles in Europe.

    Methods: A documentary review was complemented by qualitative interviews with professionals working in International and EU agencies, and in at-risk or recently affected EU/EEA Member States (six each for poliomyelitis and measles). Twenty-six interviews were conducted on poliomyelitis and 24 on measles; the data were subjected to thematic analysis. Preliminary findings were then discussed at a Consensus Workshop with 22 of the interviewees and eight other experts.

    Results: Generic or disease-specific plans exist in the participating countries and cross-border communications during outbreaks were generally reported as satisfactory. However, surveillance systems are of uneven quality, and clinical expertise for the two diseases is limited by a lack of experience. Serious breaches of protocol have recently been reported from companies producing poliomyelitis vaccines, and vaccine coverage rates for both diseases were also sub-optimal. A set of suggested good practices to address these and other challenges is presented.

    Conclusions: Poliomyelitis and measles should be brought fully onto the policy agendas of all EU/EEA Member States, and adequate resources provided to address them. Each country must abide by the relevant commitments that they have already made.

  • 9. Nyberg, Ann Göransson
    et al.
    Stricklin, Daniela
    Sellström, Åke
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Mass casualties and health care following the release of toxic chemicals or radioactive material-contribution of modern biotechnology2011In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 8, no 12, p. 4521-4549Article, review/survey (Refereed)
    Abstract [en]

    Catastrophic chemical or radiological events can cause thousands of casualties. Such disasters require triage procedures to identify the development of health consequences requiring medical intervention. Our objective is to analyze recent advancements in biotechnology for triage in mass emergency situations. In addition to identifying persons "at risk" of developing health problems, these technologies can aid in securing the unaffected or "worried well". We also highlight the need for public/private partnerships to engage in some of the underpinning sciences, such as patho-physiological mechanisms of chemical and radiological hazards, and for the necessary investment in the development of rapid assessment tools through identification of biochemical, molecular, and genetic biomarkers to predict health effects. For chemical agents, biomarkers of neurotoxicity, lung damage, and clinical and epidemiological databases are needed to assess acute and chronic effects of exposures. For radiological exposures, development of rapid, sensitive biomarkers using advanced biotechnologies are needed to sort exposed persons at risk of life-threatening effects from persons with long-term risk or no risk. The final implementation of rapid and portable diagnostics tools suitable for emergency care providers to guide triage and medical countermeasures use will need public support, since commercial incentives are lacking.

  • 10.
    Plamboeck, Agneta H.
    et al.
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Stöven, Svenja
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Davidson, Raquel Duarte
    Fykse, Else-Marie
    Griffiths, Mark
    Nieuwenhuizen, Maarten
    Rivier, Cedric
    van der Schans, Marcel
    Laboratory analysis of CBRN-substances: Stakeholder networks as clue to higher CBRN resilience in Europe2016In: TrAC. Trends in analytical chemistry, ISSN 0165-9936, E-ISSN 1879-3142, Vol. 85, no Part B, p. 2-9Article in journal (Refereed)
    Abstract [en]

    The threat of terrorists using CBRN agents continues to pose a risk of mass casualties and severe disruption of societal functions in Europe. Standardisation of crisis management activities is one important step towards effective national and international interoperability and increased resilience. Understanding which CBRN agents are involved in an incident is vital for appropriate response measures. We applied a system's view on the process of CBRN sample analysis and see three discrete applications; Immediate incident response, Forensics, Post incident monitoring. Together with laboratory experts and policy makers from across Europe we identified needs for quality assurance measures in these three areas. Here, we suggest various harmonisation activities that can facilitate interoperability between all stakeholders concerned with CBRN sample analysis. Foremost, we recommend purpose-oriented laboratory networks, but also minimum performance requirements for First Responders' detection and sampling capabilities, best practices for sample transport and documentation.

  • 11.
    Plamboeck, Agneta
    et al.
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Sahovic, Dzenan
    Umeå University, Faculty of Social Sciences, Department of Political Science. Europeiska CBRNE-centret, European CBRNE Center.
    Karlsson Bazarschi, Johanna
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Enhancing First Responder CBRN Capabilities2015In: ABC. Casopis urgentne medicine (Journal of Emergency Medicine), ISSN 1451-1053, Vol. 15, no 2, p. 60-65Article in journal (Other academic)
  • 12.
    Sahovic, Dzenan
    et al.
    Umeå University, Faculty of Social Sciences, Department of Political Science. European CBRNE Center.
    Engberg, Jan
    Umeå University, Faculty of Social Sciences, Department of Political Science.
    Van Hemert, Dianne
    TNO Defence, Safety and Security.
    Nyström, Rebecca
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Lindgren, Karin
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Comparative Mapping of Legal and Political Contexts of Different EU Countries: PRACTICE project deliverable 8.22013Report (Other academic)
  • 13.
    Sellström, Åke
    et al.
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Plamboeck, Agneta
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Sigsworth, Andrew
    Police National CBRN Center .
    Deegan, Andrew
    Police National CBRN Center .
    Brinek, Josef
    SUJCHBO.
    Kralik, Lukas
    SUJCHBO.
    Becker, Anne
    Robert Koch-institute.
    Gebert, Susanne
    Robert Koch-institute.
    Norrhem, Bo
    Lindholmen Science Park.
    Rydberg, Gunilla
    Lindholmen Science Park.
    Sommade, Christian
    HCFDC.
    Dhermain, Joel
    DGA Maitrise NRBC.
    Jacquelard, Christophe
    Cilas.
    Goebel, Johann
    EADS.
    Tunemalm, Anna-Karin
    FOI.
    Bucht, Göran
    FOI.
    Nexon, Elisande
    Foundation Pour la recherche strategique.
    Di Camillo, Federica
    Istituto affari internazionali.
    Miranda, Valérie
    Istituto affari internazionali.
    Riti, Emidio
    Selex Galileo.
    George, Marc
    UCL.
    Menning, Dennis
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Final Report of CBRNEmap: A better preparedness and response for European citizens facing CBRNE Threats2011Report (Other (popular science, discussion, etc.))
    Abstract [en]

    CBRNEmap was a pre-study to the upcoming CBRNE technology demonstrator. Accordingly, considerable efforts were used to describe the feasibility and to sort out a number of basic requirements of the contemplated demonstrator object. This report deals with two areas deemed important when constructing a civilian CBRNE system of systems, its limitations and some suggested specifications: A useful CBRNE system of systems will improve and connect important societal functions vital before, during and after a CBRNE accident and/or attack. CBRNEmap identifies three clusters of activities as the most important when making our society resilient to CBRNE. These are, the cluster of activities making up the response function, the cluster of activities defining the function to protect identified targets and the cluster of societal investments enabling Europe to become more resilient. As examples and as a source of inspiration the three societal functions described above (response, protect and enabling) were used to discuss the CBRNE technology demonstrator. The demonstrator objects were populated by technologies and thereafter discussed with respect to choice of scenarios, choice of parameters to be used for its validation and with respect to its market value. Based on its conclusions, its working process and its interaction with external partners CBRNEmap recommends that:

    The use of Integrated Project Teams will be given priority when evaluating the upcoming demonstrator objects.

    The European Commission does everything possible to ensure that the results of previous “EU project” get integrated into the upcoming demonstrator object.

    Appropriate limitations and projections are made to the CBRNE system of systems perspective, in order to produce a CBRNE demonstrator serving the societal functions responsible or operational active.

    Considerable efforts are given to validating the improvements and/or added value of the demonstrator object.

    The cluster of societal investment we refer to as the enabler is further investigated in a future SSA.

  • 14.
    Stöven, Svenja
    et al.
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Bäcklund, Anna
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Sahovic, Dzenan
    Umeå University, Faculty of Social Sciences, Department of Political Science.
    Ethics Issues Management Workshop: PRACTICE project deliverable 1.32013Report (Other academic)
  • 15.
    Vonkavaara, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Pavel, Shaikh Terkis Islam
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Hölzl, Kathrin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Nordfelth, Roland
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Stöven, Svenja
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Francisella is sensitive to insect antimicrobial peptides2013In: Journal of Innate Immunity, ISSN 1662-811X, E-ISSN 1662-8128, Vol. 5, no 1, p. 50-59Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis causes the zoonotic disease tularemia. Arthropod vectors are important transmission routes for the disease, although it is not known how Francisella survives the efficient arthropod immune response. Here, we used Drosophila melanogaster as a model host for Francisella infections and investigated whether the bacteria are resistant to insect humoral immune responses, in particular to the antimicrobial peptides (AMPs) secreted into the insect hemolymph. Moreover, we asked to which extent such resistance might depend on LPS structure and surface characteristics of the bacteria. We analyzed F. novicida mutant strains in genes, directly or indirectly involved in specific steps of LPS biosynthesis, for virulence in wildtype and Relish E20 immune deficient flies, and tested selected mutants for sensitivity to AMPs in vitro. We demonstrate that Francisella is sensitive to specific fly AMPs, i.e. Attacin, Cecropin, Drosocin and Drosomycin. Furthermore, six bacterial genes, kpsF, manB, lpxF, slt, tolA and pal, were found to be required for resistance to Relish-dependent immune responses, illustrating the importance of structural details of Francisella lipid A and Kdo core for interactions with AMPs. Interestingly, a more negative surface charge and lack of O-antigen did not render mutant bacteria more sensitive to cationic AMPs and attenuated virulence in flies.

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