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Sökning: WFRF:(Morré Servaas A) > (2015-2019)

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1.
  • Van Den Heuvel, Lambertus, et al. (författare)
  • Genetic predisposition to infection in a case of atypical hemolytic uremic syndrome
  • 2018
  • Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 63:1, s. 93-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Most cases of hemolytic uremic syndrome (HUS) are caused by infection with enterohemorrhagic Escherichia coli (EHEC). Genetic defects causing uncontrolled complement activation are associated with the more severe atypical HUS (aHUS). Non-EHEC infections can trigger the disease, however, complement defects predisposing to such infections have not yet been studied. We describe a 2-month-old patient infected with different Gram-negative bacterial species resulting in aHUS. Serum analysis revealed slow complement activation kinetics. Rare variant R229C was found in complement inhibitor vitronectin. Recombinant mutated vitronectin showed enhanced complement inhibition in vitro and may have been a predisposing factor for infection. Our work indicates that genetic changes in aHUS can not only result in uncontrolled complement activation but also increase vulnerability to infections contributing to aHUS.
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2.
  • Hadfield, James, et al. (författare)
  • Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion
  • 2017
  • Ingår i: Genome Research. - : Cold Spring Harbor Laboratory Press. - 1088-9051 .- 1549-5469. ; 27:7, s. 1220-1229
  • Tidskriftsartikel (refereegranskat)abstract
    • Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.
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