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{"title"=>"Conserved patterns of microbial immune escape: Pathogenic microbes of diverse origin target the human terminal complement inhibitor vitronectin via a single common motif", "type"=>"journal", "authors"=>[{"first_name"=>"Teresia", "last_name"=>"Hallström", "scopus_author_id"=>"16303468000"}, {"first_name"=>"Birendra", "last_name"=>"Singh", "scopus_author_id"=>"55986697200"}, {"first_name"=>"Peter", "last_name"=>"Kraiczy", "scopus_author_id"=>"6701585923"}, {"first_name"=>"Sven", "last_name"=>"Hammerschmidt", "scopus_author_id"=>"56091235400"}, {"first_name"=>"Christine", "last_name"=>"Skerka", "scopus_author_id"=>"7003585724"}, {"first_name"=>"Peter F.", "last_name"=>"Zipfel", "scopus_author_id"=>"7005356246"}, {"first_name"=>"Kristian", "last_name"=>"Riesbeck", "scopus_author_id"=>"7003411010"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84959232606", "pui"=>"608240373", "doi"=>"10.1371/journal.pone.0147709", "sgr"=>"84959232606", "pmid"=>"26808444"}, "id"=>"efa1d889-25c6-3218-a5bb-66187672cb6f", "abstract"=>"Pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. Here we show that different human pathogens including Gram-negative and Gram-positive bacteria, as well as the fungal pathogen Candida albicans, acquire the human terminal complement regulator vitronectin to their surface. By using truncated vitronectin fragments we found that all analyzed microbial pathogens (n = 13) bound human vitronectin via the same C-terminal heparin-binding domain (amino acids 352-374). This specific interaction leaves the terminal complement complex (TCC) regulatory region of vitronectin accessible, allowing inhibition of C5b-7 membrane insertion and C9 polymerization. Vitronectin complexed with the various microbes and corresponding proteins was thus functionally active and inhibited complement-mediated C5b-9 deposition. Taken together, diverse microbial pathogens expressing different structurally unrelated vitronectin-binding molecules interact with host vitronectin via the same conserved region to allow versatile control of the host innate immune response.", "link"=>"http://www.mendeley.com/research/conserved-patterns-microbial-immune-escape-pathogenic-microbes-diverse-origin-target-human-terminal", "reader_count"=>20, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Bosnia and Herzegovina"=>1}, "group_count"=>0}

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• http://doi.org/10.1183/16000617.0018-2018
• http://doi.org/10.1038/srep24391
• http://doi.org/10.1016/j.micpath.2020.104111
• http://doi.org/10.1371/journal.pone.0157413
• http://doi.org/10.1016/j.ijmm.2016.09.001
• http://doi.org/10.1007/s10157-017-1405-x
• http://doi.org/10.1016/j.fsi.2017.03.055
• http://doi.org/10.3389/fmicb.2016.02004
• http://doi.org/10.3389/fcimb.2017.00061
• http://doi.org/10.3389/fmicb.2018.01559
• http://doi.org/10.1093/femspd/ftx017
• http://doi.org/10.1038/s41598-018-23194-9
• http://doi.org/10.1183/16000617.0040-2018
• http://doi.org/10.1016/j.ecoenv.2018.04.021
• http://doi.org/10.1111/cmi.12732
• http://doi.org/10.3390/ijms20092345
• http://doi.org/10.1002/1873-3468.13758
• http://doi.org/10.1111/mmi.14084

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/2632957"], "description"=>"<p>A series of Gram-negative and Gram-positive bacterial species and <i>Candida albicans</i> were grown overnight and incubated with [¹²⁵I]-labeled vitronectin purified from plasma (A) or recombinant vitronectin^80-396 (B). After washing, bound vitronectin was determined by liquid scintillation counting. The mean values of three experiments are shown. In C, the relative binding of [¹²⁵I]-labeled vitronectin to selected microbes are shown. The mean values of three experiments are shown with error bars indicating standard deviations (SD).</p>", "links"=>[], "tags"=>["host microbes", "C 9 polymerization", "complement evasion strategies", "Microbial Immune Escape", "C 5b membrane insertion", "Human Terminal Complement Inhibitor Vitronectin", "Diverse Origin Target", "tcc", "Single Common Motif Pathogenicity", "Vitronectin complexed", "Conserved Patterns", "pathogen Candida albicans", "host vitronectin", "vitronectin fragments", "region", "terminal complement", "Pathogenic Microbes", "terminal complement regulator vitronectin"], "article_id"=>1641368, "categories"=>["Biological Sciences"], "users"=>["Teresia Hallström", "Birendra Singh", "Peter Kraiczy", "Sven Hammerschmidt", "Christine Skerka", "Peter F. Zipfel", "Kristian Riesbeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0147709.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pathogenic_microbes_bind_the_terminal_complement_pathway_inhibitor_vitronectin_/1641368", "title"=>"Pathogenic microbes bind the terminal complement pathway inhibitor vitronectin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:40:47"}
• {"files"=>["https://ndownloader.figshare.com/files/2632958"], "description"=>"<p>Heparin and NaCl inhibited the binding of [¹²⁵I]-labeled vitronectin to the microbial pathogens. The microbial pathogens were incubated with [¹²⁵I]-labeled vitronectin and 10 μM heparin (A) or 1 M NaCl (B), followed by washing and determination of radioactivity associated with the pellet. The vitronectin binding of each microbe in the absence of competitor was defined as 100%. The mean values of three experiments are shown with error bars indicating SD. Statistical significance of differences was estimated using Student’s <i>t</i> test. **, <i>p</i>≤ 0.01; ***, <i>p</i>≤ 0.001.</p>", "links"=>[], "tags"=>["host microbes", "C 9 polymerization", "complement evasion strategies", "Microbial Immune Escape", "C 5b membrane insertion", "Human Terminal Complement Inhibitor Vitronectin", "Diverse Origin Target", "tcc", "Single Common Motif Pathogenicity", "Vitronectin complexed", "Conserved Patterns", "pathogen Candida albicans", "host vitronectin", "vitronectin fragments", "region", "terminal complement", "Pathogenic Microbes", "terminal complement regulator vitronectin"], "article_id"=>1641369, "categories"=>["Biological Sciences"], "users"=>["Teresia Hallström", "Birendra Singh", "Peter Kraiczy", "Sven Hammerschmidt", "Christine Skerka", "Peter F. Zipfel", "Kristian Riesbeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0147709.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_binding_of_vitronectin_is_inhibited_by_heparin_and_high_ionic_strength_/1641369", "title"=>"The binding of vitronectin is inhibited by heparin and high ionic strength.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:40:48"}
• {"files"=>["https://ndownloader.figshare.com/files/2632960"], "description"=>"<p>(A) Schematic representation of the different truncated vitronectin (Vn) fragments and deletion mutants used for analysis of vitronectin binding. (B) Eight different microbes, including Gram-negative and Gram-positive bacteria and <i>C</i>. <i>albicans</i> were incubated with truncated recombinant vitronectin fragments and three vitronectin deletion mutants. NHS was run in parallel as a positive control. Microbes were washed and total proteins were separated by SDS-PAGE gels, transferred to a membrane and bound vitronectin fragments were detected using an anti- vitronectin polyclonal antiserum. One representative experiment of three independent ones performed is shown. (C) Microbes were immobilized on microtiter plates and incubated with vitronectin fragments including deletion mutants. Bound fragments were detected with rabbit anti-vitronectin pAb and secondary HRP-conjugated goat anti-rabbit pAb. The mean values of three experiments are shown with error bars indicating SD. Statistical significance of differences was estimated using Student’s <i>t</i> test. *, <i>p</i>≤ 0.05; **, <i>p</i>≤ 0.01; ***, <i>p</i>≤ 0.001.</p>", "links"=>[], "tags"=>["host microbes", "C 9 polymerization", "complement evasion strategies", "Microbial Immune Escape", "C 5b membrane insertion", "Human Terminal Complement Inhibitor Vitronectin", "Diverse Origin Target", "tcc", "Single Common Motif Pathogenicity", "Vitronectin complexed", "Conserved Patterns", "pathogen Candida albicans", "host vitronectin", "vitronectin fragments", "region", "terminal complement", "Pathogenic Microbes", "terminal complement regulator vitronectin"], "article_id"=>1641371, "categories"=>["Biological Sciences"], "users"=>["Teresia Hallström", "Birendra Singh", "Peter Kraiczy", "Sven Hammerschmidt", "Christine Skerka", "Peter F. Zipfel", "Kristian Riesbeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0147709.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_microbial_binding_site_is_located_within_the_third_HBD_/1641371", "title"=>"The microbial binding site is located within the third HBD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:40:48"}
• {"files"=>["https://ndownloader.figshare.com/files/2632962"], "description"=>"<p>(A) Recombinant Hsf (Hib), PE (NTHi), UspA2H (<i>M</i>. <i>catarrhalis</i>), Msf (<i>N</i>. <i>menigitidis</i>), Lpd (<i>P</i>. <i>aeruginosa</i>), PspC (<i>S</i>. <i>pneumoniae</i>), Scl1 (<i>S</i>. <i>pyogenes</i>) and Gpm1 (<i>C</i>. <i>albicans</i>) (5 μg/ml) were immobilized in microtiter plates and incubated with vitronectin (5 μg/ml). (B) Microbial proteins were immobilized on microtiter plates and incubated with recombinant vitronectin fragments and deletion mutants. The diamonds represent the microbial proteins tested. In (A) and (B), bound vitronectin fragments and deletion mutants were detected with a vitronectin reacting polyclonal antiserum and HRP-conjugated anti-rabbit pAb. The mean values of three experiments are shown with error bars indicating SD. Binding to vitronectin was statistically significant (<i>p</i>≤ 0.001) for all microbial proteins.</p>", "links"=>[], "tags"=>["host microbes", "C 9 polymerization", "complement evasion strategies", "Microbial Immune Escape", "C 5b membrane insertion", "Human Terminal Complement Inhibitor Vitronectin", "Diverse Origin Target", "tcc", "Single Common Motif Pathogenicity", "Vitronectin complexed", "Conserved Patterns", "pathogen Candida albicans", "host vitronectin", "vitronectin fragments", "region", "terminal complement", "Pathogenic Microbes", "terminal complement regulator vitronectin"], "article_id"=>1641373, "categories"=>["Biological Sciences"], "users"=>["Teresia Hallström", "Birendra Singh", "Peter Kraiczy", "Sven Hammerschmidt", "Christine Skerka", "Peter F. Zipfel", "Kristian Riesbeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0147709.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_All_microbial_proteins_use_a_common_binding_site_within_the_vitronectin_molecule_/1641373", "title"=>"All microbial proteins use a common binding site within the vitronectin molecule.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:40:53"}
• {"files"=>["https://ndownloader.figshare.com/files/2632963"], "description"=>"<p>Vitronectin (25–50 μg/ml) was bound to Hib (<i>A</i>), NTHi (<i>B</i>), <i>M</i>. <i>catarrhalis</i> (<i>C</i>) or <i>P</i>. <i>aeruginosa</i> (<i>D</i>), and after extensive washing C5b-6 and C7 were added. After incubation for 10 min, C8 and C9 were added, and thereafter C5b-9 deposition on the microbial surface was detected with a mouse anti-C5b-9 mAb and Alexa 647-conjugated anti-mouse pAb by flow cytometry. E, vitronectin (50 μg/ml) was bound to immobilized proteins, and after extensive washing C5b-6 and C7 were added. After 10 min incubation, C8 and C9 were added, and C5b-9 deposition was detected with a mouse anti-C5b-9 mAb and an HRP-conjugated anti-mouse polyclonal antiserum. The mean values from three independent experiments are shown with error bars indicating SD. **, <i>p</i> ≤ 0.01; ***, <i>p</i> ≤ 0.001.</p>", "links"=>[], "tags"=>["host microbes", "C 9 polymerization", "complement evasion strategies", "Microbial Immune Escape", "C 5b membrane insertion", "Human Terminal Complement Inhibitor Vitronectin", "Diverse Origin Target", "tcc", "Single Common Motif Pathogenicity", "Vitronectin complexed", "Conserved Patterns", "pathogen Candida albicans", "host vitronectin", "vitronectin fragments", "region", "terminal complement", "Pathogenic Microbes", "terminal complement regulator vitronectin"], "article_id"=>1641374, "categories"=>["Biological Sciences"], "users"=>["Teresia Hallström", "Birendra Singh", "Peter Kraiczy", "Sven Hammerschmidt", "Christine Skerka", "Peter F. Zipfel", "Kristian Riesbeck"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0147709.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vitronectin_bound_to_intact_bacteria_inhibits_C5b_9_deposition_/1641374", "title"=>"Vitronectin bound to intact bacteria inhibits C5b-9 deposition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-28 12:40:52"}

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• {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
• {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2020", "month"=>"3"}
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• {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}

F1000Prime