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ComBact SIGNED
How complement molecules kill bacteria
Total Cost €
0EC-Contrib. €
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Explore the words cloud of the ComBact project. It provides you a very rough idea of what is the project "ComBact" about.
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Project "ComBact" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITAIR MEDISCH CENTRUM UTRECHT
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Project website | http://www.evasionutrecht.nl/staff/suzan-rooijakkers/ |
| Total cost | 1˙497˙290 € |
| EC max contribution | 1˙497˙290 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-03-01 to 2020-02-29 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITAIR MEDISCH CENTRUM UTRECHT | NL (UTRECHT) | coordinator | 1˙497˙290.00 |
Map
Project objective
This proposal aims to provide insight into how bacteria are killed by the complement system, an important part of the host immune response against bacterial infections. Complement is a large protein network in plasma that labels bacteria for phagocytosis and directly kills them via the formation of a pore-forming complex (Membrane Attack Complex (MAC)). Currently we do not understand how complement activation results in bacterial killing. This knowledge gap is mainly caused by the lack of tools to study the enzymes that trigger MAC formation: the C5 convertases.
In my lab, we recently established a novel assay system for C5 convertases that allows us for the first time to study these enzymes under purified conditions. This model, combined with my expertise in microbiology, places my lab in a unique position to understand C5 convertase biology (Aim 1), determine the enzyme's role in MAC functioning (Aim 2) and elucidate how the MAC kills bacteria (Aim 3). Thus, I aim to provide insight into the molecular events necessary for bacterial killing by the complement system.
I will use biochemical, structural and microbiological approaches to elucidate the precise molecular arrangement of C5 convertases in vitro and on bacterial cells. I will generate unique tools to study how C5 convertases regulate MAC insertion into bacterial membranes. Finally, I will engineer fluorescent bacteria and labeled complement proteins to perform advanced microscopy analyses of how MAC kills bacteria.
These insights will lead to fundamental knowledge about the functioning of complement and will create new avenues for blocking the undesired complement activation during systemic infections and acute inflammatory processes. Furthermore this knowledge will improve desired complement activation by therapeutic antibodies and vaccination strategies in infectious diseases. Finally, this work opens up new possibilities to understand how both humans and bacteria regulate complement.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Dennis J Doorduijn, Bart W Bardoel, Dani AC Heesterbeek, Maartje Ruyken, Georgina Benn, Edward S Parsons, Bart Hoogenboom, Suzan HM Rooijakkers Bacterial killing by complement requires direct anchoring of Membrane Attack Complex precursor C5b-7 published pages: , ISSN: , DOI: 10.1101/2019.12.17.877639 |
Review Commons | 2020-04-24 |
| 2020 |
Dani A. C. Heesterbeek, Remy M. Muts, Vincent P. van Hensbergen, Pieter de Saint Aulaire, Tom Wennekes, Bart W. Bardoel, Nina M. van Sorge, Suzan H.M. Rooijakkers Outer membrane permeabilization by the membrane attack complex sensitizes Gram-negative bacteria to antimicrobial proteins in serum and phagocytes published pages: , ISSN: , DOI: 10.1101/2020.01.28.923243 |
Review Commons | 2020-04-24 |
| 2018 |
Dani Heesterbeek Type: Poster presentation – selected abstractDescription: Poster presentation at the Dutch Complement Symposium 2018Title: “Bacterial killing by complement requires membrane attack complex formation via surface-bound C5-convertases†published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2018 |
Seline Zwarthoff Type: Poster presentationDescription: Presentation at Keystone Symposia, Antibodies as Drugs: Translating Molecules into Treatments (C1), Whistler, CanadaTitle: Proteases C1r and C1s regulate binding of C1q to certain human IgG subclasses published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2018 |
Dani Heesterbeek Type: Oral presentationDescription: Presentation at the Science for life symposium, Utrecht, 2018Title: “The role of C5 convertases in MAC dependent killing of Gram-negative bacteria†published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2019 |
Dennis J Doorduijn Oral presentationDescription: Presentation at the Scientific Spring Meeting KNVM & NVMM 2019Title: \'Molecular insights into the killing of E. coli by Membrane Attack Complex pores’ published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2019 |
Seline Zwarthoff Type: Oral presentationDescription: Presentation at KNVM & NVMM Scientific Spring meeting 2019, ArnhemTitle: Proteases C1r and C1s affect binding of C1q to certain human IgG subclasses published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2019 |
Dani Heesterbeek Type: Oral presentation – for kiem award Description: Presentation at the Scientific Spring Meeting of the Dutch Society of Microbiology (NVMM & KNVM)Title: “Bacterial killing by complement requires membrane attack complex formation via surface-bound C5-convertases†published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2018 |
Bart Bardoel Type: Oral presentationDescription: Prato pores conference 2018’Title: “The human complement system sensitizes Gram-negative bacteria for Gram-positive-specific antibiotics via pore formation in the outer membrane†published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2019 |
Seline Abigaïl Zwarthoff How antibodies drive complement activation Paving the road towards effective therapeutics published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2018 |
Seline Zwarthoff Type: Poster presentationDescription: Presentation at Dutch Complement Symposium, Nunspeet, The NetherlandsTitle: Proteases C1r and C1s affect binding of C1q to certain human IgG subclasses published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2019 |
Dani Heesterbeek Type: Poster presentation – selected abstractDescription: Poster presentation at the EMBL conference: new concepts and approaches in microbiologyTitle: “Generation of a fluorescent reporter system in E. coli to study bacterial membrane damage by the immune system†published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2018 |
Seline Zwarthoff Type: Poster presentationDescription: Presentation at Science for Life Conference, Utrecht, the Netherlands Title: Proteases C1r and C1s affect binding of C1q to certain human IgG subclasses published pages: , ISSN: , DOI: |
2019-10-29 | |
| 2018 |
Fernanda L. Paganelli, Helen L. Leavis, Samantha He, Nina M. van Sorge, Christine Payré, Gérard Lambeau, Rob J. L. Willems, Suzan H. M. Rooijakkers Group IIA-Secreted Phospholipase A 2 in Human Serum Kills Commensal but Not Clinical Enterococcus faecium Isolates published pages: , ISSN: 0019-9567, DOI: 10.1128/iai.00180-18 |
Infection and Immunity 86/8 | 2019-10-10 |
| 2017 |
DAC Heesterbeek oral presentation: The role of convertases in MACdependent killing of bacteria published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2019 |
Dani A. C. Heesterbeek how complement kills bacteria: a pore way to die published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2019 |
S Zwarthoff oral presentation: Proteases C1r and C1s affect binding of C1q to certain human IgG subclasses published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2019 |
D. A. C. Heesterbeek, N. I. Martin, A. Velthuizen, M. Duijst, M. Ruyken, R. Wubbolts, S. H. M. Rooijakkers, B. W. Bardoel Complement-dependent outer membrane perturbation sensitizes Gram-negative bacteria to Gram-positive specific antibiotics published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-38577-9 |
Scientific Reports 9/1 | 2019-10-10 |
| 2018 |
Dani A.C. Heesterbeek, Mathieu L. Angelier, Richard A. Harrison, Suzan H.M. Rooijakkers Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications published pages: 455-464, ISSN: 1662-811X, DOI: 10.1159/000491439 |
Journal of Innate Immunity 10/5-6 | 2019-10-10 |
| 2018 |
Nienke W. M. de Jong, Manouk Vrieling, Brandon L. Garcia, Gerrit Koop, Matt Brettmann, Piet C. Aerts, Maartje Ruyken, Jos A. G. van Strijp, Mark Holmes, Ewan M. Harrison, Brian V. Geisbrecht, Suzan H. M. Rooijakkers Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains published pages: 4468-4477, ISSN: 0021-9258, DOI: 10.1074/jbc.RA117.000599 |
Journal of Biological Chemistry 293/12 | 2019-10-10 |
| 2018 |
Seline A. Zwarthoff, Evelien T. M. Berends, Sanne Mol, Maartje Ruyken, Piet C. Aerts, Mihály Józsi, Carla J. C. de Haas, Suzan H. M. Rooijakkers, Ronald D. Gorham Functional Characterization of Alternative and Classical Pathway C3/C5 Convertase Activity and Inhibition Using Purified Models published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.01691 |
Frontiers in Immunology 9 | 2019-10-10 |
| 2019 |
Dennis J. Doorduijn, Suzan H. M. Rooijakkers, Dani A. C. Heesterbeek How the Membrane Attack Complex Damages the Bacterial Cell Envelope and Kills Gramâ€Negative Bacteria published pages: 1900074, ISSN: 0265-9247, DOI: 10.1002/bies.201900074 |
BioEssays 41/10 | 2019-10-10 |
| 2019 |
D J Doorduijn Bacterial killing by MAC pores requires immediate assembly of C5b-7 published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2017 |
SHM Rooijakkers invited lecture: Complement as a recognition molecule system published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2017 |
Bart Bardoel oral presentation: Complement sensitizes Gram-negativebacteria for Gram-positive-specific antibiotics published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2018 |
Bart Bardoel (replacing Suzan Rooijakkers) invited lecture: Molecular insights into complement-mediated killing of Gram-negative bacteria published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2019 |
DAC Heesterbeek oral presentation: Disruption of Gram-negative bacteria by human serum requires complement and lysozyme published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2018 |
Dennis Doorduijn oral presentation: Surface-bound enzymes facilitate pore formation by the Membrane Attack Complex to efficiently kill Gram-negative bacteria published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2019 |
Heesterbeek, D. A.; Bardoel, B. W.; Parsons, E. S.; Bennett, I.; Ruyken, M.; Doorduijn, D. J.; Gorham, R. D.; Berends, E. T.; Pyne, A. L.; Hoogenboom, B. W.; Rooijakkers, S. H. Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases published pages: , ISSN: 1460-2075, DOI: 10.15252/embj.201899852 |
EMBO Journal , Article e99852. (2019) (In press). 1 | 2019-10-10 |
| 2019 |
S.H.M. Rooijakkers Invited lecture: Antibody-mediated killing of bacteria by complement published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2018 |
SHM Rooijakkers invited lecture: Antibodyâ€Mediated Killing ofBacteria by Complement published pages: , ISSN: , DOI: |
2019-10-10 | |
| 2017 |
Seline Zwarthoff \"Oral presentation: \"\"Defining the molecular interplay between antibodies and complement in bacterial infections\"\"\" published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Daphne A.C. Stapels, Jordan L. Woehl, Fin J. Milder, Angelino T. Tromp, Aernoud A. van Batenburg, Wilco C. de Graaf, Samuel C. Broll, Natalie M. White, Suzan H.M. Rooijakkers, Brian V. Geisbrecht Evidence for Multiple Modes of Neutrophil Serine Protease Recognition by the EAP Family of Staphylococcal Innate Immune Evasion Proteins published pages: , ISSN: 0961-8368, DOI: 10.1002/pro.3342 |
Protein Science | 2019-05-29 |
| 2016 |
Fernanda L. Paganelli Oral presentationTitle: Genome-wide screening identifies PTS permease BepA to be involved in Enterococcus faecium endocarditis and biofilm formation. published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Dani Heesterbeek Oral presentation: The role of C5 convertases in MAC-dependent killing of Gram-negative bacteria published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Fernanda L. Paganelli Oral presentation: YajC Promotes Enterococcus faecium and Staphylococcus aureus Biofilm Formation by Retaining Intracellular Protein at the Bacterial Surface published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Brandon L. Garcia, Seline A. Zwarthoff, Suzan H. M. Rooijakkers, Brian V. Geisbrecht Novel Evasion Mechanisms of the Classical Complement Pathway published pages: 2051-2060, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1600863 |
The Journal of Immunology 197/6 | 2019-05-29 |
| 2016 |
Suzan Rooijakkers \"Invited lecture: \"\"How the human complement system kills bacteria\"\".\" published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Ron D Gorham Jr Poster presentation: Functional characterization of alternative pathway C3 and C5 convertase inhibitors published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Dennis Doorduijn Poster presentation: Creating model systems to study molecular mechanisms of C5-convertase-induced Membrane Attack Complex assembly published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Bart Bardoel Poster presentation: Complement sensitizes Gram-negative bacteria for gram-positive specific antibiotics published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Dani Heesterbeek Oral presentation: C5 convertases in MAC-dependent killing of Gram-negative bacteria published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Seline Zwarthoff Oral presentation: Mimicking classical complement activation in purified model systems published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Suzan Rooijakkers \"Invited lecture: \"\"Complement Activation as a target for combating infections\"\"\" published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2015 |
Bart Bardoel Poster presentation published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Dennis Doorduijn Poster presentation: A liposome model to study structural and functional aspects of the Membrane Attack Complex in complex with a C5-convertase published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Dani Heesterbeek Oral presentation: C5 convertases drive MAC-dependent killing of Gram-negative bacteria published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2015 |
Suzan Rooijakkers Invited lecture: How Staphylococcus aureus escapes the immune system. published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2015 |
Daphne Stapels Immune-evasion of Staphylococcus aureus via its extracellular adherence proteins published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Suzan Rooijakkers \"Keynote lecture at the Florey symposium for host-pathogen interactions. \"\"Molecular interplay between complement and bacteria\"\".\" published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Suzan Rooijakkers \"Invited lecture: \"\"Enhancing complement activation on bacteria\"\".\" published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Elise S. Hovingh, Bryan van den Broek, Betsy Kuipers, Elena Pinelli, Suzan H. M. Rooijakkers, Ilse Jongerius Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface published pages: e1006531, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006531 |
PLOS Pathogens 13/7 | 2019-05-29 |
| 2016 |
Ron D Gorham Jr Poster presentation: Elucidating the molecular mechanisms of complement-mediated neutrophil phagocytosis published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Seline Zwarthoff Poster presentation: Defining the molecular interplay between antibodies and complement in bacterial infections published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Seline Zwarthoff Poster presentation: Mimicking classical complement activation in purified model systems published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2015 |
Evelien Berends Molecular interplay between bacteria and the terminal complement pathway published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Dani Heesterbeek Oral presentation: Role of C5 convertases in MAC-dependent killing of Gram-negative bacteria published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2015 |
Suzan Rooijakkers \"\"\"Complement activation on bacteria\"\"\" published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Suzan Rooijakkers Keynote lecture at the Dublin Academy for Pathogenomics and Infection Biology. published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2015 |
Ron D Gorham Jr Poster presentation: Discovery of small molecules for fluorescent detection of complement activation product C3d published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Ron D Gorham Jr Oral presentation: Functional characterization of alternative pathway C3 and C5 convertase inhibitors published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Ron D Gorham Jr Poster presentation: molecular mechanisms of complement-mediated neutrophil phagocytosis published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2016 |
Bart Bardoel Oral presentation: “Genome-wide CRISPR screen reveals novel host factors required for Staphylococcus aureus α-hemolysin-mediated toxicity†published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Bart Bardoel Oral presentation: “Complement sensitizes Gram-negative bacteria for “Gram-positive specific†antibiotics†published pages: , ISSN: , DOI: |
2019-05-29 | |
| 2017 |
Kaila M. Bennett, Suzan H. M. Rooijakkers, Ronald D. Gorham Let’s Tie the Knot: Marriage of Complement and Adaptive Immunity in Pathogen Evasion, for Better or Worse published pages: , ISSN: 1664-302X, DOI: 10.3389/fmicb.2017.00089 |
Frontiers in Microbiology 8 | 2019-05-27 |
| 2016 |
Kuipers, A Mechanisms to suppress or enhance phagocytosis of staphylococci published pages: , ISSN: , DOI: |
4 | 2019-05-27 |
| 2016 |
Dennis J. Doorduijn, Suzan H.M. Rooijakkers, Willem van Schaik, Bart W. Bardoel Complement resistance mechanisms of Klebsiella pneumoniae published pages: 1102-1109, ISSN: 0171-2985, DOI: 10.1016/j.imbio.2016.06.014 |
Immunobiology 221/10 | 2019-05-27 |
| 2015 |
Evelien T. M. Berends, Ronald D. Gorham, Maartje Ruyken, Jasper A. Soppe, Hatice Orhan, Piet C. Aerts, Carla J. C. de Haas, Piet Gros, Suzan H. M. Rooijakkers Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-015-0203-8 |
BMC Biology 13/1 | 2019-05-27 |
| 2016 |
Annemarie Kuipers, Daphne A. C. Stapels, Maartje Ruyken, Lleroy T. Weerwind, Suzan H. M. Rooijakkers, Jean C. Lee, Kok P. M. van Kessel, Ya-Ping Ko The Staphylococcus aureus polysaccharide capsule and Efb-dependent fibrinogen shield act in concert to protect against phagocytosis published pages: 1185-1194, ISSN: 1350-0872, DOI: 10.1099/mic.0.000293 |
Microbiology 162/7 | 2019-05-27 |
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