Combating Mycobacterium tuberculosis using electron microscopy
Mycobacterium tuberculosis is the deadliest bacterium in the history of mankind. Despite the development of antibiotics and vaccines, this aerosol transmitted human pathogen still causes 1.4 million deaths per year. Understanding the biology of these bacteria is even more relevant since the spread of multi and even total drug resistant strains. In the Van der Wel group, we are focusing on 3 aspects of the biology, mostly driven by high resolution analysis of these bacteria. By visualizing the bacteria in cells, but also in cultures we have a described a novel pathogenicity factor, discovered the capsular layer is extremely labile and demonstrated a novel strategy to kill these bacteria.
Contact: N. van der Wel (n.n.vanderwel@amsterdamumc.nl)
1. Subcellular trafficking of mycobacteria; a pathogenicity factor
Understanding the virulence mechanisms of Mycobacteria is essential for vaccine development. We have demonstrated that M. tuberculosis is able to translocate from the phagolysosomal compartment into the cytosol of host cells (van der Wel et al.,2007), which completely shifted the paradigm of the known virulence mechanisms of M. tuberculosis. The vaccine currently used to prevent M. tuberculosis infections is M. bovis BCG. This live vaccine was developed almost 1 century ago and has not been improved ever since. We collaborate with several groups worldwide (Amsterdam VU, Germany, France, Spain, Swiss, USA, South Africa) to improve this vaccine and understand the biology of tuberculosis infection (figure 1). The rationale behind the improving the vaccines lies in the analysis of the behavior of the bacteria in host cells. The subcellular localization within cultured cells is different for pathogenic bacteria such as M. tuberculosis compared to the nonpathogenic vaccines BCG (figure 2) and is subject of our ongoing research. We investigate different mutants for the subcellular trafficking in host cells and also the behavior of these bacteria in vivo using fluorescence and electron microscopy and Combined Light and Electron Microscopy (figure 3).
2. High resolution analysis of the lipid-rich capsular layer in Mycobacteria
The outermost layer of mycobacteria consists of a labile structure that contains several secreted products, which are involved in the immune responses of pathogenic bacteria (figure 4). In collaboration with Wilbert Bitters group (VUmc), we have investigated the capsular stability and demonstrated that the ESX5 secretion system is crucial. Now we are analyzing the regeneration of the capsular layer using cryo-EM and immunolabellings. The project serves both fundamental innovative research and has a clear application in the vaccine manufacturing as the capsular layer is the first encounter of the vaccine BCG with the host.
3. Condensation of DNA as a generic stress response in Mycobacterium tuberculosis
Multidrug-resistant tuberculosis is a serious threat to public health worldwide. Even in Europe, about 10% of the Mycobacterium tuberculosis cases are confronted with resistance. Recently we have discovered that M. tuberculosis condenses its DNA in response to antibiotic stress (Scutigliani et al., 2018 see publications). Condensation is visualized using high resolution fluorescence and electron microscopy (figure 5). DNA-condensation of is an established mechanism to survive antibiotic stress, and in developing multidrug resistance. We have demonstrated that condensation appears rapidly after antibiotic stress and does not affect the viability of M. tuberculosis (figure 6). Interestingly patient derived, multidrug-resistant M. tuberculosis strains are more capable of condensing their DNA than drug-susceptible strains. These results imply that by condensing their DNA, mycobacteria can avoid the effects of antibiotics, which facilitates resistance development. Our study provides the first principal evidence that DNA-condensation is a reversible, generic stress response of viable M. tuberculosis, and we are currently screening for new therapeutic approaches to manipulate the DNA condensation and reduce survival specifically of latent and multidrug resistant TB.
4. Electron microscopy
At the Core facility Cellular Imaging, several different microscopy techniques are made available for the AMC-staff, and affiliated researchers (www.cellularimaging.nl). Since March 2014 Dr. Nicole van der Wel was appointed head Electron Microscopy. With a group of 4 research technicians (Daisy Picavet, Henk van der Veen, Edwin Scholl and Anita Grootemaat) and 2 pathology technicians (Per Larsen and Jeannette Pankras) we assist researchers from the AMC and partners with performing Electron Microscopy. We give advice on the techniques needed, support performing and interpretation of the experiments.
In addition to the AMC work, we opened November 2015 the Electron Microscopy Centre Amsterdam (EMCA) (www.cellularimaging.nl/electron-microscopy/). The EMCA is a collaboration between several Amsterdam life science research institutes, including the Vumc, AMC, NKI, ACTA and NIN, and is housed at Core facility Cellular Imaging within the department of Medical Biology at the AMC. At the EMCA the operators and researchers from the different universities and institutes work on the various TEM and SEM microscopes and have shared work-discussions. As such we collaborate with most Amsterdam and various (inter)national research groups and have created an EM knowledge centre in Amsterdam. We have long standing expertise in transmission electron microscopy (TEM), scanning electron microscopy (SEM), but also apply new developments such as combined light electron microscopy (CLEM), tomography, immunoEM, and Cryo-EM.
Figure 1. Schematic representation of the subcellular localization of pathogenic mycobacteria (in red) and the vaccine strain BCG and mutant BCG, designed to release its antigens into the cytosol.
Figure 2. Electron microscopy of 60 nm thin sections of infected dendritic cells. Localization of pathogenic mycobacterium (A) M. tuberculosis (M.tub) differs from the nonpathogenic (B) M. bovis BCG (BCG) as pathogenic mycobacteria escape from the phagolysosomes (blue). Immunogold labelling for LAMP1 is present on lysosomes, and BCG containing phagolysosomes. Bottom images are a schematic cartoon of the lysosomes color coded in blue and the bacteria in red.
Figure 3. In vivo localization of pathogenic mycobacteria imaged with Transmission Electron Microscopy (TEM), Fluorescence Microscopy with nuclei in blue, vessel in red and mycobacteria in green.
Figure 4. Cryo-EM of intact mycobacteria cultured with (left panel) and without detergent (right panel). Bacteria clump without detergent but at high magnification, the capsular layer can be visualized.
Figure 5. Combined Light and Electron Microscopy of mycobacteria stained for lipids (red) and DNA (green). Mycobacteria can condense their DNA/nucleoid when viable.
Figure 6. Fluorescent microscopy of bacteria with (top) and without (bottom) antibiotics stained for DNA (blue) and lipids (red). After treatment with antibiotics, the bacteria appear to have a single clump of DNA while in the untreated a chain of smaller structure form the nucleoid.
Nicole van der Wel, M3-133, 64757, N.N.vanderwel@amsterdamumc.nl
Head Electron Microscopy
Irene Schimmel, M3-132, 64708, i.m.schimmel@amsterdamumc.nl
EM operator, maintenance Electron Microscopes, Epon, negative staining, SEM
Anita Grootemaat, M3-132, 64703, a.e.grootemaat@amsterdamumc.nl
EM operator ImmunoEM, Epon, negative staining
Sanne van der Niet, M3-131, s.vanderniet1@amsterdamumc.nl
PhD student NIH project
Meggie Hudspith, M3-131, 64703, m.r.hudspith@amsterdamumc.nl
Postddoc NWO project
Gabrielle Krebbers, M3-131, 65634, g.krebbers@amsterdamumc.nl
TEM diagnostics
Jeannette Pankras, M3-129, j.e.pankras@amsterdamumc.nl
TEM diagnostics
Students: from 2014
Job van den Dijssel
Ignė Kanopaitė
Cody van der Spek
Bastiaan Lodder
Inssaf Darraz
Jordy de Bakker
Eugenie Alvarez
Celine Haukes
Zihang Song
Janneke Hummelink
Sofie Rutten
Larissa Verkroost
Anna Dopler
Arno Loef
Sadhana Khanal
Abel Overzier
Elif Karakoç
Zehui Zhang
Edwin Schol
Marcella de Boer
Enzo Scutigliani
Jessie Snoep
2024
Pro-inflammatory T cells-derived cytokines enhance the maturation of the human fetal intestinal epithelial barrier. Giugliano FP, Navis M, Ouahoud S, Garcia TM, Kreulen IAM, Ferrantelli E, Meisner S, Vermeulen JLM, van Roest M, Billaud JN, Koster J, Dawood Y, de Bakker BS, Picavet-Havik DI, Schimmel IM, van der Wel NN, Koelink PJ, Wildenberg ME, Derikx JPM, de Jonge WJ, Renes IB, van Elburg RM, Muncan V.iScience. 2024 May 7;27(6):109909.
Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases. Bootsma S, Dings MPG, Kesselaar J, Helderman RFCPA, van Megesen K, Constantinides A, Moreno LF, Stelloo E, Scutigliani EM, Bokan B, Torang A, van Hooff SR, Zwijnenburg DA, Wouters VM, van de Vlasakker VCJ, Galanos LJK, Nijman LE, Logiantara A, Veenstra VL, Schlingemann S, van Piggelen S, van der Wel N, Krawczyk PM, Platteeuw JJ, Tuynman JB, de Hingh IH, Klomp JPG, Oubrie A, Snaebjornsson P, Medema JP, Oei AL, Kranenburg O, Elbers CC, Lenos KJ, Vermeulen L, Bijlsma MF.Cell Rep Med. 2024 May 21;5(5):101523.
Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis. Guo L, Zaharie SD, Marceline van Furth A, van der Wel NN, Grootemaat AE, Zhang L, Bugiani M, Kruger M, van der Kuip M, Lutter R.Tuberculosis (Edinb). 2024 May;146:102495.
CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders. van Karnebeek CDM, Tarailo-Graovac M, Leen R, Meinsma R, Correard S, Jansen-Meijer J, Prykhozhij SV, Pena IA, Ban K, Schock S, Saxena V, Pras-Raves ML, Drögemöller BI, Grootemaat AE, van der Wel NN, Dobritzsch D, Roseboom W, Schomakers BV, Jaspers YRJ, Zoetekouw L, Roelofsen J, Ferreira CR, van der Lee R, Ross CJ, Kochan J, McIntyre RL, van Klinken JB, van Weeghel M, Kramer G, Weschke B, Labrune P, Willemsen MA, Riva D, Garavaglia B, Moeschler JB, Filiano JJ, Ekker M, Berman JN, Dyment D, Vaz FM, Wassermann WW, Houtkooper RH, van Kuilenburg ABP.Genet Med. 2024 Feb 24;26(6):101104.
The impact of bed rest on human skeletal muscle metabolism. Eggelbusch M, Charlton BT, Bosutti A, Ganse B, Giakoumaki I, Grootemaat AE, Hendrickse PW, Jaspers Y, Kemp S, Kerkhoff TJ, Noort W, van Weeghel M, van der Wel NN, Wesseling JR, Frings-Meuthen P, Rittweger J, Mulder ER, Jaspers RT, Degens H, Wüst RCI.Cell Rep Med. 2024 Jan 16;5(1):101372.
2023
Platelets of COVID-19 patients display mitochondrial dysfunction, oxidative stress, and energy metabolism failure compatible with cell death. Léopold V, Chouchane O, Butler JM, Schuurman AR, Michels EHA, de Brabander J, Schomakers BV, van Weeghel M, Picavet-Havik DI, Grootemaat AE, Douma RA, Reijnders TDY, Klarenbeek AM, Appelman B; Amsterdam University Medical Center COVID-19 Biobank Study Groupd.vandebeek@amsterdamumc.nl; Wiersinga WJ, van der Wel NN, den Dunnen J, Houtkooper RH, Van’t Veer C, van der Poll T; Amsterdam University Medical Center COVID-19 Biobank Study Group.Res Pract Thromb Haemost. 2023 Sep 28;7(7):102213.
Nucleocapsid protein accumulates in renal tubular epithelium of a post-COVID-19 patient. Grootemaat AE, Wiersma N, van der Niet S, Schimmel IM, Florquin S, Reits EA, Miller SE, van der Wel NN.Microbiol Spectr. 2023 Dec 12;11(6)
IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans. Bakey Z, Cabrera OA, Hoefele J, Antony D, Wu K, Stuck MW, Micha D, Eguether T, Smith AO, van der Wel NN, Wagner M, Strittmatter L, Beales PL, Jonassen JA, Thiffault I, Cadieux-Dion M, Boyes L, Sharif S, Tüysüz B, Dunstheimer D, Niessen HWM, Devine W, Lo CW, Mitchison HM, Schmidts M, Pazour GJ.PLoS Genet. 2023 Jun 14;19(6):e1010796.
Spatial Transcriptional Mapping Reveals Site-Specific Pathways Underlying Human Atherosclerotic Plaque Rupture. Sun J, Singh P, Shami A, Kluza E, Pan M, Djordjevic D, Michaelsen NB, Kennbäck C, van der Wel NN, Orho-Melander M, Nilsson J, Formentini I, Conde-Knape K, Lutgens E, Edsfeldt A, Gonçalves I.J Am Coll Cardiol. 2023 Jun 13;81(23):2213-2227.
The immunological effects of intradermal particle-based vaccine delivery using a novel microinjection needle studied in a human skin explant model. Beaujean M, Uijen RF, Langereis JD, Boccara D, Dam D, Soria A, Veldhuis G, Adam L, Bonduelle O, van der Wel NN, Luirink J, Pedruzzi E, Wissink J, de Jonge MI, Combadière B.Vaccine. 2023 Mar 24;41(13):2270-2279.
Effect of long-term antihypertensive treatment on cerebrovascular structure and function in hypertensive rats. Naessens DMP, de Vos J, Richard E, Wilhelmus MMM, Jongenelen CAM, Scholl ER, van der Wel NN, Heijst JA, Teunissen CE, Strijkers GJ, Coolen BF, VanBavel E, Bakker ENTP.Sci Rep. 2023 Mar 1;13(1):3481.
A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages. Bedard M, van der Niet S, Bernard EM, Babunovic G, Cheng TY, Aylan B, Grootemaat AE, Raman S, Botella L, Ishikawa E, O’Sullivan MP, O’Leary S, Mayfield JA, Buter J, Minnaard AJ, Fortune SM, Murphy LO, Ory DS, Keane J, Yamasaki S, Gutierrez MG, van der Wel N, Moody DB.J Clin Invest. 2023 Mar 15;133(6):e161944.
Mitochondrial dysfunction in human hypertrophic cardiomyopathy is linked to cardiomyocyte architecture disruption and corrected by improving NADH-driven mitochondrial respiration. Nollet EE, Duursma I, Rozenbaum A, Eggelbusch M, Wüst RCI, Schoonvelde SAC, Michels M, Jansen M, van der Wel NN, Bedi KC, Margulies KB, Nirschl J, Kuster DWD, van der Velden J.Eur Heart J. 2023 Apr 1;44(13):1170-1185.
2022
Methanotrophy by a Mycobacterium species that dominates a cave microbial ecosystem. van Spanning RJM, Guan Q, Melkonian C, Gallant J, Polerecky L, Flot JF, Brandt BW, Braster M, Iturbe Espinoza P, Aerts JW, Meima-Franke MM, Piersma SR, Bunduc CM, Ummels R, Pain A, Fleming EJ, van der Wel NN, Gherman VD, Sarbu SM, Bodelier PLE, Bitter W. Nat Microbiol. 2022 Dec;7(12):2089-2100.
Hyperactivation of mTORC1 in a double hit mutant zebrafish model of tuberous sclerosis complex causes increased seizure susceptibility and neurodevelopmental abnormalities. De Meulemeester AS, Heylen L, Siekierska A, Mills JD, Romagnolo A, Van Der Wel NN, Aronica E, de Witte PAM.Front Cell Dev Biol. 2022 Sep 27;10:952832.
The phospholipid flippase ATP8B1 is required for lysosomal fusion in macrophages. Gómez-Mellado VE, Ho-Mok KS, van der Mark VA, van der Wel NN, Grootemaat AE, Verhoeven AJ, Elferink RPJO, Paulusma CC.Cell Biochem Funct. 2022 Dec;40(8):914-925.
Transfer dynamics of multi-resistance plasmids in Escherichia coli isolated from meat. Darphorn TS, Koenders-van Sintanneland BB, Grootemaat AE, van der Wel NN, Brul S, Ter Kuile BH.PLoS One. 2022 Jul 7;17(7):e0270205.
Harnessing solar power: photoautotrophy supplements the diet of a low-light dwelling sponge. Hudspith M, de Goeij JM, Streekstra M, Kornder NA, Bougoure J, Guagliardo P, Campana S, van der Wel NN, Muyzer G, Rix L.ISME J. 2022 Sep;16(9):2076-2086.
Neutrophil Extracellular Traps Do Not Induce Injury and Inflammation in Well-Differentiated RSV-Infected Airway Epithelium. Linssen RSN, Sridhar A, Moreni G, van der Wel NN, van Woensel JBM, Wolthers KC, Bem RA.Cells. 2022 Feb 24;11(5):785.
Lipid and Nucleocapsid N-Protein Accumulation in COVID-19 Patient Lung and Infected Cells. Grootemaat AE, van der Niet S, Scholl ER, Roos E, Schurink B, Bugiani M, Miller SE, Larsen P, Pankras J, Reits EA, van der Wel NN.Microbiol Spectr. 2022 Feb 23;10(1):e0127121.
Specific Silencing of Microglial Gene Expression in the Rat Brain by Nanoparticle-Based Small Interfering RNA Delivery. Guo S, Cázarez-Márquez F, Jiao H, Foppen E, Korpel NL, Grootemaat AE, Liv N, Gao Y, van der Wel N, Zhou B, Nie G, Yi CX.ACS Appl Mater Interfaces. 2022 Feb 2;14(4):5066-5079.
2021
Diverse ultrastructural landscape of atherosclerotic endothelium. Kluza E, Beldman TJ, Shami A, Scholl ER, Malinova TS, Grootemaat AE, van der Wel NN, Gonçalves I, Huveneers S, Mulder WJM, Lutgens E.Atherosclerosis. 2021 Dec;339:35-45.
Seizure-mediated iron accumulation and dysregulated iron metabolism after status epilepticus and in temporal lobe epilepsy. Zimmer TS, David B, Broekaart DWM, Schidlowski M, Ruffolo G, Korotkov A, van der Wel NN, van Rijen PC, Mühlebner A, van Hecke W, Baayen JC, Idema S, François L, van Eyll J, Dedeurwaerdere S, Kessels HW, Surges R, Rüber T, Gorter JA, Mills JD, van Vliet EA, Aronica E.Acta Neuropathol. 2021 Oct;142(4):729-759.
Impaired myelin production due to an intrinsic failure of oligodendrocytes in mTORpathies. Gruber VE, Lang J, Endmayr V, Diehm R, Pimpel B, Glatter S, Anink JJ, Bongaarts A, Luinenburg MJ, Reinten RJ, van der Wel N, Larsen P, Hainfellner JA, Rössler K, Aronica E, Scholl T, Mühlebner A, Feucht M.Neuropathol Appl Neurobiol. 2021 Oct;47(6):812-825.
Preservation of renal endothelial integrity and reduction of renal edema by aprotinin does not preserve renal perfusion and function following experimental cardiopulmonary bypass. Dekker NAM, van Leeuwen ALI, van Meurs M, Moser J, Pankras JE, van der Wel NN, Niessen HW, Vervloet MG, Vonk ABA, Hordijk PL, Boer C, van den Brom CE. Intensive Care Med Exp. 2021 Jun 25;9(1):30.
IL-1R1-Dependent Signals Improve Control of Cytosolic Virulent Mycobacteria In Vivo. van der Niet S, van Zon M, de Punder K, Grootemaat A, Rutten S, Moorlag SJCFM, Houben D, van der Sar AM, Bitter W, Brosch R, Hernandez Pando R, Pena MT, Peters PJ, Reits EA, Mayer-Barber KD, van der Wel NN.mSphere. 2021 May 5;6(3):e00153-21.
GCase and LIMP2 Abnormalities in the Liver of Niemann Pick Type C Mice. van der Lienden MJC, Aten J, Marques ARA, Waas ISE, Larsen PWB, Claessen N, van der Wel NN, Ottenhoff R, van Eijk M, Aerts JMFG.Int J Mol Sci. 2021 Mar 3;22(5):2532.
Control of septum thickness by the curvature of SepF polymers. Wenzel M, Celik Gulsoy IN, Gao Y, Teng Z, Willemse J, Middelkamp M, van Rosmalen MGM, Larsen PWB, van der Wel NN, Wuite GJL, Roos WH, Hamoen LW. Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2002635118.
2020
Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Schurink B, Roos E, Radonic T, Barbe E, Bouman CSC, de Boer HH, de Bree GJ, Bulle EB, Aronica EM, Florquin S, Fronczek J, Heunks LMA, de Jong MD, Guo L, du Long R, Lutter R, Molenaar PCG, Neefjes-Borst EA, Niessen HWM, van Noesel CJM, Roelofs JJTH, Snijder EJ, Soer EC, Verheij J, Vlaar APJ, Vos W, van der Wel NN, van der Wal AC, van der Valk P, Bugiani M.Lancet Microbe. 2020 Nov;1(7):e290-e299.
The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting. Tan JME, van der Stoel MM, van den Berg M, van Loon NM, Moeton M, Scholl E, van der Wel NN, Kovačević I, Hordijk PL, Loregger A, Huveneers S, Zelcer N.Cell Rep. 2020 Aug 4;32(5):107944.
Artificial Sporulation Induction (ASI) by kinA Overexpression Affects the Proteomes and Properties of Bacillus subtilis Spores. Tu Z, R Abhyankar W, N Swarge B, van der Wel N, Kramer G, Brul S, J de Koning L.Int J Mol Sci. 2020 Jun 17;21(12):4315.
Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30. Liu YJ, McIntyre RL, Janssens GE, Williams EG, Lan J, van Weeghel M, Schomakers B, van der Veen H, van der Wel NN, Yao P, Mair WB, Aebersold R, MacInnes AW, Houtkooper RH.J Cell Biol. 2020 Jun 1;219(6):e201907067.
ATF2 and ATF7 Are Critical Mediators of Intestinal Epithelial Repair. Meijer BJ, Giugliano FP, Baan B, van der Meer JHM, Meisner S, van Roest M, Koelink PJ, de Boer RJ, Jones N, Breitwieser W, van der Wel NN, Wildenberg ME, van den Brink GR, Heijmans J, Muncan V.Cell Mol Gastroenterol Hepatol. 2020;10(1):23-42.
2019
Mycobacterium tuberculosis releases an antacid that remodels phagosomes. Buter J, Cheng TY, Ghanem M, Grootemaat AE, Raman S, Feng X, Plantijn AR, Ennis T, Wang J, Cotton RN, Layre E, Ramnarine AK, Mayfield JA, Young DC, Jezek Martinot A, Siddiqi N, Wakabayashi S, Botella H, Calderon R, Murray M, Ehrt S, Snider BB, Reed MB, Oldfield E, Tan S, Rubin EJ, Behr MA, van der Wel NN, Minnaard AJ, Moody DB. Nat Chem Biol. 2019 Sep;15(9):889-899.
Nanoparticle-Aided Characterization of Arterial Endothelial Architecture during Atherosclerosis Progression and Metabolic Therapy. Beldman TJ, Malinova TS, Desclos E, Grootemaat AE, Misiak ALS, van der Velden S, van Roomen CPAA, Beckers L, van Veen HA, Krawczyk PM, Hoebe RA, Sluimer JC, Neele AE, de Winther MPJ, van der Wel NN, Lutgens E, Mulder WJM, Huveneers S, Kluza E. ACS Nano. 2019 Jul 10.
Liver disease predominates in a mouse model for mild human Zellweger spectrum disorder. Berendse K, Boek M, Gijbels M, Van der Wel NN, Klouwer FC, van den Bergh-Weerman MA, Shinde AB, Ofman R, Poll-The BT, Houten SM, Baes M, Wanders RJA, Waterham HR. Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1;1865(10):2774-2787.
Extravasation of Microspheres in a Rat Model of Silent Brain Infarcts. van der Wijk AE, Lachkar N, de Vos J, Grootemaat AE, van der Wel NN, Hordijk PL, Bakker ENTP, vanBavel E.Stroke. 2019 Jun;50(6):1590-1594.
Inhibition of autotransporter biogenesis by small molecules. Steenhuis M, Abdallah AM, de Munnik SM, Kuhne S, Sterk GJ, van den Berg van Saparoea B, Westerhausen S, Wagner S, van der Wel NN, Wijtmans M, van Ulsen P, Jong WSP, Luirink J. Mol Microbiol. 2019 Jul;112(1):81-98.
Eosinophils capture viruses, a capacity that is defective in asthma. Sabogal Piñeros YS, Bal SM, Dijkhuis A, Majoor CJ, Dierdorp BS, Dekker T, Hoefsmit EP, Bonta PI, Picavet D, van der Wel NN, Koenderman L, Sterk PJ, Ravanetti L, Lutter R. Allergy. 2019 Apr 1.
Expression patterns of endothelial permeability pathways in the development of the blood-retinal barrier in mice. van der Wijk AE, Wisniewska-Kruk J, Vogels IMC, van Veen HA, Ip WF, van der Wel NN, van Noorden CJF, Schlingemann RO, Klaassen I. FASEB J. 2019 Apr;33(4):5320-5333.
Maturing Human CD127+ CCR7+ PDL1+ Dendritic Cells Express AIRE in the Absence of Tissue Restricted Antigens. Fergusson JR, Morgan MD, Bruchard M, Huitema L, Heesters BA, van Unen V, van Hamburg JP, van der Wel NN, Picavet D, Koning F, Tas SW, Anderson MS, Marioni JC, Holländer GA, Spits H.Front Immunol. 2019 Jan 14;9:2902.
2018
Interfering With DNA Decondensation as a Strategy Against Mycobacteria. Scutigliani EM, Scholl ER, Grootemaat AE, Khanal S, Kochan JA, Krawczyk PM, Reits EA, Garzan A, Ngo HX, Green KD, Garneau-Tsodikova S, Ruijter JM, van Veen HA, van der Wel NN.Front Microbiol. 2018 Sep 5;9:2034.
Role of Peptidylarginine Deiminase 4 in Neutrophil Extracellular Trap Formation and Host Defense during Klebsiella pneumoniae-Induced Pneumonia-Derived Sepsis. Claushuis TAM, van der Donk LEH, Luitse AL, van Veen HA, van der Wel NN, van Vught LA, Roelofs JJTH, de Boer OJ, Lankelma JM, Boon L, de Vos AF, van ‘t Veer C, van der Poll T.J Immunol. 2018 Aug 15;201(4):1241-1252.
Nbeal2 Deficiency Increases Organ Damage but Does Not Affect Host Defense During Gram-Negative Pneumonia-Derived Sepsis.Claushuis TAM, de Stoppelaar SF, de Vos AF, Grootemaat AE, van der Wel NN, Roelofs JJTH, Ware J, Van’t Veer C, van der Poll T. Arterioscler Thromb Vasc Biol. 2018 Aug;38(8):1772-1784.
Mycobacteria employ two different mechanisms to cross the blood-brain barrier. van Leeuwen LM, Boot M, Kuijl C, Picavet DI, van Stempvoort G, van der Pol SMA, de Vries HE, van der Wel NN, van der Kuip M, van Furth AM, van der Sar AM, Bitter W. Cell Microbiol. 2018 Sep;20(9):e12858.
Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension. Palao T, Medzikovic L, Rippe C, Wanga S, Al-Mardini C, van Weert A, de Vos J, van der Wel NN, van Veen HA, van Bavel ET, Swärd K, de Waard V, Bakker EN. Cardiovasc Pathol. 2018 Jul – Aug;35:12-19.
Systemic inhibition of the membrane attack complex impedes neuroinflammation in chronic relapsing experimental autoimmune encephalomyelitis. Michailidou I, Jongejan A, Vreijling JP, Georgakopoulou T, de Wissel MB, Wolterman RA, Ruizendaal P, Klar-Mohamad N, Grootemaat AE, Picavet DI, Kumar V, van Kooten C, Woodruff TM, Morgan BP, van der Wel NN, Ramaglia V, Fluiter K, Baas F. Acta Neuropathol Commun. 2018 May 3;6(1):36.
Extracellular vesicles from human saliva promote hemostasis by delivering coagulant tissue factor to activated platelets. Yu Y, Gool E, Berckmans RJ, Coumans FAW, Barendrecht AD, Maas C, van der Wel NN, Altevogt P, Sturk A, Nieuwland R. J Thromb Haemost. 2018 Jun;16(6):1153-1163.
2017-
Bedussi B, van der Wel NN, de Vos J, van Veen H, Siebes M, VanBavel E, Bakker ENTP, Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways. J CEREBR BLOOD F MET 2017;37 (4):1374-1385 [PubMed]
Beldman TJ, Senders ML, Alaarg A, Pérez-Medina C, Tang J, Zhao Y, Fay F, Deichmöller J, Born B, Desclos E, van der Wel NN, Hoebe RA, Kohen F, Kartvelishvily E, Neeman M, Reiner T, Calcagno C, Fayad ZA, de Winther MPJ, Lutgens E, Mulder WJM, Kluza E, Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis. ACS NANO 2017;11 (6):5785-5799 [PubMed]
Gao Y, Vidal-Itriago A, Kalsbeek MJ, Layritz C, García-Cáceres C, Tom RZ, Eichmann TO, Vaz FM, Houtkooper RH, van der Wel N, Verhoeven AJ, Yan J, Kalsbeek A, Eckel RH, Hofmann SM, Yi CX, Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity. CELL REP 2017;20 (13):3034-3042 [PubMed]
Maat DS, Biggs T, Evans C, van Bleijswijk JDL, van der Wel NN, Dutilh BE, Brussaard CPD, Characterization and Temperature Dependence of Arctic Micromonas polaris Viruses. VIRUSES-BASEL 2017;9 (6):134 [PubMed]
van Zon M, de Punder K, van der Sar A, Brosch R, Pando RH, Grootemaat A , Tigchelaar-Gutter W, van der Wel N, Subcellular localization of M. tuberculosis in vivo and effect of the adaptive immunity. ULTRASTRUCT PATHOL 2017;41 (1):133 [PubMed]
Abhyankar WR, Kamphorst K, Swarge BN, van Veen H, van der Wel NN, Brul S, de Koster CG, de Koning LJ, The Influence of Sporulation Conditions on the Spore Coat Protein Composition of Bacillus subtilis Spores. FRONT MICROBIOL 2016;7:1636 [PubMed]
Ates LS, van der Woude AD, Bestebroer J, van Stempvoort G, Musters RJP, Garcia-Vallejo JJ, Picavet DI, Weerd Rvd, Maletta M, Kuijl CP, van der Wel NN, Bitter W, The ESX-5 System of Pathogenic Mycobacteria Is Involved In Capsule Integrity and Virulence through Its Substrate PPE10. PLOS PATHOG 2016;12 (6):e1005696 [PubMed]
Potze L, Di Franco S, Grandela C, Pras-Raves ML, Picavet DI, van Veen HA, van Lenthe H, Mullauer FB, van der Wel NN, Luyf A, van Kampen AHC, Kemp S, Everts V, Kessler JH, Vaz FM, Medema JP, Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification. ONCOGENE 2016;35 (4):427-437 [PubMed]
Ribeiro CMS, Sarrami-Forooshani R, Setiawan LC, Zijlstra-Willems EM, van Hamme JL, Tigchelaar W, van der Wel NN, Kootstra NA, Gringhuis SI, Geijtenbeek TBH, Receptor usage dictates HIV-1 restriction by human TRIM5α in dendritic cell subsets. NATURE 2016;540 (7633):448-452 [PubMed]
van der Spek AH, Bloise FF, Tigchelaar W, Dentice M, Salvatore D, van der Wel NN, Fliers E, Boelen A, The Thyroid Hormone Inactivating Enzyme Type 3 Deiodinase is Present in Bactericidal Granules and the Cytoplasm of Human Neutrophils. ENDOCRINOLOGY 2016;157 (8):3293-3305 [PubMed]
Zheng L, Abhyankar W, Ouwerling N, Dekker HL, van Veen H, van der Wel NN, Roseboom W, de Koning LJ, Brul S, de Koster CG, Bacillus subtilis Spore Inner Membrane Proteome. J PROTEOME RES 2016;15 (2):585-594 [PubMed]
Daleke-Schermerhorn MH, Felix T, Soprova Z, ten Hagen-Jongman CM, Vikström D, Majlessi L, Beskers J, Follmann F, de Punder K, van der Wel NN, Baumgarten T, Pham TV, Piersma SR, Jiménez CR, van Ulsen P, de Gier JW, Leclerc C, Jong WSP, Luirink J, Decoration of outer membrane vesicles with multiple antigens by using an autotransporter approach. APPL ENVIRON MICROB 2014;80 (18):5854-5865 [PubMed]
Jong WSP, Daleke-Schermerhorn MH, Vikström D, ten Hagen-Jongman CM, de Punder K, van der Wel NN, van de Sandt CE, Rimmelzwaan GF, Follmann F, Agger EM, Andersen P, de Gier JW, Luirink J, An autotransporter display platform for the development of multivalent recombinant bacterial vector vaccines. MICROB CELL FACT 2014;13:162 [PubMed]
Stoop EJ, Mishra AK, Driessen NN, van Stempvoort G, Bouchier P, Verboom T, van Leeuwen LM, Sparrius M, Raadsen SA, van Zon M, van der Wel NN, Besra GS, Geurtsen J, Bitter W, Appelmelk BJ, van der Sar AM. Mannan core branching of lipo(arabino)mannan is required for mycobacterial virulence in the context of innate immunity. Cell Microbiol. 2013 Dec;15(12):2093-108. PMID: 23902464
van der Woude AD, Mahendran KR, Ummels R, Piersma SR, Pham TV, Jiménez CR, de Punder K, van der Wel NN, Winterhalter M, Luirink J, Bitter W, Houben EN. Differential detergent extraction of mycobacterium marinum cell envelope proteins identifies an extensively modified threonine-rich outer membrane protein with channel activity. J Bacteriol. 2013 May;195(9):2050-9. PMID: 23457249
Jong WS, Soprova Z, de Punder K, ten Hagen-Jongman CM, Wagner S, Wickström D, de Gier JW, Andersen P, van der Wel NN, Luirink J. A structurally informed autotransporter platform for efficient heterologous protein secretion and display. Microb Cell Fact. 2012 Jun 18;11:85. PMID: 22709508
Houben D, Demangel C, van Ingen J, Perez J, Baldeón L, Abdallah AM, Caleechurn L, Bottai D, van Zon M, de Punder K, van der Laan T, Kant A, Bossers-de Vries R, Willemsen P, Bitter W, van Soolingen D, Brosch R, van der Wel N, Peters PJ. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria. Cell Microbiol. 2012 Aug;14(8):1287-98. PMID: 22524898
Weerdenburg EM, Abdallah AM, Mitra S, de Punder K, van der Wel NN, Bird S, Appelmelk BJ, Bitter W, van der Sar AM. ESX-5-deficient Mycobacterium marinum is hypervirulent in adult zebrafish. Cell Microbiol. 2012 May;14(5):728-39. PMID: 22256857
Abdallah AM, Bestebroer J, Savage ND, de Punder K, van Zon M, Wilson L, Korbee CJ, van der Sar AM, Ottenhoff TH, van der Wel NN, Bitter W, Peters PJ. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation. J Immunol. 2011 Nov 1;187(9):4744-53. PMID: 21957139 Free Article
Daleke MH, Cascioferro A, de Punder K, Ummels R, Abdallah AM, van der Wel N, Peters PJ, Luirink J, Manganelli R, Bitter W. Conserved Pro-Glu (PE) and Pro-Pro-Glu (PPE) protein domains target LipY lipases of pathogenic mycobacteria to the cell surface via the ESX-5 pathway. J Biol Chem. 2011 May 27;286(21):19024-34. PMID: 21471225
Sani M, Houben EN, Geurtsen J, Pierson J, de Punder K, van Zon M, Wever B, Piersma SR, Jiménez CR, Daffé M, Appelmelk BJ, Bitter W, van der Wel N, Peters PJ. Direct visualization by cryo-EM of the mycobacterial capsular layer: a labile structure containing ESX-1-secreted proteins. PLoS Pathog. 2010 Mar 5;6. PMID: 20221442
Weerdenburg EM, Peters PJ, van der Wel NN. How do mycobacteria activate CD8+ T cells? Trends Microbiol. 2010 Jan;18(1):1-10. PMID: 19962899
Abdallah AM, Savage ND, van Zon M, Wilson L, Vandenbroucke-Grauls CM, van der Wel NN, Ottenhoff TH, Bitter W. The ESX-5 secretion system of Mycobacterium marinum modulates the macrophage response. J Immunol. 2008 Nov 15;181(10):7166-75. PMID: 18981138
Hava DL, van der Wel N, Cohen N, Dascher CC, Houben D, León L, Agarwal S, Sugita M, van Zon M, Kent SC, Shams H, Peters PJ, Brenner MB. Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11281-6. PMID: 18685099
van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J, Brenner M, Peters PJ. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells. Cell. 2007 Jun 29;129(7):1287-98. PMID: 17604718
Touret N, Paroutis P, Terebiznik M, Harrison RE, Trombetta S, Pypaert M, Chow A, Jiang A, Shaw J, Yip C, Moore HP, van der Wel N, Houben D, Peters PJ, de Chastellier C, Mellman I, Grinstein S. Quantitative and dynamic assessment of the contribution of the ER to phagosome formation. Cell. 2005 Oct 7;123(1):157-70. PMID: 16213220
Boes M, van der Wel N, Peperzak V, Kim YM, Peters PJ, Ploegh H. In vivo control of endosomal architecture by class II-associated invariant chain and cathepsin S. Eur J Immunol. 2005 Sep;35(9):2552-62. PMID: 16094690
van der Wel NN, Fluitsma DM, Dascher CC, Brenner MB, Peters PJ. Subcellular localization of mycobacteria in tissues and detection of lipid antigens in organelles using cryo-techniques for light and electron microscopy. Curr Opin Microbiol. 2005 Jun;8(3):323-30. Review. PMID: 15939357
Angénieux C, Fraisier V, Maître B, Racine V, van der Wel N, Fricker D, Proamer F, Sachse M, Cazenave JP, Peters P, Goud B, Hanau D, Sibarita JB, Salamero J, de la Salle H. The cellular pathway of CD1e in immature and maturing dendritic cells. Traffic. 2005 Apr;6(4):286-302. PMID: 15752135
Baas AF, Kuipers J, van der Wel NN, Batlle E, Koerten HK, Peters PJ, Clevers HC. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD Cell. 2004 Feb 6;116(3):457-66. PMID: 15016379
Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM. Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J Biol Chem. 2004 Apr 30;279(18):18792-8. PMID: 14970223
Cernadas M, Sugita M, van der Wel N, Cao X, Gumperz JE, Maltsev S, Besra GS, Behar SM, Peters PJ, Brenner MB. Lysosomal localization of murine CD1d mediated by AP-3 is necessary for NK T cell development. J Immunol. 2003 Oct 15;171(8):4149-55. PMID: 14530337
van der Wel NN, Sugita M, Fluitsma DM, Cao X, Schreibelt G, Brenner MB, Peters PJ. CD1 and major histocompatibility complex II molecules follow a different course during dendritic cell maturation. Mol Biol Cell. 2003 Aug;14(8):3378-88. PMID: 12925770
Puertollano R, van der Wel NN, Greene LE, Eisenberg E, Peters PJ, Bonifacino JS. Morphology and dynamics of clathrin/GGA1-coated carriers budding from the trans-Golgi network. Mol Biol Cell. 2003 Apr;14(4):1545-57. PMID: 12686608
Bertens P, Heijne W, van der Wel N, Wellink J, van Kammen A. Studies on the C-terminus of the Cowpea mosaic virus movement protein. Arch Virol. 2003 Feb;148(2):265-79. PMID: 12556992
Cao X, Sugita M, Van Der Wel N, Lai J, Rogers RA, Peters PJ, Brenner MB. CD1 molecules efficiently present antigen in immature dendritic cells and traffic independently of MHC class II during dendritic cell maturation. J Immunol. 2002 Nov 1;169(9):4770-7.PMID: 12391186
Sugita M, van Der Wel N, Rogers RA, Peters PJ, Brenner MB. CD1c molecules broadly survey the endocytic system. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8445-50. PMID: 10890914
van der Wel NN, Goldbach RW, van Lent JW. The movement protein and coat protein of alfalfa mosaic virus accumulate in structurally modified plasmodesmata. Virology. 1998 May 10;244(2):322-9. PMID: 9601503
Kasteel DT, van der Wel NN, Jansen KA, Goldbach RW, van Lent JW. Tubule-forming capacity of the movement proteins of alfalfa mosaic virus and brome mosaic virus. J Gen Virol. 1997 Aug;78 ( Pt 8):2089-93. PMID: 9267012