Tuberculosis host pathogen interactions
In 2001 Wilbert Bitter founded the tuberculosis research group at the VUmc. Our vision is that by understanding the cell envelope of M. tuberculosis we will uncover new tools to combat this pathogen. To speed up research on this dangerous and enigmatic pathogen, most work is first performed on the fish pathogen Mycobacterium marinum, which is then translated to the tubercle bacillus. Wilbert’s group was the first to describe the function of the ESX-5 protein secretion system in tuberculosis. Subsequently we uncovered the composition and structure of type VII secretion systems (ESX-5) and the secretion signal for substrates. To study host-pathogen interaction we are using zebrafish larvae as an infection model. In recent years we also started to work on the identification of antimicrobial compounds. The zebrafish larvae model was shown to be ideally suited for antibiotic research and is now also applied to other pathogens.
Research team
Wilbert Bitter obtained his PhD in Molecular Microbiology in 1992 (Utrecht University). He is a full professor at the VU and AUMC since 2010.
He is currently running both a research unit at the MMI department of Amsterdam UMC (see below) and one at the A-LIFE - Molecular Microbiology of the Amsterdam UMC.
In total (https://aimms.vu.nl/en/research/research-groups/molecular-microbiology/index.aspx).
He is a director of the Master Biomolecular Sciences at the Amsterdam UMC (location VU) and holds a Tutu chair in Biology.
- PhD Renate van Belle Van den Berg,Teacher & master coordinator with senior teaching qualification
- PhD Susanna Commandeur, NWO-Veni laureate studying Mtb persistence and lipid vesicle production
- Ing Roy Ummels, Expert in (myco)bacterial genomics and BSL3
- Ing Marion Sparrius, Expert in bacterial genetic screens
- MSc Aniek Meijers, Uncovering the role of surface PE proteases in Mtb virulence
- MSc Sita Coenraads, Mechanism of plasmid conjugation in pathogenic mycobacteria
- MSc Gina Schouten, Antimicrobial peptides, their activity in vivo and their targets
- MSc Yuwei Ding, New approaches to study cell envelope proteins of Mtb
- MSc Robin Lissner, Role of lipoproteins in pathogenic mycobacteria
Other members, see groups of Alex Speer, Coen Kuijl and Edith Houben (VU)
- Four of the PhD students that Wilbert Bitter has (co)supervised have won the Westerdijk award for best microbiology thesis of that year.
Publications
Wilbert Bitter (amsterdamumc.org)
- Structure and dynamics of a mycobacterial type VII secretion system. Bunduc CM et al. Nature. 2021. doi: 10.1038/s41586-021-03517-z
- Mycobacterium tuberculosis Toxin CpnT Is an ESX-5 Substrate and Requires Three Type VII Secretion Systems for Intracellular Secretion. Izquierdo Lafuente B et al. mBio. 2021 12:e02983-20. doi: 10.1128/mBio.02983-20.
- Type VII Secretion Substrates of Pathogenic Mycobacteria Are Processed by a Surface Protease. Burggraaf MJ et al. mBio. 2019 10:e01951-19. doi: 10.1128/mBio.01951-19.
- Mutations in ppe38 block PE_PGRS secretion and increase virulence of Mycobacterium tuberculosis. Ates LS et al. Nat Microbiol. 2018 3:181-188. doi: 10.1038/s41564-017-0090-6.
- EspH is a hypervirulence factor for Mycobacterium marinum and essential for the secretion of the ESX-1 substrates EspE and EspF.
- Phan TH, van Leeuwen LM et al. PLoS Pathog. 2018 14:e1007247. doi: 10.1371/journal.ppat.1007247.
Publications
Wilfred Bitter - Publications
Email: w.bitter@amsterdamumc.nl