VUMC, dpt. MMI
tnv W. Bitter
De Boelelaan 1107
1081 HZ Amsterdam
O2 gebouw, 06E49
Wilbert Bitter is full Professor of Molecular and Medical Microbiology at the VU university and VU university medical center. After his MSc study in Biology, he completed his PhD in Molecular Microbiology at the University of Utrecht in 1992. In 1993, he won the Unilever research award for young scientist. He then held a postdoc position in parasitology at the Dutch Cancer Institute (NKI). In 1995, he returned to the University of Utrecht for a postdoc and subsequently an assistant professor position. In 2001 he started his own group in the VU university medical center and since 2010 he is a full professor. Wilbert Bitter is a member of the Scientific Committee of the Dutch Society of Medical Microbiology (NVMM), and is associate editor of FEMS Microbiology Reviews.
My research focuses on virulence and pathogenesis of the tubercle bacillus, Mycobacterium tuberculosis. Tuberculosis is an ancient disease, but, with an estimated 1.5 million deaths per year, still a major health problem today. Although most forms tuberculosis can be treated with antibiotics, a long treatment regimen of minimally 6 months is needed. Furthermore, the available vaccine strain does not protect adults very well against lung tuberculosis. Despite its importance, our knowledge of how tubercle bacilli actually survive inside the human host and cause disease is still fairly limited. This is mainly due to the fact that the mycobacteria are highly unusual bacteria. This difference is exemplified by the cell envelope organization, which is radically different form all other bacterial model species. In our laboratory we are studying the interaction of the tubercle bacilli with its host, with an emphasis on the mycobacterial cell wall and secreted proteins. For most experiments we use the fish pathogen Mycobacterium marinum as a model and the zebrafish as a host organism.
In recent years we discovered a major secretion pathway in mycobacteria, called ESX-5, which is responsible for the secretion of dozens of highly unusual proteins of the PE and PPE protein families. ESX-5 mutants show a dramatic difference in immune modulation and virulence. ESX-5 belongs to a novel and special secretion pathway, known as type VII secretion systems. My main interest is to (i) unravel the inner workings of the ESX-5 secretion system, (ii) determine the function of ESX-5 substrates in virulence (iii) use the ESX-5 secretion systems to achieve efficient heterologous protein secretion in mycobacteria. Our results will be used to generate novel vaccine candidates to treat the white plague of mankind. Variants of type VII secretion systems are also present in other (pathogenic) bacteria and we are also aiming to tackle these novel systems. Another initiative is to use our knowledge of the mycobacterial cell wall and it secretion systems and especially our special zebrafish infection model to generate and test new antimicrobial compounds.