Area(s) of interest
- Molecular bacteriology
- Clostridium difficile gene expression
- Resistance to antibiotics
Department of Medical Microbiology
PI Molecular biology of Clostridium difficile
In order to successfully infect hosts, pathogenic bacteria such as Clostridium difficile need to be able to respond to a variety of environmental conditions. In order to do so, they sense the surroundings and adjust their gene expression accordingly. Once a host is infected, a gene expression program is started that results in disease (e.g. the production of toxins) and – ultimately – dissemination of the pathogen (for instance through highly resistant spores in the case of C. difficile). A detailed understanding of these processes is a first step in combating the pathogen.
One environmental stress, antimicrobialtreatment, is of particular interest. C. difficile demonstrates extensive resistance to commonly used antimicrobial therapies and is increasingly resistant to those that are at present still effective. It is therefore of great importance to identify the mechanisms that are responsible for the resistance, and to find new targets for antimicrobial development.
Wiep Klaas Smits (1979) obtained his Masters degree in Biology (from the University of Groningen) in 2002, specializing in genetics and microbiology. Subsequently, he performed his PhD research at the Department of Molecular Genetics of the Faculty of Mathematics and Natural Sciences (promotor: Prof. Dr. O.P. Kuipers), resulting in the thesis “To be competent or not: an inquiry into the molecular basis of bacterial differentiation” and a cum laude defense at the University of Groningen in 2007. For his thesis research he received Kiem prize of the Dutch Society of Microbiology and the Nat L. Sternberg Thesis Prize of Cold Spring Harbor Laboratories.
After obtaining his PhD, dr. Smits worked for three years as postdoc at the Massachusetts Institute of Technology in Cambridge (USA) in the lab of Prof. A. Grossmann, in part funded by a Rubicon fellowship from the Netherlands Organisation for Scientitic Research (NWO). Since March 2010 he works as a research associate at the Leiden University Medical Center (LUMC)and received a VENI fellowship from NWO and a Gisela Thier fellowship from the LUMC. For his ongoing research he received a VIDI fellowship from NWO.
Dr. Smits’ research focuses on the reconstruction of gene regulatory network of the Gram postitive pathogenic bacterium Clostridium difficile and the identification of potential targets for antibiotic development (DNA replication). The research employers a variety of genetic, molecular and biochemical techniques, which in part are developed within the group itself.
Dr. Smits published around 30 articles in peer-reviewed journals and one book chapter. In the past he has multiple times served as an ad hoc reviewer for various scientific journals.
van Eijk E, Paschalis V, Green M, Friggen AH, Larson MA, Spriggs K, Briggs GS, Soultanas P, Smits WK. Primase is required for helicase activity and helicase alters the specificity of primase in the enteropathogen Clostridium difficile. Open Biol. 2016; 6:160272
Oliveira Paiva AM, Friggen AH, Hossein-Javaheri S, Smits WK. The Signal Sequence of the Abundant Extracellular Metalloprotease PPEP-1 Can Be Used to Secrete Synthetic Reporter Proteins in Clostridium difficile. ACS Synth Biol. 2016 Jun 23. [Epub ahead of print]
Smits WK, Lyras D, Lacy DB, Wilcox MH , Kuijper EJ. Clostridium difficile infection. Nature Reviews Disease Primers 2; 16020 (2016).
Browne HP, Anvar SY, Frank J, Lawley TD, Roberts AP, Smits WK. Complete genome sequence of BS49 and draft genome sequence of BS34A, Bacillus subtilis strains carrying Tn916. FEMS Microbiol Lett. 2015 Jan;362(3):1-4.
Bakker D, Buckley AM, de Jong A, van Winden VJ, Verhoeks JP, Kuipers OP, Douce GR, Kuijper EJ, Smits WK, Corver J. The HtrA-like protease CD3284 modulates virulence of Clostridium difficile. Infect Immun. 2014 Oct;82(10):4222-32.
Pettit LJ, Browne HP, Yu L, Smits WK, Fagan RP, Barquist L, Martin MJ,Goulding D, Duncan SH, Flint HJ, Dougan G, Choudhary JS, Lawley TD. Functional genomics reveals that Clostridium difficile Spo0A coordinates sporulation, virulence and metabolism. BMC Genomics. 2014; 15:160.
Smits WK. Hype or hypervirulence: a reflection on problematic C. difficile strains. Virulence. 2013; 4:592-6.
Rosenbusch KE, Bakker D, Kuijper EJ, Smits WK. C. difficile 630Δerm Spo0A regulates sporulation, but does not contribute to toxin production, by direct high-affinity binding to target DNA. PLoS One. 2012; 7:e48608.
Bakker D, Smits WK, Kuijper EJ, Corver J. TcdC does not significantly repress toxin expression in Clostridium difficile 630ΔErm. PLoS One. 2012; 7:e43247.
Smits WK, Merrikh H, Bonilla CY, Grossman AD. Primosomal proteins DnaD and DnaB are recruited to chromosomal regions bound by DnaA in Bacillus subtilis.J Bacteriol. 2011; 193:640-8.
Smits WK, Grossman AD. The transcriptional regulator Rok binds A+T-rich DNA and is involved in repression of a mobile genetic element in Bacillus subtilis. PLoS Genet. 2010; 6:e1001207.
Smits WK, Goranov AI, Grossman AD. Ordered association of helicase loader proteins with the Bacillus subtilis origin of replication in vivo. Mol Microbiol. 2010; 75:452-61.
Leiden University Medical Center
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