Han Remaut

‘Structural biology of Helicobacter pylori virulence factors’

Han Remaut was born in 1976 in the United States. He obtained a Master of Science degree in Biochemistry at Ghent University, Belgium in 1998, followed by a PhD in Biochemistry in 2003. As postdoctoral scientist, he then joined the lab of Prof. Gabriel Waksman at the Institute of Structural Molecular Biology, Birkbeck College, London.

For most pathogenic bacteria, a crucial initial step in the establishment of infection is the recognition and colonization of the host tissue by specific attachment via surface-exposed adhesion molecules. In gram-negative bacteria, these adhesins are displayed on the outer membrane as single proteins (e.g. autotransporters or two-partner secretion systems) or can be incorporated into filamentous polymers (chaperone/usher pili, type II pili, type IV secretion pili and curli). Adhesin-mediated attachment can simply serve as a means of avoiding clearance through mechanical shear, or can trigger more complex host responses like cytoskeleton reorganization and cell invasion, or provide the required proximity to the host cell to enable other virulence mechanisms to come into action (ea. effecter injection through type III and type IV secretion systems).

In an era of increased antibiotics resistance and difficulties in controlling hospital-acquired infections, it is essential to gain a better understanding of the fundamental principles governing the infectious process. The new group will study the structural molecular biology of bacterial adhesins and cell surface filaments with respect to their function in bacterial pathogenesis, with the ultimate aim of developing a new generation of virulence-targeted antimicrobials.

Virulence-targeted drug design is a novel concept in the development of new generation antimicrobials. Targeting virulence factors forms a potential alternative means of fighting infectious disease by selectively disarming pathogens, without placing immediate selective pressure on the bacteria. Due to its extreme persistence in the host and the known involvement of a complex adherence profile in maintaining infection, Helicobacter pylori forms an ideal proof-of-principle case for the development of anti-adhesin drugs.

Helicobacter pylori is a widespread human pathogen that is the leading cause of chronic gastritis and is associated with the development of peptic ulcers and gastric cancer. Current medical guidelines advocate Helicobacter eradication therapy in peptic ulcer disease, low-grade gastric MALT lymphoma and after gastric cancer resection. Because Helicobacter pylori is one of the most significant risk factors for gastric cancer, H. pylori eradication has been proposed as a possible primary chemopreventive strategy to reduce gastric cancer incidence. However, the alarming increase of antibiotic resistance in H. pylori strains has serious implications for current and future antibiotic-based therapies. In addition, only 10-20% of Helicobacter infections will ever progress into clinical disease. A mounting body of evidence indicates disease outcome is highly strain specific and is a function of a limited number of virulence factors. The development of anti-virulence therapies targeting HP adhesins has the potential for the broad-scale selective clearance of pathogenic HP strains only.