Pathogenic microbes

Bruxelles Woluwe

The main objective of our research team is to identify and isolate pharmacologically active products in plants from different countries and validate their traditional uses. We chose to focus particularly on medicinal plants and their constituents with antimicrobial (on Staphylococcus aureus, Pseudomonas aeruginosa, …) and antiparasitic (on Trypanosoma, Plasmodium, Leishmania) activities, as well as compounds inhibiting bacteria/parasites resistance, and to study their targets. These works are especially realized in collaboration with TFAR.
Contact : Joëlle Quetin-Leclercq (GNOS)

The right identification and quality controls of raw materials and plant extracts are crucial to guarantee their efficacy and safety. Quantification of these compounds in biological fluids is also necessary for further studies. Therefore, our team develops and validates methods to separate, identify and quantify active molecules in plant extracts or biological fluids based on different chromatographic techniques (HPTLC-MS, UHPLC-DAD, MS and MRMS, GC-FID, GC-MS). Moreover, the laboratory is officially agreed by the Federal Agency for Medicine and Health Products for the quality control of drugs. Contact : Joëlle Quetin-Leclercq

HIV treatment is challenging not only due to the high propensity for drug-drug interaction between antiretrovirals but also due to interactions with other co-administrated drugs, which situation is more the rule than the exception as HIV-infected patients are very frequently poly-medicated. Furthermore, hereditary alterations in metabolism exist and might be responsible, at least partially, for the inter-individual variability observed in the exposure to the drug despite a fixed-dose regimen. This raises the question about the appropriateness of a fixed dose regimen for every patient and highlights the need of identifying PK/PD predictors. This is the project thesis of Gabriel Stillemans (supervisor professors Laure Elens and Vincent Haufroid) that is focusing on the factors affecting the pharmacokinetics of Darunavir a second-generation potent protease inhibitor (PI), approved in 2008 for treatment of naïve patients. The study is entitled “Optimization of Darunavir therapy through population pharmacokinetic modeling, simulations and dosage guidelines”

New antibiotics
Resistance of bacteria to currently available antibiotics becomes a major problem worldwide, with untreatable infections starting to threaten patients. In this context, the group of cellular and molecular pharmacology (Françoise Van Bambeke and Marie-Paule Mingeot-Leclercq; TFAR) is evaluating new antibiotics or adjuvant therapies (inhibitors of resistance or of virulence) against multi-resistant pathogens and is also deciphering their mechanism of action. Among the new compounds investigated, some of them are antibiotics directed against innovative, unexploited targets (designed and synthesized by the group of medicinal chemistry of Raphaël Frederick) or natural substances extracted from plants used in traditional medicine (collaboration with Joëlle Quetin-Leclercq; pharmacognosy).

Antibiotic use in the clinics can be optimized through individualized dosing in order to maximize the probability of reaching therapeutic blood levels while at the same time limiting the risks of adverse effects. In the research group on Translational Research from Experimental and Clinical Pharmacology to Treatment Optimization (TFAR), clinical pharmacists are studying antibiotic pharmacokinetics in specific patients’ populations (children, intensive care, hemodialysis) in order to provide guidance for dosing optimization based on therapeutic monitoring coupled to dosing algorithms. They also examine how to rationalize antibiotic use in specific situations (prophylaxis of surgical procedures) and look for risk factors for developing toxicities. This work is performed by PhD students working under the co-supervision of to investigators of the group (O. Dalleur, L. Elens, A. Spinewine, F. Van Bambeke).

Beside resistance, tolerance to antibiotics also participates to therapeutic failure. Tolerance is due to the capacity of bacteria to adopt specific lifestyles like intracellular survival or biofilm, which are poorly responsive to antibiotics. It can be explained by a lack of access of the antibiotics to the bacteria localized in these protected niches together with a switch to a dormant phenotype that is not susceptible to antibiotics. The aim of the research performed in the group of Françoise Van Bambeke (cellular and molecular pharmacology; TFAR) is precisely to elucidate why and how bacteria become tolerant to antibiotics in these specific situations and to propose and to test innovative therapeutic strategies in this context. In parallel, strategies aiming at reducing bacterial virulence and at modulating host inflammatory response are also examined.

Profs Delzenne, Cani and Bindels are co-leading collaborative and interdisciplinary research projects dedicated to unravel the mechanisms linking the gut microbiota and host metabolism in several pathological contexts. Using innovative technologies, they investigate the role of specific bacteria (e.g. Akkermansia, Lactobacillus, Faecalibacterium, Bifidobacterium species), gut peptides, bacterial metabolites and gut microbiota-targeting foods and drugs in several metabolic disorders. Our ultimate goal is to offer a better understanding of the crosstalk between gut microbes and their host in physiological and pathophysiological contexts, in order to pinpoint new therapeutic targets and tools for the treatment of metabolic diseases through the modulation of the gut microbiota.

Harnessing the immune system to fight cancer is an attractive strategy. Prof V. Préat, Dr G. Vandermeulen, and their team aim at optimizing DNA vaccines to specifically treat tumors. They improve both the vaccine itself, at the molecular point of view, and the systems that allow its delivery, in particular electroporation. Their latest research exploits the properties of viral proteins which are engineered to efficiently present tumor antigens to the immune system. The project aims to provide a potent and versatile nucleic acid-based platform able to target several cancers. In parallel, Prof. R. Vanbever explores the potential of the pulmonary route for the local delivery of vaccine adjuvants.