The Van der Henst lab focuses on multidrug-resistant bacteria, with a clear emphasis on the Gram-negative bacterium Acinetobacter baumannii. This nosocomial pathogen possesses a worrying and well-supplied resistance arsenal. In addition to increasing antibiotic resistances, A. baumannii thrives within hospital settings, relying on its resistances against disinfection procedures and environmental stresses. On top of that, A. baumannii virulence deserves to be better characterized. We aim to better understand the resistance and virulence arsenals of A. baumannii, while in parallel dedicating efforts in impairing them.

 A. baumannii virulence is based on a "resist and persist" strategy, hence resistance and virulence are intrinsically linked.

A. baumannii resistance arsenal

We decipher the molecular mechanisms governing bacterial resistances by combining phenotypic characterization with whole genome sequencing data using reference strains and recent clinical isolates. The main targeted mechanisms studied are involved in desiccation, disinfectant, serum and phagocytic resistances. The factors identified represent new targets for a priori screening of antiresistance compounds.

A. baumannii virulence arsenal

Another part of our research studies A. baumannii virulence, with an emphasis on the polysaccharide capsule. We compare the levels of capsule production in the reference strains and in the current clinical isolates, their heterogeneity and their potential involvement in A. baumannii virulence using in vitro and in vivo infection models. The virulence factors identified represent new targets for the discovery of new antivirulence molecules.

Drug discovery using an in-house validated collection of modern clinical isolates

In parallel of the fundamental part that aims at a better understanding of the resistance and virulence capabilities of A. baumannii, medium to high-throughput screens are undertaken. The aims are the identification of new antibiotic, antiresistance or antivirulence compounds that are active against the majority of the current multidrug-resistant clinical isolates of A. baumannii. Efficient screening approaches using population and single-cell levels analyses, with and without a priori, are implemented directly on the bacteria themselves, or using a host-pathogen interaction context.

Host-pathogen interactions & infection models used to better understand the virulence and the resistance of Acinetobacter baumannii

- In vivo: Galleria mellonella.

- In vitro: The amoeba Acanthamoeba castellanii, macrophages and epithelial cells.