Antibiotics resistance is one of the most important modern health issue. With the apparition of pan-resistant bacteria (meaning resistant to all the commercially available antibiotics), it is urgent and crucial to find new antibiotics, but new fighting alternatives as well. In this context, the bacterial pathogen Acinetobacter baumannii was ranked as a top priority pathogen due to its worrying resistance arsenal (WHO 2017 and CDC 2019). Besides its antibiotic resistances, A. baumannii bacteria are highly resistant to environmental stresses and the human immune system. The study of this Gram-negative bacterium is rendered even more difficult by the fact that these bacteria are very heterogeneous, characterized by a dynamic genome due to horizontal gene transfer by natural competence. In other words, they can take up extracellular DNA fragments and integrate them in their genome to evolve and quickly acquire resistance genes. Seeing this whole diversity amongst A. baumannii isolates (both at the phenotypic and genotypic levels), it is not surprising that, nowadays, the virulence and the mechanisms of stress resistance still remain to be understood.A better understanding of the resistances mechanisms (not only for antibiotics) is crucial to better fight this multidrug resistant pathogen.
In this context, we wanted to first determine if the few classical reference strains of A. baumannii available represent good bacterial models to study the current and modern multidrug clinical isolates. Then, based on our phenotypic observations, we generate an experimental strategy to work on the capsule production. We could also study this phenomenon using a new host-pathogen interaction based on the phagocytic pressure exerted by the amoeba called Acanthamoeba castellanii. The aim being to develop a new infection model to study common resistance mechanism, shared by the majority of the current and modern clinical isolates. A better understanding of the resistance mechanisms is important for the development of further antimicrobial strategies.Beside this fundamental part of the project, we wanted to follow a more applied strategy, and also screened a compounds library to find new antibiotics against multidrug-resistant A. baumannii bacteria.
