FEDER - URN - CELLECT - EMERGENT
Kohesio
UNIVERSITE DE ROUEN-NORMANDIE
Antibiotic resistance is a process that has accelerated worryingly in recent years due to the misuse of antibiotics in human and animal health and the reduction in investment in the research and development of new molecules. The exhaustion of therapeutic options has favored the emergence of resistant or even multi-resistant strains, caused an extension of the duration of hospitalizations and increased the mortality rate linked to bacterial infections. To try to control this phenomenon and coordinate efforts at the international level, the World Health Organization has published a list of priority germs to promote research which aims in particular to identify new molecular targets in several pathogens leading to fatal infections including Pseudomonas aeruginosa. P.aeruginosa is a well-known opportunistic human pathogen responsible for acute and chronic infections whose pathogenesis is largely linked to its ability to adapt to the environment. Remarkably sophisticated in P. aeruginosa, the envelope is a very dynamic compartment whose very finely regulated lipid and protein composition adjusts to the conditions encountered in the external environment to allow the bacteria to adapt its physiology and the permeability of the membranes, and thus counteract the effect of numerous attacks, including in particular those linked to the action of antibiotics or the immune system. For these reasons, the identification of new structural elements significantly involved in its homeostasis and/or its integrity is an avenue of choice to consider potentiating the activity, or developing in the longer term, new anti-Pseudomonas molecules. In this context, the functional characterization of mechanosensitive ion channels and their involvement in the remodeling of the bacterial envelope constitutes a relevant and still unexplored research theme in P. aeruginosa. MechanoSensitive Channels (MSCs) are ubiquitous membrane proteins forming aqueous channels whose mechanical opening allows rapid flows of intra- or extracellular molecules according to their chemical gradient. By converting a physical force into an electrochemical signal, these proteins constitute or are part of mechanosensing systems well known in higher organisms to regulate essential physiological processes, such as hearing, touch, blood pressure in humans or morphogenesis and root orientation in plants. Relatively well studied from a structural and biochemical point of view in the model organism Escherichia coli for their involvement in the response to hypo-osmolarity, their involvement in bacterial physiology and envelope homeostasis, remains highly investigated, although their role in bacterial pathogenicity or the response to antimicrobials is only emerging in recent years through a few cross-sectional or global studies without being the subject of specific in-depth study in bacteria pathogens. Interestingly, P. aeruginosa has 8 putative MSCs (6 in E. coli) of different sizes which generally contain one or more additional protein domains, suggesting their specific involvement in physiological processes.(...)See the rest in the attached document.
Smarter Europe / Research and innovation / Research and innovation activities in public research centres and centres of competence including networking