I am Mattéo Gérard, I arrived in the ProCeD team of Micalis on the 1st of December 2023. I started a thesis supervised by Rut Carballido-López, during which I will study interactions between two histidine kinases (HK) GacS and RetS involved in virulence modulation in Pseudomonas aeruginosa.
This Gram-negative bacterium is responsible for healthcare-associated infections, particularly in cystic fibrosis patients, the immunocompromised and burn victims. Some strains are resistant to numerous antibiotics, making them difficult to eliminate from infections. This is why P. aeruginosa has been classified by the World Health Organization (WHO) as a priority in the search for new antibiotics (ESKAPE).
Within the bacterial kingdom, the most widespread signal transduction mechanism enabling bacteria to adapt to their environment is the two-component system, which is generally composed of a transmembrane histidine kinase (HK) and a response regulator (RR). The HK is capable of autophosphorylating in response to a stimulus of its own, and transfers its phosphate to the RR, regulating the transcription of target genes.
The two-component GacS(HK)/GacA(RR) system is key in the regulation of virulence and biofilm genes in P. aeruginosa, activation of which induces a “biofilm” phenotype with the synthesis of exopolysaccharides and extracellular DNA matrix. Conversely, when RetS (HK) interacts with GacS (HK), it prevents its auto-phosphorylation and blocks the mechanism, resulting in a virulent phenotype with the production of a cytotoxic Type III Secretion System (T3SS).
The aim of my thesis is to characterize where, when, and how molecular events involving GacS and RetS occur in the cell, using high-resolution fluorescence microscopy.
