Our lab is part of the French Phage.fr network
The Tol system has been extensively studied, mostly in E. coli, but numerous questions remain on the assembly, the functioning and the biological role of the complex. We recently chose to work on Vibrio cholerae as a model organism in order to open new perspectives in the understanding of the Tol-Pal system. The Tol-Pal system is conserved in Vibrioneceae and displays genomic and phenotypic characteristics that may be useful for deciphering the structure-function of this complex.
Vibrio cholerae is a bacterial natural inhabitant of estuarine, and the causative agent of epidemic disease cholera. While more than 200 O-antigen serogroups have been described, only two have been reported to cause the pandemic disease cholera: the O1 and O139 serotypes, due to the production of two essential virulence factors: the Toxin Co-regulated Pilus (TCP) and the Cholera Toxin (CT). Interestingly, the ctxAB genes encoding the enterotoxin CT are not carried by the core genome of the bacterium, but can be acquired after infection by a lysogenic bacteriophage known as CTXΦ. Once infected, the bacterium produces CT, and assembles new phage particles (carrying the ctxAB genes) that will be secreted in the environment, and may convert non-pathogenic V. cholerae cells to pathogenicity.
As for coliphages Ff (including f1φ, fdφ, and M13φ) infecting E. coli, CTX import across the V. cholerae periplasm requires the Tol-Pal system. The series of molecular events during phage import is still unclear but requires direct binding between the G3P protein located at the tip of the phage and the TolA protein in the periplasm.
In this project, we aim to:
Map the interaction network between the CTX phage and the Tol-Pal system and identify the determinants of phage-host specificity.
Determine the series of molecular events involved during phage transport across the periplasm.
Study the regulatory mechanisms operating on the tol-pal cluster in response to environmental signals.
The expected results will shed new light on the mechanism of phage-dependent pathogenic conversion in bacteria, and open new perspectives in the engineering of hybrid phages designed to deliver molecules of interest in bacteria.