Antimicrobial peptides from the microbiome as modulators of bacterial virulence

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The gut microbiome has been intensively studied lately because of its fundamental role in human health. However, the molecular dialogue between the bacteria from the microbiome is still poorly understood. My research focus on understanding this dialogue in a cooperative or a competitive bacterial relationship. The bacteria from the microbiome are producing antimicrobial peptides (AMPs), which have an important role in regulating the microbial community. The aim of this proposal is to determine if AMPs produced by the microbiome can modulate the expression and secretion of proteins involved in virulence and resistance in V. cholerae. Therefore, our specific objectives are to: i) Identify and select bacteria from the microbiome that produce AMP(s) active against V. cholerae. Two approaches will be considered. A random approach consisting of the screening of a bacterial collection from the microbiome for their anti-Vibrio activity, followed by an identification of the producer and a purification of the AMPs. The second approach consist on the selection of the AMPs produced by bacteria from the microbiome based on the available literature, eventually followed by a cloning and purification.ii) Determine how the AMPs from the microbiome affect the expression and secretion of proteins from V. cholerae. A global proteomic approach will be performed to identify the protein differentially expressed in presence of AMPs. A construction of the mutants of the genes coding for the identified effectors will follow for the identification of the role of the effector proteins in antimicrobial peptide resistance and in virulence using animal models.iii) Identify the risk of developing a resistance to the AMPs from the microbiome, by cultivating different intestinal pathogens with low concentration of the AMPs from the microbiome.This work will greatly improve our knowledge of bacteria-bacteria communication in the gut at the molecular level. The novelty resides in considering AMPs as molecules that can subvert the signalling pathways of the neighbouring bacteria, including pathogens, therefore modulating their ability to adapt to their environment.