Synthetic hydrophobic peptides derived from MgtR weaken Salmonella pathogenicity and work with a different mode of action than endogenously produced peptides.

Due to the antibiotic resistance crisis, novel therapeutic strategies need to be developed against bacterial pathogens. Hydrophobic bacterial peptides (small proteins under 50 amino acids) have emerged as regulatory molecules that can interact with bacterial membrane proteins to modulate their activity and/or stability. Among them, the Salmonella MgtR peptide promotes the degradation of MgtC, a virulence factor involved in Salmonella intramacrophage replication, thus providing the basis for an antivirulence strategy.

Endogenous and Exogenous KdpF Peptide Increases Susceptibility of BCG to Nitrosative Stress and Reduces Intramacrophage Replication.

Emerging antibiotic resistance in pathogenic bacteria like sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species.

Use of the Salmonella MgtR peptide as an antagonist of the Mycobacterium MgtC virulence factor.

Background: The MgtC virulence factor has been proposed as an attractive target for antivirulence strategies because it is shared by several important bacterial pathogens, including Salmonella enterica and Mycobacterium tuberculosis (Mtb).

Aim: A natural antagonistic peptide, MgtR, which interacts with MgtC and modulates its stability, has been identified in Salmonella, and we investigated its efficiency to target MgtC in another pathogen.

Materials & Methods: We evaluated the interaction between Salmonella MgtR peptide and the Mtb MgtC protein using an in vivo bacterial two-hybrid system and we addressed the effect of exogenously added synthetic MgtR and endogenously expressed peptide.