The antimicrobial peptide Temporin-L induces vesicle formation and reduces the virulence in S. aureus

The evolution of methicillin-resistant Staphylococcus aureus (MRSA) has required the development of new antimicrobial agents and new approaches to prevent and overcome drug resistance. AntiMicrobial Peptides (AMPs) represent promising alternatives due to their rapid bactericidal activity and their broad-spectrum of action against a wide range of microorganisms. The amphibian Temporins constitute a well-known family of AMPs with high antibacterial properties against both Gram-positive and Gram-negative bacteria. In this paper, we evaluated the in vivo effect of Temp-L on S. aureus performing morphological studies using Transmission Electron Microscopy (TEM) that revealed the occurrence of protrusions from the cell surface. The formation of vesicle-like structure was confirmed by Dynamic Light Scattering (DLS). The global effect of Temp-L on Staphylococcus aureus (S. aureus) was deeply investigated by differential proteomics leading to the identification of up-regulated proteins involved in the synthesis of the cell membrane and fatty acids, and down-regulated virulence factors. GC-MS analysis suggested a possible protective response mechanism implemented by the bacterium after treatment with Temp-L, as the synthesis of fatty acids was increased. Adhesion and invasion assays on eukaryotic cells confirmed a reduced virulence of S. aureus following treatment with Temp-L. These results suggested the targeting of virulence factors as novel strategy to replace traditional antimicrobial agents that can be used to treat infections, especially infections caused by the resistant pathogen S. aureus. •Antibiotic resistance is increasing worldwide, and new antimicrobial molecules are needed to overcome the treatment of severe Staphylococcus aureus infections.•Temporin-L is able to induce ultrastructural changes in Staphylococcus aureus by forming vesicles on the cell surface as a defence mechanism.•Temporin-L decreases the virulence of Staphylococcus aureus due to down-regulation of proteins involved in virulence, suggesting that targeting virulence factors is a new alternative to conventional antibiotics.