An increasing number of bacterial pathogens are acquiring multi-drug resistance (MDR) to different classes of antibiotics, with certain types of Gram-negative bacteria, such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, becoming a general health threat. Therefore new drugs are urgently needed to reduce the risk of dangerous and costly infections, and antimicrobial peptides (AMPs) represent a valuable candidate as new antimicrobials. AMPs are an important component of the innate immune system, possessing both antimicrobial and immune-modulatory effects, and are produced among all the living kingdoms. They are small and cationic molecules exerting their activity mainly disrupting bacterial membranes, despite not all of them act via a lytic mechanism of action. Indeed the class of proline-rich peptides (PR-AMPs) has been shown to act intracellularly and their mode of action has been well characterised in Escherichia coli, relying on the inhibition of protein synthesis upon entry into the cell via the membrane protein SbmA.
Our efforts are currently devoted to evaluate the activity of the PR-AMP Bac7 against clinically relevant bacteria, such as those mentioned above, in order to broaden the activity spectrum of the peptide. Moreover we are characterising the mechanism of action of Bac7 against Pseudomonas aeruginosa, showing that the peptide kills this microorganism with a different mode of action with respect to that described for Escherichia coli, and we are exploiting RNAseq analysis to obtain new insights into the mode action of Bac7 against Salmonella typhimurium.