Insect-derived short proline-rich and murine cathelicidin-related antimicrobial peptides act synergistically on Gram-negative bacteria in vitro

Organisms express a set of antimicrobial peptides (AMP) to protect the host against invading microbes by targeting their membranes or intracellular structures. Structurally optimized proline-rich AMPs (PrAMPs) are substantially more efficient in murine infection models than previously assumed from in vitro activities. Thus, we hypothesized that PrAMPs act synergistically with lytic AMPs intrinsically produced in hosts in response to an infection. Synergistic effects between lytic murine cathelicidin-related AMP (CRAMP) and apidaecin- and oncocin-derivatives were studied in chequerboard assays. Evaluation of fractional inhibitory concentration indices revealed synergies against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. CRAMP synergistically enhances the activity of proline-rich AMPs, which will allow evaluating their therapeutic potential more precisely in vitro.