The proline-rich antimicrobial peptide B7-005: low bacterial resistance, safe for human cells and effective in zebrafish embryo bacteraemia model

Proline-rich antimicrobial peptides (PrAMPs) have gained attention due to their antimicrobial properties and low cytotoxicity. B7-005, a small optimized PrAMP, exhibits a broader spectrum of activity than native PrAMPs, due to an antimicrobial mechanism based on inhibiting prokaryotic protein synthesis and destabilizing bacterial membranes. However, the toxicity and the <i>in vivo</i> efficacy of B7-005 remain poorly understood, so <i>in vitro</i> and <i>in vivo</i> microbiology and toxicology experiments were used to assess its suitability as an anti-infective agent. The incidence of resistance towards B7-005 by <i>E. coli</i> was lower than for other PrAMPs and antibiotics; moreover, it maintained antimicrobial activity in the presence of human serum. B7-005 exerted its antimicrobial effect at a much lower concentration than those causing harmful effects on four different cell types, such as membrane permeabilization or non-lytic depolarization of mitochondria. The latter effect may be related to the inhibition of eukaryotic protein synthesis by B7-005 observed <i>in vitro</i>. In a zebrafish embryo model, B7-005 was well tolerated and reduced mortality from pre-existing <i>E. coli</i> bacteraemia. Overall, B7-005 was safe for human cells and effective against systemic infection <i>in vivo</i>, making it a promising lead for developing new antibiotics.