Infections by antibiotic-resistant bacteria are becoming a great risk for human health, leading to an urgent need
for new efficient antibacterial therapies. The short, proline-rich antimicrobial peptides from insects gained a lot of interest
as a potential antibacterial treatment, having a low toxicity profile and being mainly active against Gram-negative bacteria.
To know whether these antimicrobial peptides can be used for the treatment of cerebral infections, the blood-brain
barrier transport characteristics of these peptides were investigated. This study describes the results of the in vivo bloodbrain
barrier experiments in mice, as well as the in vitro metabolic stability in mouse plasma and brain of apidaecin
Api137, oncocin, drosocin and drosocin Pro5Hyp. The four investigated peptides showed a significant influx into the
brain with a Kin ranging between 0.37 and 0.86 µL/g x min and brain distribution volumes of 19.6 to 25.8 µL/g. Only for
drosocin, a significant efflux was determined, with a kout of 0.22 min-1. After entering the brain, oncocin was for approximately
80% trapped in the endothelial cells, while the other peptides reached the brain parenchyma for about 70%. All
peptides were stable in plasma and brain during the experiments, with estimated metabolic half-lives ranging between 47
min and 637 min. We conclude that the investigated short, proline-rich antimicrobial peptides show an influx into the
brain, which make them a promising antibacterial treatment of cerebral infections.
Keywords: Antimicrobial peptides, blood-brain barrier, bio-distribution, cell-penetrating peptides, in vivo, stability, transport.
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