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<p>Infection caused by neuroinvasive <i>Borrelia</i> often manifests long-term CNS disorders and is difficult to treat as most antibiotics fail to attain an effective concentration within the brain or cannot kill the persister forms of <i>Borrelia</i> (cysts and round bodies). Thus, this study focused on developing antimicrobial cyclic peptides (AMPs) from a combinatorial phage display library that target phosphatidylcholine of the borrelial cell membrane. Isolated cyclic peptides with anti-<i>Borrelia</i> properties were then fused with the CNS homing peptide developed in this study (designated as O-BBB) to facilitate AMP transport across the blood-brain barrier. Among all O-BBB fused AMPs, Bor-18 had half maximal effective concentration (EC<sub>50</sub>) 0.83 µM when tested against spirochetal <i>Borrelia</i>. Bor-16, Bor-18, and Bor-26 inhibited the cystic form with EC<sub>50</sub> 0.83 µM, while Bor-11 had EC<sub>50</sub> 0.41 µM. Within an hour, all four peptides caused a permeability breach in the borrelial cell membrane, causing depolarization of the membrane. Bor peptides did not inhibit eukaryotic cell metabolism or proliferation, nor did they cause erythrocyte lysis. Peptides were stable in serum, could cross the BBB in-vitro, and remained effective against <i>Borrelia</i>. Cyclic AMPs fused with a CNS homing moiety, the Bor peptides, deserve further investigation for their potential use in neuroborreliosis therapy.</p>

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Antimicrobial cyclic peptides effectively inhibit multiple forms of Borrelia and cross the blood-brain barrier model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月20日

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  • Evelína Mochnáčová,
  • Katarína Bhide,
  • Katarína Kucková,
  • Jana Jozefiaková,
  • Tomáš Maľarik,
  • Mangesh Bhide

摘要

Infection caused by neuroinvasive Borrelia often manifests long-term CNS disorders and is difficult to treat as most antibiotics fail to attain an effective concentration within the brain or cannot kill the persister forms of Borrelia (cysts and round bodies). Thus, this study focused on developing antimicrobial cyclic peptides (AMPs) from a combinatorial phage display library that target phosphatidylcholine of the borrelial cell membrane. Isolated cyclic peptides with anti-Borrelia properties were then fused with the CNS homing peptide developed in this study (designated as O-BBB) to facilitate AMP transport across the blood-brain barrier. Among all O-BBB fused AMPs, Bor-18 had half maximal effective concentration (EC50) 0.83 µM when tested against spirochetal Borrelia. Bor-16, Bor-18, and Bor-26 inhibited the cystic form with EC50 0.83 µM, while Bor-11 had EC50 0.41 µM. Within an hour, all four peptides caused a permeability breach in the borrelial cell membrane, causing depolarization of the membrane. Bor peptides did not inhibit eukaryotic cell metabolism or proliferation, nor did they cause erythrocyte lysis. Peptides were stable in serum, could cross the BBB in-vitro, and remained effective against Borrelia. Cyclic AMPs fused with a CNS homing moiety, the Bor peptides, deserve further investigation for their potential use in neuroborreliosis therapy.