Helicity-directed recognition of bacterial phospholipid via radially amphiphilic antimicrobial peptides
The fundamental differences in phospholipids between bacterial and mammalian cell membranes present remarkable opportunities for antimicrobial design. However, it is challenging to distinguish bacterial anionic phospholipid phosphatidylglycerol (PG) from mammalian anionic phosphatidylserine (PS) with the same net charge. Here, we report a class of radially amphiphilic α helix antimicrobial peptides (RAPs) that can selectively discriminate PG from PS, relying on the helix structure. The representative RAP, L<sub>10</sub>-MMBen, can direct the rearrangement of PG vesicles into a lamellar structure with its helix axis parallel to the PG membrane surface. The helical structure imparts both the thermodynamic and kinetic advantages of L<sub>10</sub>-MMBen/PG assembly, and the hiding of hydrophobic regions in RAPs is crucial for PG recognition. L<sub>10</sub>-MMBen exhibits high selectivity against bacteria depending on PG recognition, showing low in vivo toxicity and significant treatment efficacy in mice infection models. Our study introduces a helicity-direct bacterial phospholipid recognition paradigm for designing highly selective antimicrobial peptides.
Authors
- Yueling Yuan
- Yangbin Liang (ORCID: https://orcid.org/0009-0009-9485-5707)
- Menghua Xiong (ORCID: https://orcid.org/0000-0003-0020-5965)
- Shiyan Xiao (ORCID: https://orcid.org/0000-0003-1159-1224)
- Chengrun Li
- Zhanhui Gan (ORCID: https://orcid.org/0000-0002-9646-5747)
- Yan Bao (ORCID: https://orcid.org/0000-0002-5072-9428)
- Houbing Zhang (ORCID: https://orcid.org/0000-0001-7027-5403)
- Songyin Huang (ORCID: https://orcid.org/0000-0002-9575-044X)
- Yucai Wang (ORCID: https://orcid.org/0000-0001-6046-2934)
- Xue‐Hui Dong (ORCID: https://orcid.org/0000-0002-6395-3103)
- Jingxian Chen (ORCID: https://orcid.org/0009-0003-7920-4857)
- Bingchuan Huang (ORCID: https://orcid.org/0009-0001-5042-1490)
- Bing Yuan (ORCID: https://orcid.org/0000-0001-8418-9274)
- Xinshuang Zhang (ORCID: https://orcid.org/0000-0002-9572-2975)
- Yu Huang (ORCID: https://orcid.org/0000-0002-1936-1987)
- Yuhao Zhang (ORCID: https://orcid.org/0009-0002-8430-1646)
- Pengfei Zhang (ORCID: https://orcid.org/0000-0002-5056-6091)
- Cheng Xu (ORCID: https://orcid.org/0009-0008-2222-735X)
- Shuyi Jia (ORCID: https://orcid.org/0000-0003-1827-4432)
Institutions
- University of Science and Technology of China (CN)
- Sun Yat-sen University (CN)
- Sun Yat-sen Memorial Hospital (CN)
- Hefei National Center for Physical Sciences at Nanoscale (CN)
- Songshan Lake Materials Laboratory (CN)
- South China University of Technology (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2024-08-30
- DOI
- https://doi.org/10.1126/sciadv.adn9435
- Citations
- 41
- Primary Topic
- Antimicrobial Peptides and Activities
- Type
- article
- Field-Weighted Citation Impact
- 14.13
Funders
- National Natural Science Foundation of China
- Guangzhou Municipal Science and Technology Bureau
- Basic and Applied Basic Research Foundation of Guangdong Province