Guiding antibiotics towards their target using bacteriophage proteins

Xinghong Zhao (), Xinyi Zhong, Shinong Yang, Jiarong Deng, Kai Deng, Zhengqun Huang, Yuanfeng Li, Zhongqiong Yin (), Yong Liu (), Jakob H. Viel and Hongping Wan ()
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Xinghong Zhao: Sichuan Agricultural University
Xinyi Zhong: Sichuan Agricultural University
Shinong Yang: Sichuan Agricultural University
Jiarong Deng: Sichuan Agricultural University
Kai Deng: Sichuan Agricultural University
Zhengqun Huang: Sichuan Agricultural University
Yuanfeng Li: The First Affiliated Hospital of Wenzhou Medical University
Zhongqiong Yin: Sichuan Agricultural University
Yong Liu: University of Chinese Academy of Sciences
Jakob H. Viel: University of Groningen
Hongping Wan: Sichuan Agricultural University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.

Date: 2024
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DOI: 10.1038/s41467-024-49603-4

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