Proteomic analysis of murine macrophages mitochondria and lysosomes reveal Cathepsin D as a potential broad-spectrum antimicrobial protein.

Qihuan Fu, Jiangbei Yuan, Liting Wang, Haiying Ran, Fei Li, Fang Liu, Junying Zhang, Wenhu Liu, Wei Huang, Yi Huang, Xuefeng Xia

Journal of proteomics 2020 Jul 15

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Bacterial resistance to antibiotics has become increasingly widespread, posing a serious threat to human life and health. Macrophages in the host's natural immune system can directly destroy most of bacteria. Therefore, exploring the function of macrophages' mitochondria and lysosomes in killing bacteria might help us overcome the problem of bacterial resistance. We used mass spectrometry to analyze the dynamic expression landscape of mitochondrial and lysosomal proteins in macrophages upon infection with Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. We discovered that Cathepsin D (Ctsd) is up-regulated at the protein level during infection by all five bacteria. Ctsd inhibitor and knockout experiments confirmed that Ctsd is a potential broad-spectrum antibacterial protein. Ctsd should be investigated further as a potential drug target for new antibacterial treatments. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Qihuan Fu, Jiangbei Yuan, Liting Wang, Haiying Ran, Fei Li, Fang Liu, Junying Zhang, Wenhu Liu, Wei Huang, Yi Huang, Xuefeng Xia. Proteomic analysis of murine macrophages mitochondria and lysosomes reveal Cathepsin D as a potential broad-spectrum antimicrobial protein. Journal of proteomics. 2020 Jul 15;223:103821