A novel Omp25-binding peptide screened by phage display can inhibit Brucella abortus 2308 infection in vitro and in vivo

通过噬菌体展示筛选的新型 Omp25 结合肽可在体内和体外抑制布鲁氏菌 2308 感染

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作者:Junbo Zhang, Fei Guo, Xiaoqiang Huang, Chuangfu Chen, Ruitian Liu, Hui Zhang, Yuanzhi Wang, Shuanghong Yin, Zhiqiang Li

Abstract

Brucellosis is a globally distributed zoonotic disease affecting animals and humans, and current antibiotic and vaccine strategies are not optimal. The surface-exposed protein Omp25 is involved in Brucella virulence and plays an important role in Brucella pathogenesis during infection, suggesting that Omp25 could be a useful target for selecting potential therapeutic molecules to inhibit Brucella pathogenesis. In this study, we identified, we believe for the first time, peptides that bind specifically to the Omp25 protein of pathogens, using a phage panning technique, After four rounds of panning, 42 plaques of eluted phages were subjected to pyrosequencing. Four phage clones that bound better than the other clones were selected following confirmation by ELISA and affinity constant determination. The peptides selected could significantly inhibit Brucella abortus 2308 (S2308) internalization and intracellular growth in RAW264.7 macrophages, and significantly induce secretion of TNF-α and IL-12 in peptide- and S2308-treated cells. Any observed peptide (OP11, OP27, OP35 or OP40) could significantly inhibit S2308 infection in BALB/c mice. Moreover, the peptide OP11 was the best candidate peptide for inhibiting S2308 infection in vitro and in vivo. These results suggest that peptide OP11 has potential for exploitation as a peptide drug in resisting S2308 infection.

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