Receptor-Based Peptides for Inhibition of Leukotoxin Activity.
Receptor-Based Peptides for Inhibition of Leukotoxin Activity.
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DOI：
10.1021/acsinfecdis.7b00230
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发表时间：
2018-07-13
影响因子：
5.3
通讯作者：
Brown AC
中科院分区：
文献类型：
--
作者：
Krueger E;Hayes S;Chang EH;Yutuc S;Brown AC
The Gram-negative bacterium Aggregatibacter actinomycetemcomitans, commonly associated with localized aggressive periodontitis (LAP), secretes an RTX (repeats-in-toxin) protein leukotoxin (LtxA) that targets human white blood cells, an interaction that is driven by its recognition of the lymphocyte function-associated antigen-1 (LFA-1) integrin. In this study, we report on the inhibition of LtxA-LFA-1 binding as an antivirulence strategy to inhibit LtxA-mediated cytotoxicity. Specifically, we designed and synthesized peptides corresponding to the reported LtxA binding domain on LFA-1 and characterized their capability to inhibit LtxA binding to LFA-1 and subsequent cytotoxic activity in human immune cells. We found that several of these peptides, corresponding to sequential β-strands in the LtxA-binding domain of LFA-1, inhibit LtxA activity, demonstrating the effectiveness of this approach. Further investigations into the mechanism by which these peptides inhibit LtxA binding to LFA-1 reveal a correlation between toxin-peptide affinity and LtxA-mediated cytotoxicity, leading to a diminished association between LtxA and LFA-1 on the cell membrane. Our results demonstrate the possibility of using target-based peptides to inhibit LtxA activity, and we expect that a similar approach could be used to hinder the activity of other RTX toxins.
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影响因子：
3.7
作者：
Balashova N;Dhingra A;Boesze-Battaglia K;Lally ET
通讯作者：
Lally ET
DOI：
10.1016/j.bbapap.2007.01.002
发表时间：
2007-03-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Fong, K. P.;Tang, H. -Y.;Lally, E. T.
通讯作者：
Lally, E. T.