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首页> 外文期刊>Biochemistry >Use of a Cholesterol Recognition Amino Acid Consensus Peptide To Inhibit Binding of a Bacterial Toxin to Cholesterol
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Use of a Cholesterol Recognition Amino Acid Consensus Peptide To Inhibit Binding of a Bacterial Toxin to Cholesterol

机译：胆固醇识别氨基酸共识肽的使用，以抑制细菌毒素与胆固醇的结合

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摘要

Recognition of and binding to cholesterol on the host cell membrane is an initial step in the mechanism of numerous pathogens, including viruses, bacteria, and bacterial toxins; however, a viable method of inhibiting this interaction has not yet been uncovered. Here, we describe the mechanism by which a cholesterol recognition amino acid consensus peptide interacts with cholesterol and inhibits the activity of a cholesterol-binding bacterial leukotoxin (LtxA). Using a series of biophysical techniques, we have shown that the peptide recognizes the hydroxyl group of cholesterol with nanomolar affinity and does not disrupt membrane packing, suggesting that it sits primarily near the membrane surface. As a result, LtxA is unable to bind to cholesterol or subsequently become internalized in host cells. Additionally, because cholesterol is not being removed from the cell membrane, the peptide-treated target cells remain viable over extended periods of time. We have demonstrated the use of this peptide in the inhibition of toxin activity for an antivirulence approach to the treatment of bacterial disease, and we anticipate that this approach might have broad utility in the inhibition of viral and bacterial pathogenesis.
机译：识别并结合宿主细胞膜上的胆固醇是众多病原体（包括病毒，细菌和细菌毒素）机制中的第一步;然而，尚未发现抑制这种相互作用的可行方法。在这里，我们描述了胆固醇识别氨基酸共有肽与胆固醇相互作用并抑制胆固醇结合细菌白细胞毒素（LtxA）活性的机制。使用一系列的生物物理技术，我们发现该肽以纳摩尔亲和力识别胆固醇的羟基，并且不会破坏膜的堆积，表明它主要位于膜表面附近。结果，LtxA无法结合胆固醇或随后被宿主细胞内化。另外，由于未从细胞膜上除去胆固醇，因此经肽处理的靶细胞在延长的时间内仍保持活力。我们已经证明了这种肽在抑制毒素活性方面的用途，可用于治疗细菌性疾病的抗毒方法，并且我们预计该方法在抑制病毒和细菌发病机理中可能具有广泛的用途。

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