Abstract：
: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.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Koufos E,Chang EH,Rasti ES,Krueger E,Brown ACdoi
10.1021/acs.biochem.6b00430subject
Has Abstractpub_date
2016-08-30 00:00:00pages
4787-97issue
34eissn
0006-2960issn
1520-4995journal_volume
55pub_type
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