Document Type
Article
Publication Date
11-2019
DOI
10.3390/ijms20215289
Publication Title
International Journal of Molecular Sciences
Volume
20
Issue
21
Pages
5289 (14 pg.)
Abstract
The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue.
Original Publication Citation
Oludiran, A., Courson, D. S., Stuart, M. D., Radwan, A. R., Poutsma, J. C., Cotten, M. L., & Purcell, E. B. (2019). How oxygen availability affects the antimicrobial efficacy of host defense peptides: Lessons learned from studying the copper-binding peptides piscidins 1 and 3. International Journal of Molecular Sciences, 20(21), 5289. doi:10.3390/ijms20215289
Repository Citation
Oludiran, Adenrele; Courson, David S.; Stuart, Malia D.; Radwan, Anwar R.; Putsma, John C.; Cotten, Myriam L.; and Purcell, Erin B., "How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3" (2019). Chemistry & Biochemistry Faculty Publications. 177.
https://digitalcommons.odu.edu/chemistry_fac_pubs/177
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Chemistry Commons, Molecular Biology Commons
Comments
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.