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Article

How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3

1
Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA 23529, USA
2
Biology Department, Palomar College, San Marcos, CA 92069, USA
3
Department of Chemistry, College of William and Mary, Williamsburg, VA 23185, USA
4
Department of Applied Science, College of William and Mary, Williamsburg, VA 23185, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5289; https://doi.org/10.3390/ijms20215289
Received: 27 September 2019 / Revised: 21 October 2019 / Accepted: 22 October 2019 / Published: 24 October 2019
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
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. View Full-Text
Keywords: host defense peptides; membrane activity; copper; piscidins; Clostridioides difficile host defense peptides; membrane activity; copper; piscidins; Clostridioides difficile
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MDPI and ACS Style

Oludiran, A.; Courson, D.S.; Stuart, M.D.; Radwan, A.R.; Poutsma, J.C.; Cotten, M.L.; Purcell, E.B. How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3. Int. J. Mol. Sci. 2019, 20, 5289. https://doi.org/10.3390/ijms20215289

AMA Style

Oludiran A, Courson DS, Stuart MD, Radwan AR, Poutsma JC, Cotten ML, Purcell EB. 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. 2019; 20(21):5289. https://doi.org/10.3390/ijms20215289

Chicago/Turabian Style

Oludiran, Adenrele, David S. Courson, Malia D. Stuart, Anwar R. Radwan, John C. Poutsma, Myriam L. Cotten, and Erin B. Purcell. 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, no. 21: 5289. https://doi.org/10.3390/ijms20215289

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