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Antibiotics 2014, 3(4), 617-631; doi:10.3390/antibiotics3040617

Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes

1
Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germany
2
Interfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany
3
Department of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA
*
Author to whom correspondence should be addressed.
Received: 23 September 2014 / Revised: 30 October 2014 / Accepted: 31 October 2014 / Published: 14 November 2014
(This article belongs to the Special Issue Antimicrobial Peptides)
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Abstract

θ-Defensins are cyclic antimicrobial peptides expressed in leukocytes of Old world monkeys. To get insight into their antibacterial mode of action, we studied the activity of RTDs (rhesus macaque θ-defensins) against staphylococci. We found that in contrast to other defensins, RTDs do not interfere with peptidoglycan biosynthesis, but rather induce bacterial lysis in staphylococci by interaction with the bacterial membrane and/or release of cell wall lytic enzymes. Potassium efflux experiments and membrane potential measurements revealed that the membrane impairment by RTDs strongly depends on the energization of the membrane. In addition, RTD treatment caused the release of Atl-derived cell wall lytic enzymes probably by interaction with membrane-bound lipoteichoic acid. Thus, the premature and uncontrolled activity of these enzymes contributes strongly to the overall killing by θ-defensins. Interestingly, a similar mode of action has been described for Pep5, an antimicrobial peptide of bacterial origin. View Full-Text
Keywords: antimicrobial peptides; host defense peptides; defensins; antibiotics; mode of action antimicrobial peptides; host defense peptides; defensins; antibiotics; mode of action
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wilmes, M.; Stockem, M.; Bierbaum, G.; Schlag, M.; Götz, F.; Tran, D.Q.; Schaal, J.B.; Ouellette, A.J.; Selsted, M.E.; Sahl, H.-G. Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes. Antibiotics 2014, 3, 617-631.

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