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

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...

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Main Authors: Miriam Wilmes, Marina Stockem, Gabriele Bierbaum, Martin Schlag, Friedrich Götz, Dat Q. Tran, Justin B. Schaal, André J. Ouellette, Michael E. Selsted, Hans-Georg Sahl
Format: Article
Language:English
Published: MDPI AG 2014-11-01
Series:Antibiotics
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Online Access:http://www.mdpi.com/2079-6382/3/4/617
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author Miriam Wilmes
Marina Stockem
Gabriele Bierbaum
Martin Schlag
Friedrich Götz
Dat Q. Tran
Justin B. Schaal
André J. Ouellette
Michael E. Selsted
Hans-Georg Sahl
author_facet Miriam Wilmes
Marina Stockem
Gabriele Bierbaum
Martin Schlag
Friedrich Götz
Dat Q. Tran
Justin B. Schaal
André J. Ouellette
Michael E. Selsted
Hans-Georg Sahl
author_sort Miriam Wilmes
collection DOAJ
description 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.
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spelling doaj.art-7b14842637b245e8880e496eb528f04b2022-12-21T23:43:42ZengMDPI AGAntibiotics2079-63822014-11-013461763110.3390/antibiotics3040617antibiotics3040617Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic EnzymesMiriam Wilmes0Marina Stockem1Gabriele Bierbaum2Martin Schlag3Friedrich Götz4Dat Q. Tran5Justin B. Schaal6André J. Ouellette7Michael E. Selsted8Hans-Georg Sahl9Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, GermanyInstitute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, GermanyInstitute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, GermanyInterfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, 72076 Tübingen, GermanyInterfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, 72076 Tübingen, GermanyDepartment of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USADepartment of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USADepartment of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USADepartment of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USAInstitute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germanyθ-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.http://www.mdpi.com/2079-6382/3/4/617antimicrobial peptideshost defense peptidesdefensinsantibioticsmode of action
spellingShingle Miriam Wilmes
Marina Stockem
Gabriele Bierbaum
Martin Schlag
Friedrich Götz
Dat Q. Tran
Justin B. Schaal
André J. Ouellette
Michael E. Selsted
Hans-Georg Sahl
Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
Antibiotics
antimicrobial peptides
host defense peptides
defensins
antibiotics
mode of action
title Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
title_full Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
title_fullStr Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
title_full_unstemmed Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
title_short Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
title_sort killing of staphylococci by θ defensins involves membrane impairment and activation of autolytic enzymes
topic antimicrobial peptides
host defense peptides
defensins
antibiotics
mode of action
url http://www.mdpi.com/2079-6382/3/4/617
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