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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2014-11-01
|
Series: | Antibiotics |
Subjects: | |
Online Access: | http://www.mdpi.com/2079-6382/3/4/617 |
_version_ | 1818332571193311232 |
---|---|
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. |
first_indexed | 2024-12-13T13:37:51Z |
format | Article |
id | doaj.art-7b14842637b245e8880e496eb528f04b |
institution | Directory Open Access Journal |
issn | 2079-6382 |
language | English |
last_indexed | 2024-12-13T13:37:51Z |
publishDate | 2014-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Antibiotics |
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 |
work_keys_str_mv | AT miriamwilmes killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT marinastockem killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT gabrielebierbaum killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT martinschlag killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT friedrichgotz killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT datqtran killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT justinbschaal killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT andrejouellette killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT michaeleselsted killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes AT hansgeorgsahl killingofstaphylococcibythdefensinsinvolvesmembraneimpairmentandactivationofautolyticenzymes |