Killing of Staphylococci by θ-Defensins Involves Membrane Impairment and Activation of Autolytic Enzymes
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
Affiliations
Miriam Wilmes
Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germany
Marina Stockem
Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germany
Gabriele Bierbaum
Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germany
Martin Schlag
Interfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany
Friedrich Götz
Interfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany
Dat Q. Tran
Department of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA
Justin B. Schaal
Department of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA
André J. Ouellette
Department of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA
Michael E. Selsted
Department of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA
Hans-Georg Sahl
Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germany
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.
