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

Antibiotics

Miriam Wilmes²  Marina Stockem²  Gabriele Bierbaum²  Martin Schlag¹  Friedrich Götz¹  Dat Q. Tran³  Justin B. Schaal³  André J. Ouellette³  Michael E. Selsted³  Hans-Georg Sahl² 

[1] Interfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, 72076 Tübingen, Germany; E-Mails:;Institute of Medical Microbiology, Immunology and Parasitology, University of Bonn, 53105 Bonn, Germany; E-Mails:;Department of Pathology and Laboratory Medicine, USC Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9601, USA; E-Mails:

关键词: antimicrobial peptides;    host defense peptides;    defensins;    antibiotics;    mode of action;   

DOI  :  10.3390/antibiotics3040617

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.