This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xiong, Y. Q.
Right arrow Articles by Bayer, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiong, Y. Q.
Right arrow Articles by Bayer, A. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2005, p. 3114-3121, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3114-3121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Functional Interrelationships between Cell Membrane and Cell Wall in Antimicrobial Peptide-Mediated Killing of Staphylococcus aureus

Yan Q. Xiong,1,2,3*,{dagger} Kasturi Mukhopadhyay, Michael R. Yeaman,1,2,3 Jill Adler-Moore,4 and Arnold S. Bayer1,2,3

The LA Biomedical Research Institute at Harbor—UCLA, Torrance, California,1 Department of Medicine, Harbor—UCLA Medical Center, Torrance, California,2 The David Geffen School of Medicine at UCLA, Los Angeles, California,3 Department of Microbiology, California Polytechnical State University at Pomona, Pomona, California4

Received 7 January 2005/ Returned for modification 22 March 2005/ Accepted 19 April 2005

Perturbation of the Staphylococcus aureus cytoplasmic membrane (CM) is felt to play a key role in the microbicidal mechanism of many antimicrobial peptides (APs). However, it is not established whether membrane permeabilization (MP) alone is sufficient to kill susceptible staphylococci or if the cell wall (CW) and/or intracellular targets contribute to AP-induced lethality. We hypothesized that the relationships between MP and killing may differ for distinct APs. In this study, we investigated the association between AP-induced MP and lethality in S. aureus whole cells versus CW-free protoplasts, and in comparison to the MP of liposomes modeled after whole CMs in terms of phospholipid composition, fluidity and charge. Four APs with different structure-activity relationships were examined: thrombin-induced platelet microbicidal protein 1 (tPMP-1), human neutrophil protein 1 (hNP-1), gramicidin D, and polymyxin B. MP was quantified fluorometrically by calcein release. All APs tested, except polymyxin B, caused concentration-dependent MP and killing of whole cells, but not of protoplasts. The reduced AP susceptibility of protoplasts was associated with increased cardiolipin and lysyl-phosphatidylglycerol content and reduced fluidity of their CMs. However, liposomal MP induced by tPMP-1, hNP-1, and gramicidin D paralleled that of whole cells. Collectively, these results indicate that (i) structurally distinct APs likely exert their staphylocidal effects by differing mechanisms, (ii) MP is not the sole event leading to AP-induced staphylocidal activity, (iii) a complex interrelationship exists between the CM and CW in AP-induced killing, and (iv) liposomes modeled upon whole cell or protoplast CMs can recapitulate the respective susceptibilities to killing by distinct APs.

* Corresponding author. Mailing address: LA Biomedical Research Institute at Harbor-UCLA St. John's Cardiovascular Research Center, RB-2, 1124 West Carson Street, Torrance, CA 90502. Phone: (310) 222-3545. Fax: (310) 782-2016. E-mail: yxiong{at}ucla.edu.

{dagger} Y.Q.X. and K.M. contributed equally to this work.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3114-3121, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3114-3121.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jean-Francois, F., Desbat, B., Dufourc, E. J. (2009). Selectivity of cateslytin for fungi: the role of acidic lipid-ergosterol membrane fluidity in antimicrobial action. FASEB J. 23: 3692-3701 [Abstract] [Full Text]  
  • Mishra, N. N., Yang, S.-J., Sawa, A., Rubio, A., Nast, C. C., Yeaman, M. R., Bayer, A. S. (2009). Analysis of Cell Membrane Characteristics of In Vitro-Selected Daptomycin-Resistant Strains of Methicillin-Resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 53: 2312-2318 [Abstract] [Full Text]  
  • Camargo, I. L. B. d. C., Neoh, H.-M., Cui, L., Hiramatsu, K. (2008). Serial Daptomycin Selection Generates Daptomycin-Nonsusceptible Staphylococcus aureus Strains with a Heterogeneous Vancomycin-Intermediate Phenotype. Antimicrob. Agents Chemother. 52: 4289-4299 [Abstract] [Full Text]  
  • Do, T. Q., Moshkani, S., Castillo, P., Anunta, S., Pogosyan, A., Cheung, A., Marbois, B., Faull, K. F., Ernst, W., Chiang, S. M., Fujii, G., Clarke, C. F., Foster, K., Porter, E. (2008). Lipids Including Cholesteryl Linoleate and Cholesteryl Arachidonate Contribute to the Inherent Antibacterial Activity of Human Nasal Fluid. J. Immunol. 181: 4177-4187 [Abstract] [Full Text]  
  • Jones, T., Yeaman, M. R., Sakoulas, G., Yang, S.-J., Proctor, R. A., Sahl, H.-G., Schrenzel, J., Xiong, Y. Q., Bayer, A. S. (2008). Failures in Clinical Treatment of Staphylococcus aureus Infection with Daptomycin Are Associated with Alterations in Surface Charge, Membrane Phospholipid Asymmetry, and Drug Binding. Antimicrob. Agents Chemother. 52: 269-278 [Abstract] [Full Text]  
  • Mukhopadhyay, K., Whitmire, W., Xiong, Y. Q., Molden, J., Jones, T., Peschel, A., Staubitz, P., Adler-Moore, J., McNamara, P. J., Proctor, R. A., Yeaman, M. R., Bayer, A. S. (2007). In vitro susceptibility of Staphylococcus aureus to thrombin-induced platelet microbicidal protein-1 (tPMP-1) is influenced by cell membrane phospholipid composition and asymmetry. Microbiology 153: 1187-1197 [Abstract] [Full Text]  
  • Xiong, Y. Q., Bayer, A. S., Elazegui, L., Yeaman, M. R. (2006). A Synthetic Congener Modeled on a Microbicidal Domain of Thrombin- Induced Platelet Microbicidal Protein 1 Recapitulates Staphylocidal Mechanisms of the Native Molecule. Antimicrob. Agents Chemother. 50: 3786-3792 [Abstract] [Full Text]  
  • Bayer, A. S., Kupferwasser, L. I., Brown, M. H., Skurray, R. A., Grkovic, S., Jones, T., Mukhopadhay, K., Yeaman, M. R. (2006). Low-Level Resistance of Staphylococcus aureus to Thrombin-Induced Platelet Microbicidal Protein 1 In Vitro Associated with qacA Gene Carriage Is Independent of Multidrug Efflux Pump Activity.. Antimicrob. Agents Chemother. 50: 2448-2454 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»