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Antimicrobial Peptides: Successes, Challenges and Unanswered Questions

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Abstract

Multidrug antibiotic resistance is an increasingly serious public health problem worldwide. Thus, there is a significant and urgent need for the development of new classes of antibiotics that do not induce resistance. To develop such antimicrobial compounds, we must look toward agents with novel mechanisms of action. Membrane-permeabilizing antimicrobial peptides (AMPs) are good candidates because they act without high specificity toward a protein target, which reduces the likelihood of induced resistance. Understanding the mechanism of membrane permeabilization is crucial for the development of AMPs into useful antimicrobial agents. Various models, some phenomenological and others more quantitative or semimolecular, have been proposed to explain the action of AMPs. While these models explain many aspects of AMP action, none of the models captures all of the experimental observations, and significant questions remain unanswered. Here, we discuss the state of the field and pose some questions that, if answered, could speed the discovery of clinically useful peptide antibiotics.

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Acknowledgements

This work was supported by NIH grants GM060000, GM068619 and GM095930. We dedicate this review to our advisor Stephen H. White, in whose laboratory we completed our first AMP research projects.

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Authors and Affiliations

  1. Department of Biochemistry, Tulane University Health Sciences Center, New Orleans, LA, 70112, USA

    William C. Wimley

  2. Department of Materials Science and Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA

    Kalina Hristova

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  1. William C. Wimley
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  2. Kalina Hristova
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Correspondence to William C. Wimley.

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Wimley, W.C., Hristova, K. Antimicrobial Peptides: Successes, Challenges and Unanswered Questions. J Membrane Biol 239, 27–34 (2011). https://doi.org/10.1007/s00232-011-9343-0

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  • DOI: https://doi.org/10.1007/s00232-011-9343-0

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