TY - JOUR
T1 - Antimicrobial peptides
T2 - Successes, challenges and unanswered questions
AU - Wimley, William C.
AU - Hristova, Kalina
N1 - Funding Information:
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.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Antimicrobial peptide
KW - Bacteria
KW - Carpet model
KW - Permeabilization
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U2 - 10.1007/s00232-011-9343-0
DO - 10.1007/s00232-011-9343-0
M3 - Article
C2 - 21225255
AN - SCOPUS:79955669580
SN - 0022-2631
VL - 239
SP - 27
EP - 34
JO - Journal of Membrane Biology
JF - Journal of Membrane Biology
IS - 1-2
ER -