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Short native antimicrobial peptides and engineered ultrashort lipopeptides: similarities and differences in cell specificities and modes of action

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Abstract

Due to the rapid emergence of resistant microbes to the currently available antibiotics, cationic antimicrobial peptides have attracted considerable interest as a possible new generation of anti-infective compounds. However, low cost development for therapeutic or industrial purposes requires, among other properties, that the peptides will be small and with simple structure. Therefore, considerable research has been devoted to optimizing peptide length combined with a simple design. This review focuses on the similarities and differences in the mode of action and target cell specificity of two families of small peptides: the naturally occurring temporins from the skin of amphibia and the engineered ultrashort lipopeptides. We will also discuss the finding that acylation of cationic peptides results in molecules with a more potent spectrum of activity and a higher resistance to proteolytic degradation. Conjugation of fatty acids to linear native peptide sequences is a powerful strategy to engineer novel successful anti-infective drugs.

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Abbreviations

AMP:

Antimicrobial peptide

GFP:

Green fluorescent protein

LiPs:

Lipopeptides

LPS:

Lipopolysaccharide

LPG:

Lipophosphoglycan

LTA:

Lipoteichoic acid

IM:

Inner membrane

MIC:

Minimum inhibitory concentration

OM:

Outer membrane

TNFα:

Tumor necrosis factor alpha

USLiPs:

Ultrashort lipopeptides

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Acknowledgments

This study was supported by grants from La Sapienza University of Rome and the Italian Ministero dell’Istruzione, Università e Ricerca (PRIN 2008) and partially by the German Israel Foudation to Y.S. We thank Christopher Angusch for his comments and editing the manuscript.

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  1. Istituto Pasteur-Fondazione Cenci Bolognetti, La Sapienza University of Rome, 00185, Rome, Italy

    Maria Luisa Mangoni

  2. Department of Biological Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Yechiel Shai

  3. Dipartimento di Scienze Biochimiche “A. Rossi Fanelli”, Università La Sapienza, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Maria Luisa Mangoni

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  1. Maria Luisa Mangoni
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  2. Yechiel Shai
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Correspondence to Maria Luisa Mangoni.

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Mangoni, M.L., Shai, Y. Short native antimicrobial peptides and engineered ultrashort lipopeptides: similarities and differences in cell specificities and modes of action. Cell. Mol. Life Sci. 68, 2267–2280 (2011). https://doi.org/10.1007/s00018-011-0718-2

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  • DOI: https://doi.org/10.1007/s00018-011-0718-2

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