Journal Article

<i>In vitro</i> activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates

U. Pag, M. Oedenkoven, N. Papo, Z. Oren, Y. Shai and H.-G. Sahl

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 2, pages 230-239
Published in print February 2004 | ISSN: 0305-7453
Published online February 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh083
In vitro activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates

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Objectives: Increasing resistance of pathogenic bacteria to antibiotics is a severe problem in health care and has intensified the search for novel drugs. Cationic antibacterial peptides are the most abundant antibiotics in nature and have been frequently proposed as new anti-infective agents. Here, a group of diastereomeric (containing d- and l-amino acids) peptides is studied regarding their potency against multiply resistant clinical isolates and their modes of action against Gram-positive cocci.

Methods: MIC determinations and chequerboard titrations followed established procedures. Mode of action studies included killing kinetics and a series of experiments designed to characterize the impact of the diastereomeric peptides on bacterial membranes.

Results: The tested diastereomers displayed high antimicrobial and broad spectrum activity with amphipathic-2D being the most active peptide. Synergic activities were observed with individual strains. Mode of action studies clearly demonstrated that the cytoplasmic membrane is a primary target for the peptides and that membrane disruption constitutes a significant bactericidal activity for the major fraction of a bacterial population. However, depending on the indicator strain, the results also suggest that additional molecular events contribute to the overall activity.

Keywords: Keywords: synergic activities, membrane permeabilization, intracellular targets

Journal Article.  6244 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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