Abstract
The bacterial cell wall represents the primary target for antimicrobial agents. Microbial destruction is accompanied by the release of potent immunostimulatory membrane constituents. Both Gram-positive and Gram-negative bacteria release a variety of lipoproteins and peptidoglycan fragments. Gram-positive bacteria additionally provide lipoteichoic acids, whereas Gram-negative bacteria also release lipopolysaccharide (LPS, endotoxin), essential component of the outer leaflet of the bacterial cell wall and one of the most potent immunostimulatory molecules known. Immune activation therefore can be considered as an adverse effect of antimicrobial destruction and killing during anti-infective treatment. In contrast to antibiotics, the use of cationic amphiphilic antimicrobial peptides allows both effective bacterial killing and inhibition of the immunostimulatory effect of the released bacterial membrane constituents. The administration of antimicrobial peptides alone or in combination with antibiotic agents thus represents a novel strategy in the antiinfective treatment with potentially important beneficial aspects. Here, data are presented which describe immunological and clinical aspects of the use of antimicrobial peptides (AMPs) as therapeutic agents to treat bacterial infection and neutralize the immunostimulatory activity of released cell wall constituents.
Keywords: Antimicrobial agents, bacterial cell wall, Gram-negative bacteria, Gram-positive bacteria, lipopolysaccharide, antimicrobial peptides, immunostimulatory membrane, toll-like receptor, EGFR, Immune activation
Current Drug Targets
Title:Bacterial Cell Wall Compounds as Promising Targets of Antimicrobial Agents II. Immunological and Clinical Aspects
Volume: 13 Issue: 9
Author(s): Tobias Schuerholz, Sabine Domming, Mathias Hornef, Aline Dupont, Ina Kowalski, Yani Kaconis, Lena Heinbockel, Jorg Andra, Patrick Garidel, Thomas Gutsmann, Sunil David, Susana Sanchez-Gomez, Guillermo Martinez de Tejada and Klaus Brandenburg
Affiliation:
Keywords: Antimicrobial agents, bacterial cell wall, Gram-negative bacteria, Gram-positive bacteria, lipopolysaccharide, antimicrobial peptides, immunostimulatory membrane, toll-like receptor, EGFR, Immune activation
Abstract: The bacterial cell wall represents the primary target for antimicrobial agents. Microbial destruction is accompanied by the release of potent immunostimulatory membrane constituents. Both Gram-positive and Gram-negative bacteria release a variety of lipoproteins and peptidoglycan fragments. Gram-positive bacteria additionally provide lipoteichoic acids, whereas Gram-negative bacteria also release lipopolysaccharide (LPS, endotoxin), essential component of the outer leaflet of the bacterial cell wall and one of the most potent immunostimulatory molecules known. Immune activation therefore can be considered as an adverse effect of antimicrobial destruction and killing during anti-infective treatment. In contrast to antibiotics, the use of cationic amphiphilic antimicrobial peptides allows both effective bacterial killing and inhibition of the immunostimulatory effect of the released bacterial membrane constituents. The administration of antimicrobial peptides alone or in combination with antibiotic agents thus represents a novel strategy in the antiinfective treatment with potentially important beneficial aspects. Here, data are presented which describe immunological and clinical aspects of the use of antimicrobial peptides (AMPs) as therapeutic agents to treat bacterial infection and neutralize the immunostimulatory activity of released cell wall constituents.
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Schuerholz Tobias, Domming Sabine, Hornef Mathias, Dupont Aline, Kowalski Ina, Kaconis Yani, Heinbockel Lena, Andra Jorg, Garidel Patrick, Gutsmann Thomas, David Sunil, Sanchez-Gomez Susana, Martinez de Tejada Guillermo and Brandenburg Klaus, Bacterial Cell Wall Compounds as Promising Targets of Antimicrobial Agents II. Immunological and Clinical Aspects, Current Drug Targets 2012; 13 (9) . https://dx.doi.org/10.2174/138945012802002438
DOI https://dx.doi.org/10.2174/138945012802002438 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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