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Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Bacterial Cell Wall Compounds as Promising Targets of Antimicrobial Agents II. Immunological and Clinical Aspects

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

Volume 13 , Issue 9 , 2012

Page: [1131 - 1137] Pages: 7

DOI: 10.2174/138945012802002438

Price: $65


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

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