Bacterial cell wall compounds as promising targets of antimicrobial agents II. Immunological and clinical aspects.
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.
Universitätsklinikum Aachen, Dept. of Intensive Care and Intermediate Care,Pauwelsstr. 30, D-52074 Aachen, Germany.
Tobias
T
Schuerholz
Sabine
S
Dömming
Mathias
M
Hornef
Aline
A
Dupont
Ina
I
Kowalski
Yani
Y
Kaconis
Lena
L
Heinbockel
Jörg
J
Andrä
Patrick
P
Garidel
Thomas
T
Gutsmann
Sunil
S
David
Susana
S
Sánchez-Gómez
Guillermo
G
Martinez de Tejada
Klaus
K
Brandenburg
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans
D000276:Adjuvants, Immunologic; D000890:Anti-Infective Agents