Antibiotic-induced release of lipoteichoic acid and peptidoglycan from Staphylococcus aureus: quantitative measurements and biological reactivities.
Antibiotics with different mechanisms of action may vary with respect to their effects on the release and immunostimulatory activities of cell wall fragments from gram-positive bacteria. Therefore, after Staphylococcus aureus was cultured for 4 h in the absence of antibiotics (control) and in the presence of beta-lactam antibiotics (imipenem, flucloxacillin, or cefamandole) and protein synthesis-inhibiting antibiotics (erythromycin, clindamycin, or gentamicin), the lipoteichoic acid (LTA) and peptidoglycan (PG) levels in the bacterial supernatants were measured. beta-Lactam antibiotics greatly enhanced the release of LTA and PG (4- to 9-fold and 60- to 85-fold, respectively), whereas protein synthesis inhibitors did not affect PG release and even inhibited the release of LTA compared to the amount of LTA released in control cultures. The capacity of beta-lactam supernatants to stimulate the production of tumor necrosis factor alpha and interleukin-10 in human whole blood was significantly higher than that of protein synthesis inhibitor or control supernatants; the amounts of these cytokines released were directly proportional to the concentrations of PG and LTA in the supernatants. Enzymatic degradation of PG in the supernatants indicated that PG was mainly responsible for the observed biological reactivity.
van Langevelde
P
P
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. J.van_Dissel@Thuisnet.LeidenUniv.NL
van Dissel
J T
JT
Ravensbergen
E
E
Appelmelk
B J
BJ
Schrijver
I A
IA
Groeneveld
P H
PH
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000097:blood; D007769:Lactams; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000276:immunology / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013682:Teichoic Acids / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D007769:Lactams; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011500:Protein Synthesis Inhibitors; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C009900:lipoteichoic acid