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 th eir effects on the release and immunostimulatory activities of cell wall fr agments from gram-positive bacteria. Therefore, after Staphylococcus aureus was cultured for 4 h in the absence of antibiotics (control) and in the pr esence 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 i n 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, respe ctively), whereas protein synthesis inhibitors did not affect PG release an d 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 w hole blood was significantly higher than that of protein synthesis inhibito r or control supernatants; the amounts of these cytokines released were dir ectly proportional to the concentrations of PG and LTA in the supernatants. Enzymatic degradation of PG in the supernatants indicated that PG was main ly responsible for the observed biological reactivity.