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Sera from patients with endocarditis and bacteremia due to Staphylococcus aureus were compared for peptidoglycan-binding capacity with those from normal blood donors. Those patients treated with beta-lactam antibiotics had higher antigen-binding levels than normal donors and patients treated exclusively with vancomycin (P less than 0.01). The factor responsible for this activity was purified by affinity chromatography from a normal donor and shown to be an immunoglobulin. Specificity studies indicated that the immunodominant determinant was a peptide sequence found in peptidoglycan precursors. Since soluble peptidoglycan molecules having the precursor peptide sequence are known to be secreted by some gram-positive bacteria like Micrococcus luteus when grown in the presence of beta-lactam antibiotics, these soluble molecules may constitute the "natural" immunogen. Such a hypothesis is consistent with the study of the peptidoglycan-binding capacities in the sera of these patients during the course of treatment. For most of the responding patients studied (four of four with bacteremia and seven of nine with endocarditis), a significant increase in peptidoglycan-binding capacity was observed in sera taken 1 to 5 weeks after the initiation of beta-lactam antibiotic therapy (compared with the initial serum studied). No such increase in the peptidoglycan-binding capacity over a similar time span was noted in the sera of people not receiving beta-lactam antibiotics (none of seven).

infection and immunity

Antibody levels to bacterial peptidoglycan in human sera during the time course of endocarditis and bacteremic infections caused by Staphylococcus aureus