ENHANCED KILLING OF PENICILLIN-TREATED GRAM-POSITIVE COCCI BY HUMAN-GRANULOCYTES - ROLE OF BACTERIAL AUTOLYSINS, CATALASE, AND GRANULOCYTE OXIDATIVE PATHWAYS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 58  (2) , 133-143
Abstract
Staphylococci pretreated with subminimal inhibitory concentrations (subMIC) of cell-wall active antibiotics exhibited increased susceptibility to killing by human polymorphonuclear leukocytes (PMN), even when phagosome information was impaired by the mold metabolite, cytochalasin B. To investigate the role of specific bacterial factors in the process, organisms lacking catalase (streptococci) or cell-wall autolytic enzymes were studied and compared to findings with Staphylococcus aureus 502A. Neutrophil factors were studied using inhibitors, O2 radical scavengers, myeloperoxidase (MPO)-deficient PMN, or PMN from a patient with chronic granulomatous disease (CGD). Documentation of the enhanced susceptibility of the streptococcal strains to killing by PMN following subMIC penicillin pretreatment required the use of cytochalasin B. Enhancement of killing occurred independent of the presence or absence of bacterial autolysis or catalase. SubMIC penicillin pretreatment of S. pneumoniae R36A specifically promoted the susceptibility of these organisms to killing by myeloperoxidase (MPO)-mediated mechanisms (enhancement lost using MPO-deficient or azide-treated cells). Factors other than MPO or toxic O2 products generated by the PMN respiratory burst are responsible for enhanced killing of penicillin-pretreated S. aureus 502A (enhancement preserved using MPO-deficient, azide-treated or chronic granulomatous disease patient cells). Methods to study the interaction of antimicrobial agents and PMN in the killing of microorganisms were defined. Penicillin treatment can change the susceptibility of gram-positive cocci to the action of specific PMN microbicidal mechanisms. The mechanism of the enhancement appears to be bacterial strain-dependent and not predictable by bacterial autolysin or catalase activity.