Interactions between antibiotics and XXXX neutrophils in the killing of staphylococci.

@entity1 @entity801 @entity2176 @entity114 @entity794 @entity5132 @entity2389 @entity3397
Normal and antibiotic-pretreated staphylococci were incubated with @entity1 neutrophils to determine the interactions between cells and antimicrobials in the killing of the organisms. @entity794 502A pretreated during log-phase growth with subinhibitory ((1/4) minimum inhibiting concentration) (MIC) concentrations of @entity3397 were more susceptible to killing by normal neutrophils than untreated bacteria (intracellular survival 0.17+/-0.04 vs. 1.5+/-0.38%, mean+/-SEM, respectively, at 35 min in 14 experiments; P < 0.01 by t test). Furthermore, this enhanced susceptibility to killing was observed even when phagosome formation was inhibited by @entity2389 (65.6+/-4.6% pencillintreated vs. 30.5+/-4.5% untreated killed at 30 min in 14 experiments, P < 0.001). Pretreatment of @entity794 with @entity2176 similarly enhanced susceptibility to killing by @entity2389 -treated polymorphonuclear leukocytes (PMN), whereas pretreatment with @entity801 did not. The enchancement of killing by pretreatment with cell wall-active antibiotics was present in a dose-response fashion to 1/16th the MIC. It required specific antimicrobial activity; i.e., @entity114 activity was inhibited by penicillinase or by incubation with bacteria at 4 degrees C. It also required active cellular metabolism and intact neutrophils. For antibiotic-pretreated bacteria to be killed by normal and @entity2389 -treated cells, phagocytosis or binding to the cells was essential via a serum opsonindependent mechanism. In experiments with the @entity2389 -treated cells, all bound @entity114 -treated bacteria were killed vs. only a fraction (70%) of the bound untreated bacteria. @entity114 in 10 times the MIC had no direct effects on PMN phagocytic, metabolic, or microbicidal functions against a nonsusceptible organism, @entity5132 . The results indicate a cooperative effect between cell wall-active antibiotics at low concentrations and @entity1 PMN in the killing of staphylococci. The model establishes conditions for the study of the mechanisms involved in the cooperation of these bactericidal systems.
