Neutrophil-anti-microbial interaction in the established infection: effect on Staphylococcus aureus.
OBJECTIVE
To determine if differences in drug-related Staphylococcus aureus killing, associated in vivo with neutropenia, is neutrophil-related in vitro, and the mechanisms of this interaction.


METHODS
To evaluate the influence of living neutrophils on drug-S. aureus interactions, cell wall enzymes, the PBPs, were isolated and their binding to five (beta lactam and other) antibiotics was evaluated following incubation (or not) with neutrophils. S. aureus killing by the test drugs was assayed in growth media of sterile filtered abscess fluid, either neutropenic infected or normal infected. At MBCs for the test isolate, each drug or saline control was incubated with S. aureus 10(6)and dilution-plated.


RESULTS
Neutrophil incubation with S. aureus eliminated the S. aureus PBP-2 band in all Western blots irrespective of the drug used to tag the PBPs. Time-kill of S. aureus grown in neutropenic or normal abscess fluid showed greater kill by all drugs in neutropenic abscess fluid (p=0.029 6h incubation). Killing difference between the media correlates with drug PBP-2 activity.


CONCLUSIONS
Drug activity against S. aureus in vitro is changed by neutrophil incubation. The neutrophil-induced loss of S. aureus PBP-2 drug binding suggests novel host-bacterial interaction that may impinge on drug treatment of S. aureus infections.
Koomer
Ajoy
A
University of Missouri-Kansas City School of Medicine, 2411 Holmes St, Kansas City, MO 64108, USA.
Quinn
Tim
T
Bamberger
David
D
Herndon
Betty L
BL
D000038:Abscess / Q000188:drug therapy / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000502:physiology*; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*
D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins