Bacteriological and ultrastructural studies on the effect of subinhibitory beta-lactam concentrations on intraphagocytic killing of Pseudomonas aeruginosa by human polymorphonuclear leukocytes.
The effect of azlocillin, ticarcillin and cefsulodin, respectively, on the susceptibility of Pseudomonas aeruginosa to the antimicrobial action of human polymorphonuclear leukocytes (PMN) was investigated under two different experimental conditions. Firstly, phagocytic capacity as well as bactericidal activity of PMN were assessed in a homologous system, i.e. the clinical isolate as well as the PMN and serum were obtained from the same patient. Secondly, ultrastructural studies were performed by electron microscopy. Preincubation of bacteria with subinhibitory beta-lactam concentrations augmented the phagocytic capacity as well as the antibacterial activity of PMN; azlocillin tended to be the most effective drug in this respect. The enhanced susceptibility to leukocyte killing is not due to an increased antibacterial action of the beta-lactams in the presence of PMN. These findings suggest that a non-immunological linkage between bacteria and PMN may exist which may be based on the interaction between bacterial- and eukaryotic surface structures, respectively. It may be assumed that the antipseudomonal beta-lactam antibiotics may cause changes in the surface structures of P. aeruginosa, thus rendering them more susceptible to phagocytosis. Preliminary data indicate that the lectins on the outer membrane of P. aeruginosa are not mannose sensitive. Electron microscopic studies revealed that azlocillin pretreatment of bacteria brought about a high undulation and a disruption of the outer membrane. These morphological changes may render bacteria more vulnerable to the antimicrobial action of PMN. It may be speculated that an interference with surface adhesins and induction of morphological changes may affect engulfment and intracellular killing of bacteria.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000648:ultrastructure; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams