Antibiotics and Polyelectrolytes Modulate Bacteriolysis and the Capacity of Bacteria to Trigger an Oxygen Burst in Neutrophils

Abstract

The invasions of tissues by pathogenic microorganisms is followed by a sequence of events which culminate in phagocytosis and the intracellular killing of the ingested agents, by “professional” phagocytes [19]. It is also expected that the rich arsenal of hydrolases present in neutrophils and macrophages, including the muralytic enzyme lysozyme is adequate to degrade the complex architecture of the bacterial cells. Surprisingly, however, most pathogenic bacteria are extremely resistant to lysozyme action [14,21] and the fate of phagocytosed bacteria in vivo is not fully known [7,8,16,23]. The sequelae of the lack of bacterial degradation by leukocytes may be the “storage” of peptidoglycan-polysaccharide or peptidoglycan-lipopolysaccharide complexes within macrophages leading to the generation of granulomas and to the initiation of prolonged immune responses. This is pivotal to the initiation of immunopathological reactions [7, 8, 16, 23]. We have recently proposed [10, 11, 12, 13, 15, 29] that the biodegradation of certain microorganisms can be mediated through the activation, by cationic agents and phospholipases, of the bacterial own autolytic wall enzymes (suicidal phenomenon) which leads to the breakdown of the rigid cell walls. On the other hand, a variety of sulfonated anionic polyelectrolytes [11–13, 15] likely to be present in inflamed issues, may inhibit the biodegradation of the walls by the autolytic enzymes.

This study was supported in part by a research grant obtained from Dr. S.M. Robbins, of Cleveland, Ohio, from a grant from the Israeli Academy of Sciences and Humanitis, and from a research grant from Deutsche Forschungsgemeinschaft