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[Bactericidal synergy of josamycin and human polynuclear neutrophils in vitro]
1INSERM U.294, Laboratoire d'Immuno-Hématologie, CHU Xavier-Bichat, Paris.
Abstract:
Due to their high intracellular uptake, macrolides may interfere with phagocytes antibacterial system. We have studied the interaction of josamycin with bactericidal activity of human neutrophils (PMNs) or whole blood, in vitro. PMNs preincubated with josamycin (100-0.1 mg/l) display an increased phagocytic ability for K. pneumoniae, independently of the concentrations of josamycin; this effect appears to correlate with the recruitment of an additional population of phagocytizing PMNs without alteration of the mean number of PMN-associated bacteria, whatever the experimental conditions (adherent or non adherent PMNs). PMNs bactericidal function is also enhanced in the presence of josamycin in a dose-dependent manner (mean increase 60 to 370% for josamycin 0.1 to 10 mg/l). Bactericidal activity of whole human blood for P. aeruginosa (a strain resistant to the lytic effect of serum) is increased with a mean survival (CFUt min/CFU 0 min) of 24 and 71% at 60 and 120 min respectively, in the presence of josamycin 10 mg/l, and 42 and 128% in the presence of josamycin 1 mg/l, compared to the survival of the control, 68 and 166%. PMNs functions are not altered by josamycin with the exception of an enhancement of the oxidative burst induced by formylmethionyl-leucyl-phenylalanine, a synthetic compound similar to bacterial derivatives. In conclusion, we have shown a synergic interaction between phagocytes and josamycin for the killing of bacteria resistant to this antibiotic (MiC greater than 128 mg/l). This could be due either to an alteration of some PMN membrane receptors or to alterations of bacteria which render them more sensitive to natural bactericidal mechanisms and/or more able to activate these mechanisms.
Insights
Josamycin enhances the ability of human neutrophils (PMNs) to engulf and kill bacteria, even those resistant to the antibiotic. This synergistic effect boosts the body's natural defense mechanisms against infection.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Macrolides, like josamycin, are known for high intracellular uptake.
- This property may influence the host's innate immune system, specifically phagocytes.
- The interaction between macrolides and phagocyte function requires further investigation.
Purpose of the Study:
- To investigate the in vitro interaction between josamycin and the bactericidal activity of human neutrophils (PMNs) and whole blood.
- To determine if josamycin affects phagocytosis and the killing of bacteria by PMNs.
- To assess the impact of josamycin on the bactericidal activity of whole human blood against resistant bacteria.
Main Methods:
- Human neutrophils (PMNs) and whole blood were incubated with varying concentrations of josamycin.
- Phagocytic ability of PMNs for K. pneumoniae was assessed.
- Bactericidal activity against K. pneumoniae and P. aeruginosa was measured.
- Oxidative burst induced by formylmethionyl-leucyl-phenylalanine was analyzed.
Main Results:
- Josamycin significantly increased the phagocytic ability of PMNs for K. pneumoniae.
- PMN bactericidal function was enhanced in a dose-dependent manner in the presence of josamycin.
- Bactericidal activity of whole human blood against P. aeruginosa was increased by josamycin.
- Josamycin enhanced the oxidative burst in PMNs.
Conclusions:
- Josamycin exhibits a synergistic interaction with phagocytes, enhancing bacterial killing, particularly against antibiotic-resistant strains.
- This enhancement may involve alterations in PMN membrane receptors or increased bacterial susceptibility to innate immune mechanisms.
- Josamycin demonstrates potential as an adjunctive therapy to bolster host defense against bacterial infections.