Related Experiment Videos
[Synergism of josamycin and oxidation against Staphylococcus aureus]
1INSERM, U. 294, CHU Xavier Bichat, Paris.
Abstract:
We have previously reported that josamycin (JM) displayed a bactericidal synergy with human neutrophils (PMN) in vitro without altering significantly various cell functions (Labro et al., Path. Biol., 1989, 37, 329-334). Since JM may concentrate into phagocytes, and partly at least into lysosomes, it was of interest to analyze if the presence of this molecule could enhance the bactericidal activity of some acellular systems mimicking those acting inside the phagolysosome, using Staphylococcus aureus as the bacterial target. Erythromycin (EM) was assessed comparatively. While none of the macrolides increased the lethal effect of a crude PMN extract (02-independent system), an enhancement of the bacterial killing by an oxidant stress was observed in the presence of the 2 molecules. However, the effect of JM was strongest that the one induced by EM: S. aureus survival after exposure to xanthine + xanthine oxidase was 38 +/- 17.2% and it was reduced to 11 +/- 5.0 and 23 +/- 15.6 with JM (30 and 3 mg/l) and 22 +/- 13.1 and 23 +/- 9.7 with EM (30 and 3 mg/l). On the other hand, S. aureus survival after exposure to H2 O2 was reduced only by JM (16 +/- 9.4 and 32 +/- 6.9% versus 43 +/- 11.2% for controls). Pretreatment of S. aureus for 60 min by JM or EM did not alter the sensitivity of the bacteria either to PMN or to acellular systems. These data suggest that JM (and at a lesser degree EM) could be transformed by reactive oxygen species generated inside the phagolysosome to become more toxic for the bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Josamycin (JM) and erythromycin (EM) enhance bacterial killing by reactive oxygen species, mimicking phagolysosome conditions. JM showed a stronger effect, suggesting macrolides can be activated by oxidants to increase toxicity against Staphylococcus aureus.
Area of Science:
- Microbiology
- Biochemistry
- Immunology
Context:
- Josamycin (JM) previously showed synergistic bactericidal activity with human neutrophils (PMN).
- JM and erythromycin (EM) may concentrate in phagocytes and lysosomes.
- Investigating acellular systems mimicking phagolysosomal conditions to understand macrolide activity.
Purpose:
- To evaluate if josamycin (JM) and erythromycin (EM) can enhance the bactericidal activity of acellular systems mimicking phagolysosomes.
- To determine the comparative efficacy of JM and EM in an oxidant stress environment against Staphylococcus aureus.
- To assess if macrolide pretreatment affects bacterial sensitivity to neutrophils or acellular killing systems.
Summary:
- Neither JM nor EM enhanced killing in a crude PMN extract (O2-independent system).
- Both macrolides enhanced bacterial killing under oxidant stress (xanthine + xanthine oxidase), with JM showing a stronger effect.
- JM, but not EM, reduced Staphylococcus aureus survival when exposed to H2O2, suggesting JM is more potent in oxidant-dependent killing.
Impact:
- Data suggest JM and EM can be transformed by reactive oxygen species (ROS) within the phagolysosome.
- This transformation potentially increases the macrolides' toxicity towards bacteria like Staphylococcus aureus.
- The findings offer insights into novel mechanisms of antibiotic action and synergy in the presence of host immune defenses.