title: [Synergism of josamycin and oxidation against Staphylococcus aureus].
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)
authors.affiliation: INSERM, U. 294, CHU Xavier Bichat, Paris.
authors.forename: M T
authors.initials: MT
authors.lastname: Labro
authors.forename: J
authors.initials: J
authors.lastname: el Benna
mesh_terms: D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004917:Erythromycin / Q000494:pharmacology; D066298:In Vitro Techniques; D015570:Josamycin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009504:Neutrophils; D010545:Peroxides / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013481:Superoxides / Q000494:pharmacology*
chemical_list: D010545:Peroxides; D013481:Superoxides; D004917:Erythromycin; D015570:Josamycin
vernacular_title: Synergie entre la josamycine et un stress oxydant pour la bactéricidie de Staphylococcus aureus.