Influence of LY146032 on human polymorphonuclear leucocytes in vitro
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P Van der Auwera1, G Petrikkos, T Matsumoto
1Service de Médecine et Laboratoire d'Investigation Clinique H. J. Tagnon, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Belgium.
Abstract:
LY 146032 is a new acidic lipopeptide antibiotic with high in-vitro activity against Gram-positive bacteria. We have studied the influence of LY 146032 on the functions of polymorphonuclear leucocytes with two strains of Staphylococcus aureus, one susceptible to oxacillin and one resistant. LY 146032 (10 mg/l) was found to have no influence on superoxide generation stimulated by phorbol myristate acetate, nor on phagocytosis of opsonized Staph. aureus, furthermore there was no effect on chemotaxis in agar stimulated by opsonized zymosan. LY 146032 (MIC and MIC/4) did not modify the intracellular killing of the two strains when they were preincubated, or when the antibiotic was added either at the time or after the completion of phagocytosis both in aerobic and in strict anaerobic conditions. However, in aerobic conditions, LY 146032 was able to prevent the overgrowth of phagocytosed Staph. aureus after 24 h of incubation. The intracellular concentration of LY 146032, measured by microbiological assay, was 60% of the extracellular concentration.
Insights
The novel antibiotic LY 146032 shows high in-vitro activity against Gram-positive bacteria. While not affecting key polymorphonuclear leucocyte functions, it prevents Staphylococcus aureus overgrowth within host cells under aerobic conditions.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- LY 146032 is a novel acidic lipopeptide antibiotic.
- It exhibits potent in-vitro activity against Gram-positive bacteria.
Purpose of the Study:
- To investigate the effects of LY 146032 on polymorphonuclear leucocyte (PMN) functions.
- To assess LY 146032's impact on Staphylococcus aureus interactions with PMNs.
Main Methods:
- Assessed superoxide generation, phagocytosis, and chemotaxis of PMNs.
- Evaluated intracellular killing of Staphylococcus aureus by PMNs.
- Measured intracellular antibiotic concentration via microbiological assay.
Main Results:
- LY 146032 did not influence PMN superoxide generation, phagocytosis, or chemotaxis.
- The antibiotic did not affect intracellular killing of Staphylococcus aureus under aerobic or anaerobic conditions.
- LY 146032 prevented Staphylococcus aureus overgrowth within phagocytosed cells after 24 hours in aerobic conditions.
- Intracellular LY 146032 concentration reached 60% of extracellular levels.
Conclusions:
- LY 146032 does not impair key PMN functions essential for bacterial clearance.
- The antibiotic demonstrates a novel mechanism by preventing intracellular bacterial overgrowth.
- LY 146032 shows potential as an adjunct therapy for Gram-positive bacterial infections.