EFFECT OF METAL IONS UPON THE HEAT STABILITY AND ANTIBACTERIAL ACTIVITY OF TYLOSIN-II
RESULTS OBTAINED BY THE TURBIDIMETRIC ASSAY METHOD
1965 Volume 31 Issue 5 Pages 357-364
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1965 Volume 31 Issue 5 Pages 357-364
In the previous paper1), effect of various metal ions on the heat stability and antibacterial activity of tylosin was tested by the cylinder-plate assay method with Sarcina lutea and a modified streptomycin assay agar of pH 8.5. However, results obtained revealed that changes in the drug activity by treatment with metal ions in acidic condition at elevated temperature could not be evaluated correctly due to the defect of assay technique.
In the present work, tylosin activity was measured by the turbidimetric assay method with Staphylococcus aureus H and the double strength Difco nutrient broth of pH 7.0, and the activity was expressed in a 50% inhibition dose (ID50) according to TREFFERS2).
Results obtained may be summarized as follows:
1. Tylosin and its degradation product desmycosin exhibited higher antimicrobial activity in alkaline than in neutral or acid side. At pH 8.0, desmycosin showed three times as muchh activity as that of tylosin, while at pH 6.0, tylosin was two times more active than desmycosin (Table 1).
2. No appreciable decrease in the activity of both antibiotics was observed by heating them at 100°C for 1 hour in SÖRENSEN phosphate buffer solution of pH 6.0, 7.0 and 8.0, whereas below pH 4.5, tylosin was easily converted into desmycosin (Table 3).
3. At pH 7.0 and 8.0, the presence of metal ions in the test solution of either phosphate buffer or Difco nutrient broth, did not affect the antibacterial activity of tylosin on heating at 100°C for 1 hour, on the other hand, a marked dercease in the activity was observed in the aqueous test solution containing Al+++, Fe+++ or Sn++, each at 300 ppm level, and similar tendency was noted with Al+++ and Fe+++ in the phosphate buffer as in the nutrient broth of pH 6.0 (Table 2).
4. Fe+++ compounds of different anionic forms gave the same rate of inactivation to tylosin, which might be suggesting that the effect is mainly due to the cation, ferric ion itself (Table 6).
The addition of Na-hexameta phosphate to tylosin solution which had been decreased in the activity with Fe+++ resulted in failure to recover the lowered activity (Table 5).
