| Abstract
| - The antibiotics known as aminoglycosides are commonly used totreat severe infections causedby Gram-negative bacteria. Unfortunately, they often lead to acuterenal failure after their accumulationin the lysosomes of renal cells, where an inhibition of thephospholipid catabolism is observed. Thelipopeptidic antibiotic daptomycin has been shown to reduce thenephrotoxicity of aminoglycosides, butthe exact mechanism of this protection is still unknown. In thepresent study, Fourier transform infraredspectroscopy (FTIR) has been used to monitor the hydrolysis ofphosphatidylcholine by phospholipaseA2 (PLA2) from Najamocambiquemocambique venom in the presence ofvarious aminoglycosides and/or daptomycin. Gentamicin and amikacin inhibited the reaction inits early stage. Kanamycin A,tobramycin, and especially kanamycin B enhanced the initialenzyme activity by reducing the lag time.After the initiation period, the reaction proceeded at a muchslower rate in the presence of gentamicin.On the other hand, daptomycin led to dramatic alterations of thehydrolysis profile: the initial latencyperiod was eliminated, and the maximal extent of hydrolysis wasreduced. When both daptomycin andany of the aminoglycosides were present, the latency period alsodisappeared, and the phospholipaseactivity was higher than with the lipopeptide alone. The mostdrastic change occurred with gentamicin,which was the most inhibitory aminoglycoside when used alone but workedsynergistically with daptomycinto yield the most dramatic activation of PLA2.
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