Stimulatory Effects of Methyl-β-cyclodextrin on Spiramycin Production and Physical–Chemical Characterization of Nonhost@Guest Complexes

Spiramycin is a macrolide
antibiotic and antiparasitic that is
used to treat toxoplasmosis and various other infections of soft tissues.
In the current study, we evaluated the effects of α-cyclodextrin,
β-cyclodextrin, or methyl-β-cyclodextrin supplementation
to a synthetic culture medium on biomass and spiramycin production
by Streptomyces ambofaciens ATCC 23877.
We found a high stimulatory effect on spiramycin production when the
culture medium was supplemented with 0.5% (w/v) methyl-β-cyclodextrin,
whereas α-cyclodextrin or β-cyclodextrin weakly enhanced
antibiotic yields. As the stimulation of antibiotic production could
be because of spiramycin complexation with cyclodextrins with effects
on antibiotic stability and/or efflux, we analyzed the possible formation
of complexes by physical–chemical methods. The results of Job
plot experiment highlighted the formation of a nonhost@guest complex
methyl-β-cyclodextrin@spiramycin I in the stoichiometric ratio
of 3:1 while they excluded the formation of complex between spiramycin
I and α- or β-cyclodextrin. Fourier-transform infrared
spectroscopy measurements were then carried out to characterize the
methyl-β-cyclodextrin@spiramycin I complex and individuate the
chemical groups involved in the binding mechanism. These findings
may help to improve the spiramycin fermentation process, providing
at the same time a new device for better delivery of the antibiotic
at the site of infection by methyl-β-cyclodextrin complexation,
as it has been well-documented for other bioactive molecules.