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

Abstract

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.

Citric acid crosslinked natural bi-polymer-based composite hydrogels: Effect of polymer ratio and beta-cyclodextrin on hydrogel microstructure

“…for H1, H2, and H3, respectively. This result is similar to those reported that β-CD elicits poor inhibition effect on Gram-positive bacteria activity [41][42][43][44]. Thus, this antimicrobial study shows that the optimum hydrogel matrix, H0 is ideal for antimicrobial biomedical application such as wound dressing/treatment while the optimum hydrogel, H1 is suitable for microbial biotechnology application such as metabolic engineering of amino acids.…”

“…This structural characteristic makes β-CD excellent for improving loading, swelling, reinforcement and prolonging the release of materials [35,39,40]. Also, β-CD has been reported to have low or almost zero antimicrobial activity [41][42][43] especially against Gram-positive bacteria such as S. ambofaciens ATCC 23877 [43], and S. aureus [44]. To enhance fixation of hydrophobic agents as well as crosslinking, β-CD was selected to be incorporated into the hydrogel matrices.…”

Main Applications of Cyclodextrins in the Food Industry as the Compounds of Choice to Form Host–Guest Complexes

“…Some studies have used CDs to improve the production efficiency of different compounds. For instance, production efficiency of spiramycin was enhanced by CDs [ 121 ]. Modified β-CDs also increase the rate of deacetylation of spironolactone [ 122 ].…”

Interplay between Non-Coding RNA Transcription, Stringent/Relaxed Phenotype and Antibiotic Production in Streptomyces ambofaciens

“…The composition of R2 agar is reported [ 82 ]. For fermentation experiments, S. ambofaciens strains were cultivated in shake flasks at 28 °C on a rotary shaker at 200 rpm as described [ 34 , 83 ].…”

“…Spiramycin production by S. ambofaciens broth cultures was assessed by high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) as described [ 83 ]. At different time intervals, supernatants were filtered through Phenex-RC membrane (0.45 mm; Phenomenex).…”