Identification and Potency of Cyclodextrin-Lipid Inhibitors of Staphylococcus aureus α-Toxin

被引:7
作者
Weeks, Anastasia C. [1 ]
Balzli, Charles L. [1 ]
Caballero, Armando [1 ]
Tang, Aihua [1 ]
O'Callaghan, Richard [1 ]
机构
[1] Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA
关键词
alpha-toxin; Staphylococcus aureus; alpha hemolysin; Cyclodextrin; Inhibitor; Lipid; Cholesterol; Lanosterol; STREPTOCOCCUS-PNEUMONIAE KERATITIS; OCULAR INFECTIONS; BETA-CYCLODEXTRIN; CORNEAL VIRULENCE; PNEUMOLYSIN; HEMOLYSIN; IMMUNIZATION; CHOLESTEROL; CAVEOLIN-1; ROLES;
D O I
10.3109/02713683.2011.624669
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: Staphylococcus aureus, a leading cause of bacterial keratitis, secretes alpha-toxin, a cytotoxin active on the corneal epithelium. This study describes the production and testing of chemical inhibitors of alpha-toxin action. Methods: Purified alpha-toxin was titered by its ability to lyse rabbit erythrocytes in buffered saline (PBS). To prepare potential toxin inhibitors, each of 18 lipids was incorporated into a complex with methyl-beta-cyclodextrin (M beta CD) or hydroxypropyl-beta-cyclodextrin (HP beta CD). Serial dilutions of each lipid-cyclodextrin (CD-lipid) complex were mixed with alpha-toxin prior to the addition of rabbit erythrocytes. Select CD-lipid complexes were mixed with 12 hemolytic units (HU) alpha-toxin and injected into the rabbit corneal stroma so the resulting corneal erosions could be measured at 4 and 8 hours post-injection (PI). Eyes injected with toxin alone, M beta CD, or HP beta CD alone served as controls. Results: Neither form of CD alone inhibited alpha-toxin. Of the 36 complexes prepared, 6 lipid-CD complexes were found to inhibit >100 HU of alpha-toxin. Four lipid complexes able to inhibit >200 HU of alpha-toxin were tested in toxin-injected corneas; at 4 and 8 hours PI, the complexes of cholesterol or lanosterol with M beta CD and squalene or desmosterol with HP beta CD caused a significant reduction in the corneal erosion size as compared to eyes injected with alpha-toxin alone (P <= 0.05). Conclusions: Specific lipid inclusion complexes with either M beta CD or HP beta CD demonstrated a significant inhibition of alpha-toxin in both in vitro and in vivo assays. Changes in either the cyclodextrin or lipid of a complex affected the inhibitory activity.
引用
收藏
页码:87 / 93
页数:7
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