Enhanced expression of ATP-binding cassette transporter A1 in non-rafts decreases the sensitivity of vascular endothelial cells to Shiga toxin.

Shiga toxin (Stx) binds to globotriaosyl ceramide (Gb3) receptors on the surface of vascular endothelial cells, which is followed by Gb3-dependent endocytosis, and initiates a cascade leading to cell damage. The Gb3 receptor is localized in lipid rafts, in which cholesterol is tightly packed primarily with sphingolipids in a liquid-ordered state. Recent studies have indicated that phosphodiesterase (PDE) type 4 inhibitors enhance the expression of ATP-binding cassette 1 (ABCA1) which promotes cholesterol efflux from non-rafts at the plasma membrane.

An interventional approach to block brain damage caused by Shiga toxin-producing Escherichia coli infection, by use of a combination of phosphodiesterase inhibitors.

We tested the combination of phosphodiesterase (PDE) 3 and PDE4 inhibitors as an interventional approach to prevent the development of brain damage after Shiga toxin (Stx)-producing Escherichia coli (STEC) infection, using mice with protein calorie malnutrition. The combination consisted of pentoxifylline and rolipram; the dose of each inhibitor was 7.5 mg/kg.

Oral therapeutic agents with highly clustered globotriose for treatment of Shiga toxigenic Escherichia coli infections.

Shiga toxin (Stx) is a major virulence factor in infection with Stx-producing Escherichia coli (STEC). We developed a series of linear polymers of acrylamide, each with a different density of trisaccharide of globotriaosylceramide (Gb3), which is a receptor for Stx, and identified Gb3 polymers with highly clustered trisaccharides as Stx adsorbents functioning in the gut. The Gb3 polymers specifically bound to both Stx1 and Stx2 with high affinity and markedly inhibited the cytotoxic activities of these toxins.

Development of a mucosal complex vaccine against oral Salmonella infection in mice.

We examined the immunogenicity of a Salmonella enterica complex vaccine (CV), consisting of flagellin and polysome purified from serotype Typhimurium LT2. CV plus cholera toxin (CT), in three oral doses given at 7-day intervals, conferred complete protection on C57BL/6 mice against lethal oral infection with a wild-type strain. It elicited mucosal IgA > IgG2a > IgG1 and systemic IgG2a > IgG1 > IgA antibodies to flagellin and polysome, and delayed footpad response (DFR) to both antigens.