Antibacterial action of bile acids against Helicobacter pylori and changes in its ultrastructural morphology: effect of unconjugated dihydroxy bile acid

Abstract

Although it has been shown that bile acids possess antibacterial activity against Helicobacter pylori, few reports on their activity have been published. We determined the minimum inhibitory concentration at 72 h of various unconjugated and conjugated bile acids against laboratory standard strains and clinical isolates of H. pylori, and studied morphologic changes of H. pylori under the scanning electron microscope during treatment with deoxycholic acid and ursodeoxycholic acid at the minimum inhibitory concentrations for 24 h. We found that only the unconjugated form of dihydroxy bile acid has antibacterial activity. The minimum inhibitory concentration of deoxycholic acid is 200-400 microg/ml, that of chenodeoxycholic acid is similar to that of deoxycholic acid, and that of ursodeoxycholic acid is 400-800 microg/ml. The morphology of H. pylori changed from its primary rodlike shape to a spherical shape with blebs on the cell surface, and was further degraded to an irregularly condensed mass, following an increase in bile acid. This morphologic change in H. pylori was different from the change to a spherical shape caused by amoxicillin. On the basis of these results, it seems that unconjugated dihydroxy bile acid might be a candidate drug for eradication of H. pylori, but further investigations of the clinical usefulness of bile acid for this purpose should be done.

TheHelicobacter pylori flaA1andwbpBGenes Control Lipopolysaccharide and Flagellum Synthesis and Function

“…Disruption of flaA1 or wbpB affects the barrier properties of the outer membrane. Defects in LPS synthesis often correlate with higher sensitivity of bacteria to killing by serum, detergents (SDS or bile salts) (29), or hydrophobic antibiotics (novobiocin) (67) and with decreased virulence properties in animal models (56,70). Hence, the sensitivity of the flaA1 and wbpB mutants to each of these compounds was investigated.…”

“…Harvested bacteria were diluted to an optical density at 600 nm (OD 600 ) of 1 in BHI-YE. A 30-l volume of cell suspension was added to 175 l of BHI-YE supplemented with the appropriate antibiotics and/or detergents, with concentrations up to 15 g/ml for novobiocin, 0.02% for SDS, and 0.18 mg/ml for bile salts (50% sodium cholate, 50% sodium deoxycholate (Sigma) (29). The assays were performed three times with independent cultures in 96-well plates incubated for 4 to 5 days with agitation at 37°C under microaerophilic conditions.…”

Detection of Helicobacter pylori in faeces by culture, PCR and enzyme immunoassay

“…The mechanism by which viable H. pylori can be excreted in the faeces is not properly understood. H. pylori colonises areas of the stomach which are not in contact with bile [16] and the bacterium is known to be sensitive to bile. As bile is present in the duodenum and the colon [17], the organism may not survive transit through the alimentary tract in association with the faeces.…”

Role of the HefC Efflux Pump inHelicobacter pyloriCholesterol-Dependent Resistance to Ceragenins and Bile Salts

“…Bile salt concentrations of ϳ2 mM (ϳ1,000 g/ml) are typically found in human bile (34). A few studies have investigated the bactericidal effects of bile salts on H. pylori using rich medium containing serum or blood (which contains cholesterol) (14,15,22,33), but no study has yet investigated the effects in a chemically defined, cholesterolfree medium, nor has there been a comprehensive comparison among the many bile salt derivatives found in vivo.…”