Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice

In agreement with previous studies, increased expression of hCAP-18/LL-37 was observed in gastric mucosa obtained from H. pylori infected subjects. MBC (minimum bactericidal concentration) values determined in nutrient-containing media range from 100-800 μg/ml for LL-37, 17.8-142 μg/ml for WLBU2 and 0.275-8.9 μg/ml for ceragenin CSA-13. These data indicate substantial, but widely differing antibacterial activities against clinical isolates of H. pylori. After incubation in simulated gastric juice (low pH with presence of pepsin) CSA-13, but not LL-37 or WLBU2, retained antibacterial activity. Compared to LL-37 and WLBU2 peptides, CSA-13 activity was also more resistant to inhibition by isolated host gastric mucins.These data indicate that cholic acid-based antimicrobial agents such as CSA-13 resist proteolytic degradation and inhibition by mucin and have potential for treatment of H. pylori infections, including those caused by the clarithromycin and/or metronidazole-resistant strains.Helicobacter pylori is carried by more than half of the world's adult population [1]. It can chronically colonize the human gastric mucosa, where it is found in the mucus layer and is adhered to epithelial cells [2]. Although most infected subjects remain asymptomatic, infection with H. pylori can promote severe gastritis [3] and significantly increase the risk of gastric malignancies [4,5]. In some epidemiological studies, H. pylori eradication was shown to be effective in gastric cancer prevention [6,7]. Additionally, H. pylori eradication was found to decrease the incidence and the severity of lesions with carcinogenic potential in animal models [8,9]. Natural mechanisms that protect the host from H. pylori infections depend on the function of the innate defense system in which antibacterial peptides such as cathelicidin LL-37 [10,11] and O-glycans in gastric mucin [12] play a key role.LL-37 is a proteolytically processed peptide derived from the C-terminal domain of human cathelici