Alternatively, loss of defense against H. pylori may be due to loss of antibacterial function of LL-37 in the milieu of the gastric mucosa. Consequently, design of antimicrobial agents that are more effective in this setting can be beneficial. Motivated by immunohistological results, the activity of LL-37 against clinical isolates of H. pylori and E. coli MG1655 under biologically relevant conditions was compared with that of the

synthetic peptide WLBU2 and the ceragenin CSA-13. This study shows that CSA-13, contrary to LL-37 and WLBU2 peptides, maintains strong bactericidal activity in the presence of mucin and after preincubation with pepsin at low pH. These conditions represent unique challenges related to H. pylori treatment, as these bacteria in the stomach are protected from the Veliparib manufacturer acidic environment by a thick mucus layer and the effectiveness of many antimicrobial drugs is greatly diminished at acidic pH [31]. Accordingly, the first effective therapy for H. pylori infection was a combination of relatively pH-insensitive antimicrobial drugs such as bismuth, tetracycline and metronidazole [33]. In addition, as the stomach periodically

empties its contents (topical therapy tends to be diluted and washed Selleck FRAX597 out) the finding that CSA-13 has bactericidal activity at much lower concentration then LL-37, after the same incubation time (3-6 hours) [11], suggests that CSA-13 may have therapeutic potential for treatment of H. pylori infection. The antibacterial activity of CSA-13, which has a smaller net charge and a unique distribution of this charge over a steroid scaffold when compared with LL-37 and WLBU2 peptides, was also found to be less inhibited by mucin isolated from gastric mucosa. Therapeutic potential based on the ability of CSA-13 to eradicate H. pylori is also supported by previously reported antibacterial activity against other bacteria strains, including clinical

isolates of Pseudomonas aeruginosa [21] and S. aureus [22]. CSA-13′s unique ability to compromise bacterial membrane integrity and the chemical nature of this low-molecular-mass Tyrosine-protein kinase BLK compound that translates to lower cost of synthesis compared to cationic antibacterial peptides suggest that CSA-13 or perhaps other ceragenins have potential for treatment of H. pylori infection, including those caused by its selleck chemical resistant strains. Conclusion Bactericidal activity of ceragenin CSA-13 is maintained after preincubation in simulated gastric juice and in the presence of mucin. This in vitro evaluation indicates a significant potential of this molecule in treatment of stomach mucosal infection.