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

• Published in: BMC microbiology Vol. 9; no. 1; p. 187
• Main Authors: Leszczyńska, Katarzyna, Namiot, Andrzej, Fein, David E, Wen, Qi, Namiot, Zbigniew, Savage, Paul B, Diamond, Scott, Janmey, Paul A, Bucki, Robert
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.09.2009; BioMed Central; BMC
• Subjects: Adenocarcinoma; Anatomy & physiology; Anti-Bacterial Agents - pharmacology; Anti-infective agents; Antibacterial activity; Antibacterial agents; Antimicrobial agents; Antimicrobial Cationic Peptides - metabolism; Antimicrobial Cationic Peptides - pharmacology; Bacteria; Bactericidal activity; Blood; cathelicidins; Cell Line, Tumor; Clarithromycin; Clinical isolates; Data processing; Drug resistance; Drug resistance in microorganisms; Drug therapy; Gastric juice; Gastric Juice - microbiology; Gastric mucosa; Gastric Mucosa - metabolism; Genetic aspects; Health aspects; Helicobacter infections; Helicobacter Infections - metabolism; Helicobacter pylori; Helicobacter pylori - drug effects; Humans; Infection; Microbial Sensitivity Tests; mucin; Mucins; Nutrient concentrations; Pepsin A; Peptides; pH effects; Proteolysis; Research article; Risk factors; Staphylococcus infections; Steroid hormones; Steroids - metabolism; Steroids - pharmacology; Stomach; Studies; Poland; United States
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/1471-2180-9-187

The worldwide appearance of drug-resistant strains of H. pylori motivates a search for new agents with therapeutic potential against this family of bacteria that colonizes the stomach, and is associated with adenocarcinoma development. This study was designed to assess in vitro the anti-H. pylori potential of cathelicidin LL-37 peptide, which is naturally present in gastric juice, its optimized synthetic analog WLBU2, and the non-peptide antibacterial agent ceragenin CSA-13. 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 microg/ml for LL-37, 17.8-142 microg/ml for WLBU2 and 0.275-8.9 microg/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.