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


RESULTS
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.


CONCLUSIONS
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.
Leszczyńska
Katarzyna
K
Department of Diagnostic Microbiology, Medical University of Bialystok, 15-230 Bialystok, Poland. katles@onet.eu
Namiot
Andrzej
A
Fein
David E
DE
Wen
Qi
Q
Namiot
Zbigniew
Z
Savage
Paul B
PB
Diamond
Scott
S
Janmey
Paul A
PA
Bucki
Robert
R
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005750:Gastric Juice / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013256:Steroids / Q000378:metabolism / Q000494:pharmacology*; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D013256:Steroids; C520840:WLBU2 peptide; C521528:ceragenin CSA-13; D054804:Cathelicidins