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

Leszczyńska K, Namiot A, Fein DE, Wen Q, Namiot Z, Savage PB, Diamond S, Janmey PA, Bucki R - BMC Microbiol. (2009)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Diagnostic Microbiology, Medical University of Bialystok, 15-230 Bialystok, Poland. katles@onet.eu

ABSTRACT

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.

Conclusion: 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.

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Presence of hCAP-18/LL-37 peptide in mucosal biopsies from the human stomach detected using immunohistochemical analysis with monoclonal antibodies to human CAP-18/LL-37. Samples A/B and C/D represent the specimens obtained from non-infected and H. pylori infected subjects respectively. Data shown are representative of five experiments.
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Figure 1: Presence of hCAP-18/LL-37 peptide in mucosal biopsies from the human stomach detected using immunohistochemical analysis with monoclonal antibodies to human CAP-18/LL-37. Samples A/B and C/D represent the specimens obtained from non-infected and H. pylori infected subjects respectively. Data shown are representative of five experiments.

Mentions: Microscopic images of mucosal biopsies after immunohistochemical evaluation with anti-hCAP-18/LL-37 antibody are shown in Figure 1. The DAB-positive staining indicates the presence of the LL-37 peptide and/or its parent protein hCAP-18. High intensity DAB staining (indicated by brown color) at the mucus-producing epithelial cells and fundic glands indicates high accumulation of hCAP-18/LL-37 peptide most likely driven by LL-37 specific interaction with mucin, which was reported in previous studies [23,24]. The distribution of hCAP-18/LL-37 in the more differentiated epithelial cell population of the gastric mucosa differs from that found for human β-defensin 2 [10] or lysozyme [25] but is similar to that observed in the colon [26]. Gastric mucosal biopsies from patients infected with H. pylori show higher intensity of DAB staining compared to those obtained from non-infected subjects. According to previous reports, this result indicates a host defense response to H. pylori [11], which is partly based on increased expression of hCAP-18/LL-37 by gastric epithelial cells.


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

Leszczyńska K, Namiot A, Fein DE, Wen Q, Namiot Z, Savage PB, Diamond S, Janmey PA, Bucki R - BMC Microbiol. (2009)

Presence of hCAP-18/LL-37 peptide in mucosal biopsies from the human stomach detected using immunohistochemical analysis with monoclonal antibodies to human CAP-18/LL-37. Samples A/B and C/D represent the specimens obtained from non-infected and H. pylori infected subjects respectively. Data shown are representative of five experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2748089&req=5

Figure 1: Presence of hCAP-18/LL-37 peptide in mucosal biopsies from the human stomach detected using immunohistochemical analysis with monoclonal antibodies to human CAP-18/LL-37. Samples A/B and C/D represent the specimens obtained from non-infected and H. pylori infected subjects respectively. Data shown are representative of five experiments.
Mentions: Microscopic images of mucosal biopsies after immunohistochemical evaluation with anti-hCAP-18/LL-37 antibody are shown in Figure 1. The DAB-positive staining indicates the presence of the LL-37 peptide and/or its parent protein hCAP-18. High intensity DAB staining (indicated by brown color) at the mucus-producing epithelial cells and fundic glands indicates high accumulation of hCAP-18/LL-37 peptide most likely driven by LL-37 specific interaction with mucin, which was reported in previous studies [23,24]. The distribution of hCAP-18/LL-37 in the more differentiated epithelial cell population of the gastric mucosa differs from that found for human β-defensin 2 [10] or lysozyme [25] but is similar to that observed in the colon [26]. Gastric mucosal biopsies from patients infected with H. pylori show higher intensity of DAB staining compared to those obtained from non-infected subjects. According to previous reports, this result indicates a host defense response to H. pylori [11], which is partly based on increased expression of hCAP-18/LL-37 by gastric epithelial cells.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Diagnostic Microbiology, Medical University of Bialystok, 15-230 Bialystok, Poland. katles@onet.eu

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus