In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 53, No. 10 ( 2009-10), p. 4231-4239
Abstract:
The gastric pathogen Helicobacter pylori has developed resistance to virtually all current antibiotics; thus, there is a pressing need to develop new anti- H. pylori therapies. The goal of this work was to evaluate the antibacterial effect of oligo-acyl-lysyl (OAK) antimicrobial peptidomimetics to determine if they might represent alternatives to conventional antibiotic treatment of H. pylori infection. A total of five OAK sequences were screened for growth-inhibitory and/or bactericidal effects against H. pylori strain G27; four of these sequences had growth-inhibitory and bactericidal effects. The peptide with the highest efficacy against strain G27, C 12 K-2β 12 , was selected for further characterization against five additional H. pylori strains (26695, J99, 7.13, SS1, and HPAG1). C 12 K-2β 12 displayed MIC and minimum bactericidal concentration (MBC) ranges of 6.5 to 26 μM and 14.5 to 90 μM, respectively, across the six strains after 24 h of exposure. G27 was the most sensitive H. pylori strain (MIC = 6.5 to 7 μM; MBC = 15 to 20 μM), whereas 26695 was the least susceptible strain (MIC = 25 to 26 μM; MBC = 70 to 90 μM). H. pylori was completely killed after 6 to 8 h of incubation in liquid cultures containing two times the MBC of C 12 K-2β 12 . The OAK demonstrated strong in vitro stability, since efficacy was maintained after incubation at extreme temperatures (4°C, 37°C, 42°C, 50°C, 55°C, 60°C, and 95°C) and at low pH, although reduced killing kinetics were observed at pH 4.5. Additionally, upon transient exposure to the bacteria, C 12 K-2β 12 showed irreversible and significant antibacterial effects and was also nonhemolytic. Our results show a significant in vitro effect of C 12 K-2β 12 against H. pylori and suggest that OAKs may be a valuable resource for the treatment of H. pylori infection.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.00510-09
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2009
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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