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Antimicrobial Agents and Chemotherapy, October 2009, p. 4231-4239, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00510-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro Antibacterial Activity of Acyl-Lysyl Oligomers against Helicobacter pylori{triangledown}

Morris O. Makobongo,1 Tchelet Kovachi,2 Hanan Gancz,1 Amram Mor,2 and D. Scott Merrell1*

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, Maryland 20814,1 Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel2

Received 17 April 2009/ Returned for modification 12 June 2009/ Accepted 14 July 2009

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, C12K-2β12, was selected for further characterization against five additional H. pylori strains (26695, J99, 7.13, SS1, and HPAG1). C12K-2β12 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 C12K-2β12. 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, C12K-2β12 showed irreversible and significant antibacterial effects and was also nonhemolytic. Our results show a significant in vitro effect of C12K-2β12 against H. pylori and suggest that OAKs may be a valuable resource for the treatment of H. pylori infection.

* Corresponding author. Mailing address: Uniformed Services University of Health Sciences F. Edward Hébert School of Medicine, Department of Microbiology and Immunology, 4301 Jones Bridge Rd., Bethesda, MD 20814. Phone: (301) 295-1584. Fax: (301) 295-3773. E-mail: dmerrell{at}usuhs.mil

{triangledown} Published ahead of print on 20 July 2009.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4231-4239, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00510-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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