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Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction.

Publication ,  Journal Article
Barry, DP; Asim, M; Leiman, DA; de Sablet, T; Singh, K; Casero, RA; Chaturvedi, R; Wilson, KT
Published in: PLoS One
February 28, 2011

Helicobacter pylori infects half the world's population, and carriage is lifelong without antibiotic therapy. Current regimens prescribed to prevent infection-associated diseases such as gastroduodenal ulcers and gastric cancer can be thwarted by antibiotic resistance. We reported that administration of 1% D,L-α-difluoromethylornithine (DFMO) to mice infected with H. pylori reduces gastritis and colonization, which we attributed to enhanced host immune response due to inhibition of macrophage ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Although no ODC has been identified in any H. pylori genome, we sought to determine if DFMO has direct effects on the bacterium. We found that DFMO significantly reduced the growth rate of H. pylori in a polyamine-independent manner. Two other gram-negative pathogens possessing ODC, Escherichia coli and Citrobacter rodentium, were resistant to the DFMO effect. The effect of DFMO on H. pylori required continuous exposure to the drug and was reversible when removed, with recovery of growth rate in vitro and the ability to colonize mice. H. pylori exposed to DFMO were significantly shorter in length than those untreated and they contained greater internal levels of ATP, suggesting severe effects on bacterial metabolism. DFMO inhibited expression of the H. pylori virulence factor cytotoxin associated gene A, and its translocation and phosphorylation in gastric epithelial cells, which was associated with a reduction in interleukin-8 expression. These findings suggest that DFMO has effects on H. pylori that may contribute to its effectiveness in reducing gastritis and colonization and may be a useful addition to anti-H. pylori therapies.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

February 28, 2011

Volume

6

Issue

2

Start / End Page

e17510

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Protein Transport
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Interleukin-8
  • Humans
  • Helicobacter pylori
  • Helicobacter Infections
  • General Science & Technology
 

Citation

APA
Chicago
ICMJE
MLA
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Barry, D. P., Asim, M., Leiman, D. A., de Sablet, T., Singh, K., Casero, R. A., … Wilson, K. T. (2011). Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction. PLoS One, 6(2), e17510. https://doi.org/10.1371/journal.pone.0017510
Barry, Daniel P., Mohammad Asim, David A. Leiman, Thibaut de Sablet, Kshipra Singh, Robert A. Casero, Rupesh Chaturvedi, and Keith T. Wilson. “Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction.PLoS One 6, no. 2 (February 28, 2011): e17510. https://doi.org/10.1371/journal.pone.0017510.
Barry DP, Asim M, Leiman DA, de Sablet T, Singh K, Casero RA, et al. Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction. PLoS One. 2011 Feb 28;6(2):e17510.
Barry, Daniel P., et al. “Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction.PLoS One, vol. 6, no. 2, Feb. 2011, p. e17510. Pubmed, doi:10.1371/journal.pone.0017510.
Barry DP, Asim M, Leiman DA, de Sablet T, Singh K, Casero RA, Chaturvedi R, Wilson KT. Difluoromethylornithine is a novel inhibitor of Helicobacter pylori growth, CagA translocation, and interleukin-8 induction. PLoS One. 2011 Feb 28;6(2):e17510.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

February 28, 2011

Volume

6

Issue

2

Start / End Page

e17510

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Protein Transport
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Interleukin-8
  • Humans
  • Helicobacter pylori
  • Helicobacter Infections
  • General Science & Technology