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Identification and characterization of a vitamin D? decomposition product bactericidal against Helicobacter pylori.

ABSTRACT: This study demonstrated that the vitamin D? decomposition product VDP1 exerts an antibacterial action against Helicobacter pylori but not against other bacteria. Treatment with VDP1 induced a collapse of cell membrane structures of H. pylori and ultimately lysed the bacterial cells. A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells. In separate experiments, VDP1 had no influence on the viability of the human cancer cell lines MKN45 and T47D and lacked any vitamin D?-like hormonal action against the latter. In both (1)H and (13)C NMR analyses, the spectra patterns of VDP1 corresponded with those of Grundmann's ketone. These results suggest that VDP1 (or Grundmann's ketone-type indene compound) may become a fundamental structure for the development of new antibacterial substances with selective bactericidal action against H. pylori.

SUBMITTER: Hosoda K

PROVIDER: S-EPMC4352922 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Identification and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori.

Hosoda Kouichi K Shimomura Hirofumi H Wanibuchi Kiyofumi K Masui Hisashi H Amgalanbaatar Avarzed A Hayashi Shunji S Takahashi Takashi T Hirai Yoshikazu Y

Scientific reports 20150309

This study demonstrated that the vitamin D₃ decomposition product VDP1 exerts an antibacterial action against Helicobacter pylori but not against other bacteria. Treatment with VDP1 induced a collapse of cell membrane structures of H. pylori and ultimately lysed the bacterial cells. A unique dimyristoyl phosphatidylethanolamine in the membrane lipid compositions contributed to the interaction of VDP1 with H. pylori cells. In separate experiments, VDP1 had no influence on the viability of the hum ...[more]

PMID: 25749128

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Project description:The most evident challenge to treatment of Helicobacter pylori, a bacterium responsible for gastritis, peptic ulcers and gastric cancer, is the increasing rate of resistance to all currently used therapeutic antibiotics. Thus, the development of novel therapies is urgently required. N-geranyl-N'-(2-adamantyl) ethane-1, 2-diamine (SQ109) is an ethylene diamine-based antitubercular drug that is currently in clinical trials for the treatment of tuberculosis (TB). Previous pharmacokinetic studies of SQ109 revealed that persistently high concentrations of SQ109 remain in the stomach 4 hours post oral administration in rats. This finding, combined with the need for new anti-Helicobacter therapies, prompted us to define the in vitro efficacy of SQ109 against H. pylori. Liquid broth micro-dilution was used for susceptibility studies to determine the antimicrobial activity of SQ109 against a total of 6 laboratory strains and 20 clinical isolates of H. pylori; the clinical isolates included a multi-drug resistant strain. All strains tested were susceptible to SQ109 with MIC and MBC ranges of 6-10 µM and 50-60 µM, respectively. SQ109 killing kinetics were concentration- and time-dependent. SQ109 killed H. pylori in 8-10 h at 140 µM (2MBCs) or 4-6 h at 200 µM (~3MBCs). Importantly, though the kinetics of killing were altered, SQ109 retained potent bactericidal activity against H. pylori at low pH. Additionally, SQ109 demonstrated robust thermal stability and was effective at killing slow growing or static bacteria. In fact, pretreatment of cultures with a bacteriostatic concentration of chloramphenicol (Cm) synergized the effects of typically bacteriostatic concentrations of SQ109 to the level of five-logs of bacterial killing. A molar-to-molar comparison of the efficacy of SQ109 as compared to metronidazole (MTZ), amoxicillin (AMX), rifampicin (RIF) and clarithromycin (CLR), revealed that SQ109 was superior to MTZ, AMX and RIF but not to CLR. Finally, the frequency of resistance to SQ109 was low and electron microscopy studies revealed that SQ109 interacted with bacterial inner membrane and cytoplasmic content(s). Collectively, our in vitro data demonstrate that SQ109 is an effective monotherapy against susceptible and multi-drug resistant strains of H. pylori and may be useful alone or in combination with other antibiotics for development as a new class of anti-Helicobacter drugs.

Dataset Information

Identification and characterization of a vitamin D? decomposition product bactericidal against Helicobacter pylori.

Publications

Identification and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori.

Similar Datasets

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