Identification of self-growth-inhibiting compounds lauric acid and 7-(Z)-tetradecenoic acid from Helicobacter pylori

Abstract

Helicobacter pylori growth medium is usually supplemented with horse serum (HS) or FCS. However, cyclodextrin derivatives or activated charcoal can replace serum. In this study, we purified self-growth-inhibiting (SGI) compounds from H. pylori growth medium. The compounds were recovered from porous resin, Diaion HP-20, which was added to the H. pylori growth medium instead of known supplements. These SGI compounds were also identified from 2,6-di-O-methyl-b-cyclodextrin, which was supplemented in a pleuropneumonia-like organisms broth. The growth-inhibiting compounds were identified as lauric acid (LA) and 7-(Z)-tetradecenoic acid [7-(Z)-TDA]. Although several fatty acids had been identified in H. pylori, these specific compounds were not previously found in this species. However, we confirmed that these fatty acids were universally present in the cultivation medium of the H. pylori strains examined in this study. A live/dead assay carried out without HS indicated that these compounds were bacteriostatic; however, no significant growth-inhibiting effect was observed against other tested bacterial species that constituted the indigenous bacterial flora. These findings suggested that LA and 7-(Z)-TDA might play important roles in the survival of H. pylori in human stomach epithelial cells.

Potential Role of Biofilm Formation in the Development of Digestive Tract Cancer With Special Reference to Helicobacter pylori Infection

“…One well-characterized DSF is 2-(Z)-tetradecenoic acid (TDA) produced by the xylem-limited plant pathogen Xylella fastidiosa (Ryan and Dow, 2011; Ryan et al, 2015). Recently, Yamashita et al reported two self-growth-inhibiting compounds in Hp and one of them was identified as 7-(Z)-TDA (Yamashita et al, 2015). Although it has not been reported as a DSF, 2-(Z)-TDA is a positional isomer of 7-(Z)-TDA.…”

In Vitro and In Vivo Activities of Zinc Linolenate, a Selective Antibacterial Agent against Helicobacter pylori

“…A number of free fatty acids (FFAs), with potent antibacterial activities against a broad range of bacteria (18)(19)(20)(21), including H. pylori, are of considerable research interests. In particular, FFAs seem to induce no acquired resistance to the antibacterial effect and are considered safe, which make them attractive as antibacterial agents for commercial exploitation.…”

A proposed role for diffusible signal factors in the biofilm formation and morphological transformation of Helicobacter pylori

“…There is currently no evidence for the ability of TDA to be able to activate gene expression, and it is assumed that only cis-2-unsaturated acids (C x :Δ 2 ) has such activity (34,44). The studies conducted by Ionescu et al (38) showed that in X. fastidiosa cis-2-tetradecenic acid (C 14 :Δ 2 , XfDSF) and cis-2-hexadecenic acid (C 16 :Δ 2 , XfDSF2) are the strongest gene expression activators.…”

“…autoaggregative behavior and biofilm formation (35,38,39,45,46). Reduction of DSFs activity and an increase in AI-2 concentration results in the transformation of some coccoid H. pylori forms to the spiral morphotype, followed by chemorepulsion from the AI-2 source and migration in search of new niches in the gastric environment (6,17,(30)(31)(32)44).…”

“…Cis-2-tetradecenic acid (C 14 :Δ 2 ), which is produced by X. fastidiosa, is responsible for biofilm formation and autoaggregative behavior associated with the increased synthesis of hemagglutinin-like HxfA/B proteins. This compound is a positional isomer of TDA (C 14 :Δ 7 ) produced by H. pylori (44).…”