Helicobacter pylori CagL Hypervariable Motif: A Global Analysis of Geographical Diversity and Association With Gastric Cancer.

Previous studies suggest overrepresentation of particular polymorphisms within the Helicobacter pylori CagL hypervariable motif (CagLHM) in gastric cancer-associated isolates. However, these disease correlations were geographically variable and ambiguous. We compared the disease correlation of several hundred geographically diverse CagL sequences and identified 33 CagLHM sequence combinations with disparate geographical distribution, revealing substantial worldwide CagLHM diversity, particularly within Asian countries. Notably, polymorphisms E59 and I60 were significantly overrepresented, whereas D58 and E62 were underrepresented, in gastric cancer-associated H. pylori isolates worldwide. Thus, CagLHM regional diversity may contribute to the varied prevalence of H. pylori-related gastric cancer observed in diverse populations.

Preservation of Helicobacter pylori CagA Translocation and Host Cell Proinflammatory Responses in the Face of CagL Hypervariability at Amino Acid Residues 58/59.

Carriage of the CagA oncoprotein by the human gastric cancer-associated pathogen Helicobacter pylori is significantly associated with this typically benign chronic infection advancing to a potentially fatal outcome. However it remains to be elucidated why only a small subset of individuals infected with H. pylori CagA-positive strains develops gastric cancer. H. pylori translocates CagA into host cells using a type IV secretion apparatus that interacts with host integrin receptors via a three-amino-acid-residue RGD motif on the H. pylori protein CagL. The RGD motif of CagL also plays a major role in the induction of proinflammatory responses. Upstream of this motif is a conserved glycine flanked by four hypervariable amino acid residues (residues 58, 59, 61 and 62). Certain amino acid polymorphisms at 58 and 59 are significantly prevalent in strains from gastric cancer patients in particular geographic regions; Y58E59 is seen in Taiwan and D58K59 in India. In light of the seemingly contradictory findings of recent CagL mutagenesis studies, we have examined the contribution of sequence promiscuity specifically at CagL residues 58 and 59 to CagA translocation and H. pylori-mediated proinflammatory responses of gastric epithelial cells. Using isogenic mutants of H. pylori strains P12 and 26695 with amino acid substitutions at CagL residues 58 and 59, we determined that carriage of the polymorphisms Y58E59, D58K59, D58E59, N58E59 or N58K59 did not significantly alter the capacity of H. pylori to translocate CagA into, or induce IL-8 secretion in, host cells. Our findings, together with other recently published data, suggest that the variation at CagL residues 58 and 59 does not influence type IV secretion system function in isolation, but rather may work in concert with particular polymorphisms elsewhere in CagL to modulate disease progression.

Unsaturated fatty acids from food and in the growth medium improve growth of Bacillus cereus under cold and anaerobic conditions.

In a chemically defined medium and in Luria broth, cold strongly reduced maximal population density of Bacillus cereus ATCC 14579 in anaerobiosis and caused formation of filaments. In cooked spinach, maximal population density of B. cereus in anaerobiosis was the same at cold and optimal temperatures, with normal cell divisions. The lipid containing fraction of spinach, but not the hydrophilic fraction, restored growth of B. cereus under cold and anaerobiosis when added to the chemically defined medium. This fraction was rich in unsaturated, low melting point fatty acids. Addition of phosphatidylcholine containing unsaturated, low melting point, fatty acids similarly improved B. cereus anaerobic growth at cold temperature. Addition of hydrogenated phosphatidylcholine containing saturated, high melting point, fatty acids did not modify growth. Fatty acids from phospholipids, from spinach and from hydrogenated phosphatidylcholine, although normally very rare in B. cereus, were inserted in the bacterium membrane. Addition of phospholipids rich in unsaturated fatty acids to cold and anaerobic cultures, increased fluidity of B. cereus membrane lipids, to the same level as those from B. cereus normally cold adapted, i.e. grown aerobically at 15 °C. B. cereus is therefore able to use external fatty acids from foods or from the growth medium to adapt its membrane to cold temperature under anaerobiosis, and to recover the maximal population density achieved at optimal temperature.