Pathogenesis of Helicobacter pylori Infection

Abstract

Helicobacter pylori relies on multiple colonization and virulence factors to persist in the human stomach for life. In addition, these factors can be modulated and vary to suit the ever-changing environment within the host individual. This article outlines the novel developments in this field of research during the past year, highlighting the cag pathogenicity island, VacA, c-glutamyl-transpeptidase as well as including recent advances in protein structure, bacteria-host interaction, and the role of stomach microbiota. Helicobacter pylori ColonizationIt is well established that flagella are essential for the motility of Helicobacter pylori and are particularly crucial at early stages of infection. In a recent study [1], seeking to learn more about the proteins that, as VacA, are secreted via the autotransporter (Type V) pathway, it has been demonstrated that one of the three VacA-like proteins, namely flagella-associated autotransporter A (FaaA), is enriched in the sheath covering the flagella filament and their terminal bulb, unlike the other two that localize on the surface of the bacteria. Interestingly, mutants lacking the faaA gene show a mislocalization of flagella, which also appear more fragile. This characteristic probably depends on the effect that FaaA exerts on the stability of the major flagellar protein FlaA that, despite an increased mRNA expression, is reduced in faaA deletion mutants. The latter show a reduced motility in vitro but, more importantly, a reduced ability in colonizing the stomach of mice [1].In conjunction with motility, bacterial shape is an important persistence factor. Recently, novel determinants for H. pylori cell shape, which, among others, depend on factors involved in peptidoglycan (PG) biosynthesis and degradation, were identified using a transposon mutagenesis-based approach coupled to flow cytometry [2]. Enriched clones contained insertions in known PG endopeptidases and novel genes involved in PG biosynthesis initiation and PG cleavage.A second step in colonization is supposed to be adherence. Earlier on, it had been reported that H. pylori can bind to trefoil factor 1 (TFF1), one of several peptides released during tissue trauma. Novel data on TFF1 now suggest that H. pylori binding to TFF1 dimer and to TFF1-overproducing gastric cells is dependent on copper availability in the environment [3]. It remains unclear how these in vitro findings translate to the in vivo situation in the human stomach.Similarly, further investigations are required to demonstrate the role in vivo of the recently identified twinarginine translocation system (Tat) of H. pylori [4]. In H. pylori, this system was predicted to be composed of three proteins, TatA, TatB, and TatC, and to permit the translocation of four substrates: the catalase accessory protein, KapA; the hydrogenase small-subunit protein HydA; a putative biotin sulfoxide reductase BisC; and the cytochrome oxidase Rieske subunit protein FbcF. tatB deletion was found to be compatible with H. pylori survival, while deletion o...

Meanders of an Atypical Research Work on Helicobacter pylori in the Democratic Republic of Congo: Influence of HIV and other Factors and Study of some Interesting Cases

“…(iv) A double intoxication then occurs, justifying numerous extradigestive pathologies described in Table 2. (v) This statement is in perfect harmony with recent literature which reports more and more extra-digestive pathologies linked to Helicobacter pylori [23,28,[35][36][37][38][39][40][41].…”

Helicobacter pyloritherapy: a paradigm shift

“…Because H. pylori associated gastric damage is progressive the ultimate effect of eradication depends on the degree of irreversible damage [1, 5-7]. …”

Polymorphisms in TLR9 but not in TLR5 increase the risk for duodenal ulcer and alter cytokine expression in the gastric mucosa

“…1,2 Microbial, host and environmental factors have been associated with the diverse clinical outcomes associated with H. pylori infection. 3 It has been shown that polymorphisms in genes of the inflammatory response, such as the pro-inflammatory cytokines IL-1b and TNF-a, increase the risk for gastric cancer in some populations but not in others.…”