Copper Promotes TFF1-Mediated Helicobacter pylori Colonization

Montefusco, Sandro; Esposito, Roberta; D’Andrea, Luca Domenico; Monti, Maria Chiara; Dunne, Ciara; Dolan, Brendan; Tosco, Alessandra; Marzullo, Liberato; Clyne, Marguerite

doi:10.1371/journal.pone.0079455

Cited by 28 publications

(20 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…H. pylori is also capable of interacting with TFF3 dimer at >pH 7.0, but not with TFF2; even glycosylated TFF2 was shown not to interact with H. pylori (63, 125). The C-terminal of TFF1 can also specifically bind copper ions, which enhances H. pylori binding to TFF1 (126). However, MUC5AC is downregulated late in the gastric epithelium after H. pylori infection or ulceration (112, 127).…”

Section: Trefoil Factor and Gastrointestinal Diseasesmentioning

confidence: 99%

Trefoil Factor Peptides and Gastrointestinal Function

Aihara

Engevik²,

Montrose³

2017

Annu. Rev. Physiol.

153

135

View full text Add to dashboard Cite

Trefoil factor (TFF) peptides, containing a 40-amino acid motif, including six conserved cysteine residues that form intramolecular disulfide bonds, are a family of mucin-associated secretory molecules mediating many physiological roles that maintain and restore gastrointestinal (GI) mucosal homeostasis. TFF peptides play important roles in response to GI mucosal injury and inflammation. In response to acute GI mucosal injury, TFF peptides accelerate cell migration to seal the damaged area from luminal contents, whereas chronic inflammation leads to increased TFF expression to prevent further progression of disease. Although much evidence supports the physiological significance of TFF peptides in mucosal defenses, the molecular and cellular mechanisms of TFF peptides in the GI epithelium remain largely unknown. In this review, we summarize the functional roles of TFF1, 2, and 3 and illustrate their action mechanisms, focusing on defense mechanisms in the GI tract.

show abstract

Section: Trefoil Factor and Gastrointestinal Diseasesmentioning

confidence: 99%

Trefoil Factor Peptides and Gastrointestinal Function

Aihara

Engevik²,

Montrose³

2017

Annu. Rev. Physiol.

153

135

View full text Add to dashboard Cite

show abstract

“…Copper-mediated colonization of the stomach mucosa occurs through the action of trefoil peptides in H. pylori (Montefusco et al 2013) and copper drastically increases in cancerous tissues. However the detailed role of copA and copP genes and of copper metabolism in H. pylori long-term adaptation is yet to be investigated.…”

Section: Genes Involved In Heavy Metal Metabolismmentioning

confidence: 99%

Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori

et al. 2015

View full text Add to dashboard Cite

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipa) and hitherto unknown functional genes.KEYWORDS adaptation; neutral evolution; human pathogens H ELICOBACTER pylori is a Gram-negative bacterium that infects the mucosa of the human stomach. It was first described in the 1980s, when it was initially identified in association with chronic gastritis and later causally linked to serious gastric pathologies such as gastric cancer and ulcers (Marshall and Warren 1984;Suerbaum and Michetti 2002). It infects .80% of humans in developing countries and, although its prevalence is lower in developed countries, nearly 50% of the worldwide human population is infected (Ghose et al. 2005;Salih 2009;Salama et al. 2013).Due to its clinical and evolutionary importance, there has been considerable research on mechanisms of H. pylori transmission, as well as on the population genetics and phylogenetic relationships among global isolates. Thus far, population genetic analyses have mainly focused on seven housekeeping genes (usually referred to as multilocus sequence typing or MLST), with the primary conclusions being that H. pylori strains appear highly structured, and their phylogeographic patterns correlate consistently with that of their human hosts. Given that the H. pylori-humans association is at least 100,000 years old (Moodley et al. 2012), the current population structure of H. pylori may be regarded as mirroring past human expansions and migrations Linz et al. 2007;Breurec et al. 2011) and thus help us shed light on yet unknown dynamics of local demographic processes in human evolution. However, despite the knowledge gained thus far, the long-term global demographic history of H. pylori has never been directly inferred. The long, intimate association of H. pylori with humans suggests a history of bacterial adaptation. Considerable attention has focused on specific genes involved in modulating adaptive immunity of the host (for a review see Yamaoka 2010 andSalama et al. 2013) and on genomic changes occurring during acute and chronic H. pylori infection (Kennemann et al. 2011;Linz et a...

show abstract

“…Hence, the consequence of lost Piezo1 is sophisticated and depends on the origin of the tumour tissues. Montefusco et al [119] have reported that copper ions (Cu) promotes TFF1-mediated Hp colonization and Cu binding favours the homodimerization of TFF1 (Table 2), thus reinforcing its motogenic activity.…”

Section: Accepted Manuscriptmentioning

confidence: 99%