AUTHOR=Mucito-Varela Eduardo , Castillo-Rojas Gonzalo , Calva Juan J. , López-Vidal Yolanda 

TITLE=Integrative and Conjugative Elements of Helicobacter pylori Are Hypothetical Virulence Factors Associated With Gastric Cancer

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.525335

DOI=10.3389/fcimb.2020.525335

ISSN=2235-2988

ABSTRACT=<p><italic>Helicobacter pylori</italic> is a bacteria with high genome plasticity that has been associated with diverse gastric pathologies. The genetic diversity of this bacteria has limited the characterization of virulence factors associated with gastric cancer (GC). To identify potentially helpful disease biomarkers, we compared 38 complete genomes and 108 draft genomes of <italic>H. pylori</italic> isolated worldwide from patients with diverse gastric pathologies and 53 draft genomes of <italic>H. pylori</italic> isolated from Mexican patients with GC, intestinal metaplasia, gastritis, peptic ulcer, and dyspepsia. <italic>H. pylori</italic> strains isolated from GC were 3–11 times more likely to harbor any of seven genes encoded within an integrative and conjugative element (ICE) than <italic>H. pylori</italic> isolated from subjects with other gastric pathologies. We tested the cytopathic effects on AGS cells of selected <italic>H. pylori</italic> strains with known cytotoxin-associated gene pathogenicity island (<italic>cag</italic>-PAI) and ICE status (<italic>H. pylori</italic> strains 29CaP, 29CaCe, 62A9, 7C, 8822, and 26695) and the histopathological damage of <italic>H. pylori</italic> 29CaP and 62A9 in a mouse model. <italic>H. pylori</italic> 29CaP, which harbors a complete ICEHptfs3 but lacks <italic>cag</italic>-PAI, elicited distinctive morphology changes and higher histopathological scores compared with other <italic>H. pylori</italic> strains carrying <italic>cag</italic>-PAI and hybrid ICE with incomplete TFSS. The presence of intact segments of ICE regions might be a risk factor to develop GC that needs to be addressed in future studies.</p>