CagY-Dependent Regulation of Type IV Secretion in Helicobacter pylori Is Associated with Alterations in Integrin Binding

MBio
Emma C SkoogJay V Solnick

Abstract

Strains of Helicobacter pylori that cause ulcer or gastric cancer typically express a type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI). CagY is an ortholog of VirB10 that, unlike other VirB10 orthologs, has a large middle repeat region (MRR) with extensive repetitive sequence motifs, which undergo CD4+ T cell-dependent recombination during infection of mice. Recombination in the CagY MRR reduces T4SS function, diminishes the host inflammatory response, and enables the bacteria to colonize at a higher density. Since CagY is known to bind human α5β1 integrin, we tested the hypothesis that recombination in the CagY MRR regulates T4SS function by modulating binding to α5β1 integrin. Using a cell-free microfluidic assay, we found that H. pylori binding to α5β1 integrin under shear flow is dependent on the CagY MRR, but independent of the presence of the T4SS pili, which are only formed when H. pylori is in contact with host cells. Similarly, expression of CagY in the absence of other T4SS genes was necessary and sufficient for whole bacterial cell binding to α5β1 integrin. Bacteria with variant cagY alleles that reduced T4SS function showed comparable reduction in binding to α5β1 integrin, although Ca...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Microbiology·Maria Felicia SoluriClelia Peano
May 16, 2020·Gastroenterology Research and Practice·Qingbin NiuBaoguang Hu
Feb 26, 2019·Proceedings of the National Academy of Sciences of the United States of America·Johanna C SierraKeith T Wilson
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Oct 15, 2020·International Journal of Molecular Sciences·Shamshul Ansari, Yoshio Yamaoka
Feb 26, 2021·The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien Des Maladies Infectieuses Et De La Microbiologie Médicale·Manouchehr Ahmadi Hedayati, Saeed Salavati

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Methods Mentioned

BETA
flow cytometry
scanning electron microscopy
scanning
electron microscopy
two-hybrid
immunoprecipitation
surface plasmon resonance
PCR
fluorescence microscopy
electrophoresis

Software Mentioned

GraphPad Prism
GraphPad
NIS Elements
ImageJ

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