Enteroaggregative E. coli Adherence to Human Heparan Sulfate Proteoglycans Drives Segment and Host Specific Responses to Infection.

Autor: Rajan A; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Robertson MJ; Molecular and Cell Biology-Mol. Regulation, Baylor College of Medicine, Houston, TX, United States of America., Carter HE; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Poole NM; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Clark JR; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Green SI; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Criss ZK; Department of Medicine Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States of America., Zhao B; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States of America., Karandikar U; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Xing Y; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Margalef-Català M; Department of Pediatrics, Division of Infectious Diseases, Stanford University, Stanford, CA, United States of America., Jain N; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States of America., Wilson RL; Department of Bioengineering, Rice University, Houston, TX, United States of America., Bai F; Department of Biochemistry, Emory Comprehensive Glycomics Core, Emory University School of Medicine, Atlanta, GA, United States of America., Hyser JM; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Petrosino J; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Shroyer NF; Department of Medicine Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States of America., Blutt SE; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Coarfa C; Molecular and Cell Biology-Mol. Regulation, Baylor College of Medicine, Houston, TX, United States of America.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, United States of America., Song X; Department of Biochemistry, Emory Comprehensive Glycomics Core, Emory University School of Medicine, Atlanta, GA, United States of America., Prasad BV; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, United States of America., Amieva MR; Department of Pediatrics, Division of Infectious Diseases, Stanford University, Stanford, CA, United States of America., Grande-Allen J; Department of Bioengineering, Rice University, Houston, TX, United States of America., Estes MK; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America., Okhuysen PC; Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America., Maresso AW; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2020 Sep 28; Vol. 16 (9), pp. e1008851. Date of Electronic Publication: 2020 Sep 28 (Print Publication: 2020).
DOI: 10.1371/journal.ppat.1008851
Abstrakt: Enteroaggregative Escherichia coli (EAEC) is a significant cause of acute and chronic diarrhea, foodborne outbreaks, infections of the immunocompromised, and growth stunting in children in developing nations. There is no vaccine and resistance to antibiotics is rising. Unlike related E. coli pathotypes that are often associated with acute bouts of infection, EAEC is associated with persistent diarrhea and subclinical long-term colonization. Several secreted virulence factors have been associated with EAEC pathogenesis and linked to disease in humans, less certain are the molecular drivers of adherence to the intestinal mucosa. We previously established human intestinal enteroids (HIEs) as a model system to study host-EAEC interactions and aggregative adherence fimbriae A (AafA) as a major driver of EAEC adherence to HIEs. Here, we report a large-scale assessment of the host response to EAEC adherence from all four segments of the intestine across at least three donor lines for five E. coli pathotypes. The data demonstrate that the host response in the duodenum is driven largely by the infecting pathotype, whereas the response in the colon diverges in a patient-specific manner. Major pathways altered in gene expression in each of the four enteroid segments differed dramatically, with responses observed for inflammation, apoptosis and an overwhelming response to different mucin genes. In particular, EAEC both associated with large mucus droplets and specific mucins at the epithelial surface, binding that was ameliorated when mucins were removed, a process dependent on AafA. Pan-screening for glycans for binding to purified AafA identified the human ligand as heparan sulfate proteoglycans (HSPGs). Removal of HSPG abrogated EAEC association with HIEs. These results may mean that the human intestine responds remarkably different to distinct pathobionts that is dependent on the both the individual and intestinal segment in question, and uncover a major role for surface heparan sulfate proteoglycans as tropism-driving factor in adherence and/or colonization.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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