Targeting of Mammalian Glycans Enhances Phage Predation in the Gastrointestinal Tract

• Type of Material: Article
• Authors: Sabrina I. Green, Baylor College of Medicine; Carmen Gu Liu, Baylor College of Medicine; Xue Yu, Baylor College of Medicine; Shelley Gibson, Baylor College of Medicine; Wilhem Salmen, Baylor College of Medicine; Anubama Rajan, Baylor College of Medicine; Hannah E. Carter, Baylor College of Medicine; Justin R. Clark, Baylor College of Medicine; Xuezheng Song, Emory University; Robert F. Ramig, Baylor College of Medicine; Barbara W. Trautner, Michael E DeBakey VA Medical Center; Heidi B. Kaplan, University of Texas; Anthony W. Maresso, Baylor College of Medicine
• Language: English
• Date: 2021-01-01
• Publisher: American Society of Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Green et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/mBio.03474-20
• Title of Journal or Parent Work: mBio
• Volume: 12
• Issue: 1
• Start Page: 1
• End Page: 18
• Grant/Funding Information: This work is supported in part by grant from US Veterans Affairs (VA I01-RX002595), Roderick D. MacDonald Research Fund at Baylor St. Luke’s Medical Center, the Mike Hogg Foundation, and seed funds from Baylor College of Medicine Seed Fund.; Imaging for this project was supported by the Integrated Microscopy Core at Baylor College of Medicine with funding from NIH (DK56338, and CA125123), CPRIT (RP150578, RP170719), the Dan L. Duncan Comprehensive Cancer Center, and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.
• Keywords: bacteriophages; multidrug resistance; Microbiome; Mucus; Microbiology; Bacteriophage; pathobiont; New model; Life Sciences & Biomedicine; Science & Technology; Mucin; bacteriophage therapy; Protein; Specificity; E. coli; pathogens; Polyssacharide
• Research Categories: Biology, Microbiology; Biology, Genetics; Chemistry, Biochemistry

Abstract

The human gastrointestinal mucosal surface consists of a eukaryotic epi-thelium, a prokaryotic microbiota, and a carbohydrate-rich interface that separates them. In the gastrointestinal tract, the interaction of bacteriophages (phages) and their prokaryotic hosts influences the health of the mammalian host, especially colonization with invasive pathobionts. Antibiotics may be used, but they also kill protective commensals. Here, we report a novel phage whose lytic cycle is enhanced in intestinal environments. The tail fiber gene, whose protein product binds human heparan sulfated proteoglycans and localizes the phage to the epithelial cell sur-face, positions it near its bacterial host, a type of locational targeting mechanism. This finding offers the prospect of developing mucosal targeting phage to selec-tively remove invasive pathobiont species from mucosal surfaces.