title: Bacteriophage adhering to mucus provide a non-host-derived immunity.
abstract: Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non-host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage coevolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces.
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182, USA. jeremybarr85@gmail.com
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Barr
authors.forename: Rita
authors.initials: R
authors.lastname: Auro
authors.forename: Mike
authors.initials: M
authors.lastname: Furlan
authors.forename: Katrine L
authors.initials: KL
authors.lastname: Whiteson
authors.forename: Marcella L
authors.initials: ML
authors.lastname: Erb
authors.forename: Joe
authors.initials: J
authors.lastname: Pogliano
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Stotland
authors.forename: Roland
authors.initials: R
authors.lastname: Wolkowicz
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Cutting
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Doran
authors.forename: Peter
authors.initials: P
authors.lastname: Salamon
authors.forename: Merry
authors.initials: M
authors.lastname: Youle
authors.forename: Forest
authors.initials: F
authors.lastname: Rohwer
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology; D017122:Bacteriophage T4 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D001435:Bacteriophages / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D002460:Cell Line; D004926:Escherichia coli / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D009093:Mucus / Q000276:immunology* / Q000382:microbiology / Q000821:virology*; D013559:Symbiosis / Q000276:immunology
keywords: host-pathogen; immune system; immunoglobulin; symbiosis; virus