Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters

Jeremy J. Barr, Rita Auro, Nicholas Sam-Soon, Sam Kassegne, Gregory Peters, Natasha Bonilla, Mark Hatay, Sarah Mourtada, Barbara Bailey, Merry Youle, Ben Felts, Arlette Baljon, Jim Nulton, Peter Salamon, Forest Rohwer

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81 Citations (Scopus)


Bacteriophages (phages) defend mucosal surfaces against bacterial infections. However, their complex interactions with their bacterial hosts and with the mucus-covered epithelium remain mostly unexplored. Our previous work demonstrated that T4 phage with Hoc proteins exposed on their capsid adhered to mucin glycoproteins and protected mucus-producing tissue culture cells in vitro. On this basis, we proposed our bacteriophage adherence to mucus (BAM) model of immunity. Here, to test this model, we developed a microfluidic device (chip) that emulates a mucosal surface experiencing constant fluid flow and mucin secretion dynamics. Using mucus-producing human cells and Escherichia coli in the chip, we observed similar accumulation and persistence of mucus-adherent T4 phage and nonadherent T4Δhoc phage in the mucus. Nevertheless, T4 phage reduced bacterial colonization of the epithelium >4,000-fold compared with T4Δhoc phage. This suggests that phage adherence to mucus increases encounters with bacterial hosts by some other mechanism. Phages are traditionally thought to be completely dependent on normal diffusion, driven by random Brownian motion, for host contact. We demonstrated that T4 phage particles displayed subdiffusive motion in mucus, whereas T4Δhoc particles displayed normal diffusion. Experiments and modeling indicate that subdiffusive motion increases phage-host encounters when bacterial concentration is low. By concentrating phages in an optimal mucus zone, subdiffusion increases their host encounters and antimicrobial action. Our revised BAM model proposes that the fundamental mechanism of mucosal immunity is subdiffusion resulting from adherence to mucus. These findings suggest intriguing possibilities for engineering phages to manipulate and personalize the mucosal microbiome.
Original languageEnglish
Pages (from-to)13675-13680
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number44
Publication statusPublished - 3 Nov 2015
Externally publishedYes


  • BAM
  • Mucus
  • Search strategy
  • Subdiffusion
  • Virus

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