Barr Lab

Research Areas

The BAM model

The bacteriophage adherence to mucus (BAM) model provides a ubiquitous, but non-host-derived, immunity mediated by phages that is applicable to all mucosal surfaces. Both bacteria and phages are closely associated with mucus. Yet phage-to-bacteria ratios in mucus were increased, relative to the adjacent environment, in animals ranging from cnidarians to humans. In vitro studies demonstrated that this increase in phage abundance is mucus-dependent and protects the underlying cellular epithelium from bacterial infection.

Phage enrichment in mucus occurs via weak binding interactions between mucus and mucus-adherence protein domains displayed on phage capsids. Specifically, phage capsid immunoglobulin-like (Ig-like) domains bound the variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like domains are present in phages from diverse environments, and are increased in locations associated with mucus.

The BAM model has unexplored implications across diverse animal-associated mucosal surfaces, offering an astounding potential of diversity and specificity. We are continuing to investigate the role of the BAM model across diverse experimental systems, with a particular focus on the gut.

For more information, see "Bacteriophage adhering to mucus provide a non-host-derived immunity."

Download the PDF here.

 

At the most basic level, bacteriophage are nothing more than inanimate protein shells designed to carry genetic information through an environment. Being inanimate, phages must rely upon diffusion (or Brownian motion) in order to move through an environment and eventually encounter a bacterial host. Yet when placed in a mucus environment, mucus-adherent phages exhibited subdiffusive motion, not normal diffusion. Subdiffusion is a complex bio-physical process whereby a particle does not diffuse with a linear relationship to time. Simply put, the distance a subdiffusive particle drifts becomes less and less as time progresses.

Subdiffusive motion of phages in mucus acted to concentrate the phage particles within a specific region of the mucosal layer. Supporting theory and experiments revealed subdiffusion in mucus actually enhanced the chance of a phage successfully infecting a bacteria host and increased antimicrobial action. Our research proposes that the BAM models fundamental mechanism is subdiffusion resulting from phage adherence to mucus.

The search for a specific target is a ubiquitous process throughout biology. At the microscopic scale, molecules and enzymes perform site-specific searches within a cell; at the macroscopic scale, animals search for food. Many of these predators can see or smell their prey. But for phages, their search for a bacterial host to infect is effectively ‘blind’. When limited to blind, random searches, the chance of a successful encounter largely depends on the search strategy employed. Our research shows that mucus-adherent phage use a subdiffusive search strategy to effectively ‘hunt’ bacteria in mucus. We are continuing to investigate the subdiffusive dynamics of a variety of phages and their respective mucus-adherence domains in mucosal surfaces.

For more information, see "Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters."

Download the PDF here.

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Barr Laboratory | Monash University Feedback/Questions

Location
Monash University
School of Biological Sciences
Senior Zoology
Clayton VIC 3168
Australia

Contact Info
Email: jeremybarr85@gmail.com