Bacteriophages may protect us against pathogens

Posted by Kasra

Given the extremely large amount of bacteria in our gastrointestinal track, it is not surprising to think that the gut would be also swarming with pathogens of bacteria, that is bacteriophages as well. In their recent work published in PNAS, Barr et al. take a look at what impact these particles could have on the population of bacteria in mucosal surfaces and what could it mean for us. Their work actually turns out very interesting results.

Mucosal surfaces are the body’s points of contact  with the outside. Being highly populated with bacteria, they can be suitable points of infection as well. That is why they are heavily guarded with various immune barriers and mechanisms, both innate and adaptive. Barr et al. point to a possible mechanism of protection against infection which not innate nor adaptive. They start by comparing the amounts of bacteria and bacteriophages in different mucosal and non-mucosal surfaces in various mucus producing animals. They interestingly observe that the bacteriophage to bacteria ratio in mucosal sites is way larger than those in adjacent non-mucosal sites (from average about 40fold to average about 3fold). They verify this in both invertebrates and vertebrates and thus suggest that this could be a phenomenon in all mucus-producing metazoans.

Next, they point to a previous recent study by Minot et al. who had found immunoglobulin (Ig)-like domains in the total analyzed genome of human gut viruses (or so called human gut virome).  These domains that usually act as in recognition and binding (as an antibody would do); they show that the bacteriophages actually bind to mucus through these proteins.  Barr et al. also show that presence of bacteriophages on a mucosal surface significantly reduces Escherichia coli invasion in vitro.


Model for how presence of bacteriophage on the mucosal surface can help in protection against bacterial infection. From Barr et al. PNAS 2013 PMID: 23690590

This is an incredible system where the benefit of the bacteriophages and their hosts actually match. It is not clear at this point whether the animal body would have to do something other than producing mucus to keep the bacteriophages where they are or that it is just enjoying this protection more or less free of charge.

Barr JJ, Auro R, Furlan M, Whiteson KL, Erb ML, Pogliano J, Stotland A, Wolkowicz R, Cutting AS, Doran KS, Salamon P, Youle M, & Rohwer F (2013). Bacteriophage adhering to mucus provide a non-host-derived immunity. Proceedings of the National Academy of Sciences of the United States of America PMID: 23690590

Minot S, Grunberg S, Wu GD, Lewis JD, & Bushman FD (2012). Hypervariable loci in the human gut virome. Proceedings of the National Academy of Sciences of the United States of America, 109 (10), 3962-6 PMID: 22355105

Degradation of the intestinal mucus barrier by whipworm

Posted by: Kasra

I wrote recently about modulation of the host by intestinal worm Trichuris muris. Here is another brilliant study looking at the secreted proteins of this nematode and how they interact with the small intestine mucus.

 Hasnain et al. published in PLoS NTD that secreted proteins of T. muris contain serine proteases that are able to degrade the mucus barrier, especially Muc2. Interestingly, they observed that the components of the mucus barrier are different during acute versus chronic infection. When worm expulsion begins in acute infection of T. muris, Muc5a is also detected in the mucus, a protein which is normally not expressed in the intestinal mucus but in the lung. Muc5a is resistant to degradation by serine proteases of the parasite and probably helps in worm expulsion. This specific host response and change in mucus does not happen during chronic infection which results in continued stay of the worm in the intestine.

Secreted Proteins of T. muris degrade the mucus in chronic but not acute infection. This is due to upregulation of Muc5a in acute infection, which is resistant to the proteases. From Hasnain et al. PLoS NTD, doi:10.1371/journal.pntd.0001856.g003

Below is a schematic diagram of the structure of the mucus layer during acute and chronic infection and how Excreted Secreted Proteins (ESPs) of the parasite interact with it.

A schematic of how the mucus layer looks like during acute or chronic infection with T. muris. From Hasnain et al. PLoS NTD doi:10.1371/journal.pntd.0001856.g003

Hasnain SZ, McGuckin MA, Grencis RK, & Thornton DJ (2012). Serine Protease(s) Secreted by the Nematode Trichuris muris Degrade the Mucus Barrier. PLoS neglected tropical diseases, 6 (10) PMID: 23071854