We’ve known for a long time that there are good bacteria and bad bacteria. Now, we’re coming to realize there are also good viruses and bad viruses. The good viruses — good for us, that is — are viruses that infect and kill bacteria. These viruses are called bacteriophage or phage. It turns out that, indeed, animals may use phage as weapons against bad bacteria (bacterial pathogens) at a strategic location, the mucosal surfaces.
Mucosal surfaces are mostly out of sight, but are present all throughout the body and line the respiratory, gastrointestinal, and urogenital tracts, as well as glands — for example lachrymal glands, salivary glands and mammary glands of the lactating breast.
Mucosal surfaces are covered with mucus — a sticky layer that serves as a protective barrier at the interface between the environment and animal tissues. It is the mucus that traps the phage, so the phage are kept in the mucus to destroy bacterial pathogens before they can actually reach the tissues and potentially cause infection. The mucus, then, provides the stage for a unique form of symbiosis between animals and viruses. How?
To understand the answer to this question, it is important to note that phage have mostly one thing in mind — reproduction. In order to reproduce, phage multiply inside bacteria and disintegrate them in order to exit and infect more bacteria. In other words, the process of phage reproduction leads to bacterial death. Thus, phage help us control bacterial pathogens while, at the same time, helping themselves to flourish.
Jeremy Barr (San Diego State University) and his collaborators propose a detailed model to explain how mucus traps phage for protection against bacteria. The model, backed up by convincing experimental evidence, is presented in a paper published in Proc Natl Acad Sci USA (June 25, 2013 — Bacteriophage adhering to mucus provide a non–host-derived immunity).
First, the researchers demonstrated that mucus is phage-enriched compared with the surrounding environment. This finding proved true in all samples of mucus layers tested, which included coral, fish and human samples. Second, they showed that the majority of phage in mucosal samples contain specialized protein structures called Ig-like domains. These findings provided the basic information to develop the model, which was then built on additional experimental observations (see below).
Phage consist of one head and one tail. The head, which serves as a protective covering for the genetic material, is composed of many copies of one or more different proteins. The tail is a hollow tube that allows binding and transfer of the phage’s genetic material to bacteria.
The researchers used an experimental model consisting of human cells in culture, the bacterial pathogen Escherichia coli, and the bacteriophage T4 to show that the phage is not only viable and able to reproduce when trapped in mucus, but also able to
efficiently kill E. coli. Furthermore, T4 trapped in mucus protected human cells in culture from death caused by E. coli. The researchers also carried out experiments showing that the mucus-phage interaction is mediated by glycans contained in the mucus glycoprotein and by Ig-like domains of the phage head proteins.
According to the general lines of the model, then, mucus and phages interact with each other, Velcro-style, through the binding of two specialized structures — a mucus glycoprotein and proteins containing Ig-like domains on the phage head. The phage becomes embedded headfirst into the mucus, while the tail mediates infection and killing of the invading bacteria.
The model opens up intriguing new concepts and possibilities — for example, the mucus-phage interaction may represent an integral and previously unrecognized component of innate immune responses in a large variety of animals, including humans. In addition, phage able to kill specific pathogens could be used to coat mucosal surfaces in novel therapeutic approaches.
Copyright © 2014 Immunity Tales.
Great article! I think the breakthrough uses of phage therapy has introduced us to the next generation of protection from deadly pathogens. The very idea that scientists can manipulate viruses into ridding our bodies of deadly pathogens is, unfortunately, not yet acceptable in the United States. However, with the rise in antibiotic-resistant bacteria, such as MRSA, hopefully researchers will approve phage therapy for public use.
Is the idea acceptable in other countries? Please clarify your topic of discussion – it should be related to innate immunity and the discovery of new components of it.
I believe the major aspect of phage therapy preventing its commercial use that Americans clench at the concept of phage, or viruses, being injected into their bodies. Although it was mentioned in the final paragraph of the article, I also wanted to mention how the concept bacteriophage can impact the innate immune defenses. The article claims that these phages can be found in mucosal areas, such as the respiratory tract, gastrointestinal tract, urogenital tract. These are three of the most common sites of pathogenic infections. If scientists were capable of controlling this phage, the innate immunity might be able to combat pathogens more easily. According to the article, researchers might also be able to insert bacteria-specific phage on to a certain mucosal surface. This would be useful in case an infection with that specific bacteria were to occur.
It was really interesting to see the relationship with the phage and the mucus. It is also really refreshing because I feel like bacteriophages will able to create more positive stereotypes about viruses. These bacteriophages would do wonders if they were able to become mainstream in America. Phages were first found as an antibacterial agent by Frederick Twort and Felix d’Herelle and are great because they will only infect bacteria cells but not animal, plant, or human cells. Phages are easier to create than antibiotics and phages are cheaper to make as well. Hopefully phages can be the answer to the growing ineffective antibiotics problems.
I thought we were discussing innate immunity….
It is great to see that we have other options when dealing with bacterial infections. A down side to these bacteriophages is that they are very specific about what receptors they attach to, so there would have to be many bacteriophages to keep up with the variety of bacteria. I hate to see that this has not made it to America but financially i would think the pharmaceutical companies would be the ones to fund this, and why would they fund something that they really cant “claim” as their own?
What is this story about not having made it to America? What is that should be making it to America??????
It doesn’t mention anything about being used in America, and when I say it I am referring to the use of bacteriophages (inside the human body) to fight against bacteria infections. Most studies have been done in the former Soviet Union and Eastern Europe but not here in America. Another thing to consider would be the fact that we could get away from using antibiotics as much as we do by replacing them with bacteriophages. Wouldn’t that be nice? We wouldn’t have to take a pill for every infection that we were diagnosed with and this also helps the people that are resistant to certain antibiotics.
Please note the post discusses innate immunity and the role of phages in innate immunity. What is this story about the use of phages here or somewhere else? How is it connected to innate immunity?
In regards to the innate immunity, I think that the mucus is a great place for the bacteriophage to be localized or have a connection ( the mucus-phage interaction). These layers are sometimes found under the epithelial cells where breaks in the skin allow microbes to penetrate. These layers will then be the first place that our body will have to defend us. Since the innate immunity is the first to respond their will be a connection with the bacteriophages and the innate immunity working together to clear the infections. Mucus layers typically harbor many different microbes that hang around in these layers. This is ideal for bacteriophages as it gives them the ability to perform their selective microbial killing within the mucus environments and if they have the ability to adhere to the mucus than they will be around longer and will have greater numbers compared to the microbes.
Nature has a way of controlling populations, from predator-prey interactions to competition. Bacteriophages is just one of nature’s way for controlling bacterial populations and it’s convenient for us because some bacteriophages inhabit our mucosal linings. It is interesting that nature has presented this mucus-phage interaction and evolution has favored it. If more research was conducted to better understand the chemical bonds within the mucus-phage interaction, we could extend those findings towards helping immunocompromised patients. After understanding the chemical components behind the mucus-phage interaction, it can then be enhanced. Afterwards, these phages could be used in tangent with the innate immune system to prevent and possibly treat bacterial infections in these patients.
This article is very interesting to say the least. I thought all viruses were “bad” when it came to them being inside the body. Its fantastic that the human body can form a symbiotic relationship with something that usually causes bodily harm. Does anybody know exactly why this is not acceptable in the United States? What are the negative outcomes of this process if there are any?
What is the process you’re talking about? What is that is not acceptable in the United States?
Sorry I misunderstood, I thought this process of the virus forming a symbiotic relationship with the body was induced only by scientific experimentation. I now know this is a naturally occurring process. However when I asked why is this not yet acceptable in America I was asking a question stemming from the comment Jonathan Rosenthal made about this not yet being accepted in the United States.
Bacteriophages do not directly cause “bodily harm” because they invade and reproduce inside bacteria cells, not human cells. The bacterial cell lyses, releasing replicated bacteriophages that are ready to infect other bacteria cells. The only way bacteriophages can technically harm humans is by infecting bacteria that are part of our normal flora. Depletion of the normal flora allows for other bacteria to survive and reproduce since bacteriophages have eliminated the competing bacteria. This becomes a bacterial infection.
While it is very engrossing to find that viruses are more than simply bad I am still curious as to what happens after long periods of these viruses inhabiting the human body. Is it possible for adverse effects to occur after long periods of time? Also another interesting thought I had was if it were possible for these phages to prevent other viruses from establishing themselves in our body. Much similar to how harmless bacteria that occupies our skin or intestines, for example, prevents potentially virulent bacteria from causing us harm. Nonetheless more studies done with interaction of phages and human mucosal linings and the bacteria will reveal more information which could potentially lead to medical breakthroughs to help us fight against viruses like HIV/AIDS. We would be able to fight fire with fire. This discovery is nothing short of exciting and provides a new light on how we can approach preventative medicine with our immune system.
This is a truely fascinating discovery. I can only imagine the possibilities of using a phaged-enriched mucus to fight against pathogens that our human bodies may encounter. Because they are bacteriophages, these viruses will only attack bacteria, and so our humans cells are never at harm. This also mean that there is probably no interaction between the phage and the humans cells, which also means, there is no adverse effect. Because these phages are in the mucus they can act as a line of defense before the pathogens can cause an infection. This is similar to what the innate immune system do. In addition to that, bacteriophages are specific and they will bind to their specific pathogen and destroy it. Also, since these phages can be maintain in the mucus, they will only replicated when a targeted pathogen is present and can also provide a somewhat long-term defense against the pathogen. This is definitely a new and exciting way to prevent and suppress infection other than medications.
Yes aren’t phages amazing? I remember when I first learned about them Microbiology learning all the amazing facts about them. I think its interesting that bacteriophages doesn’t stimulate an defensive immune response and are incorporated into our innate immune system.
Can there be damage of the innate immunity or the adaptive immunity by phages in the mucosal surfaces?
When thinking about viruses all that comes in mind is viruses cause diseases. To make matters worse they are not considered alive and not self-replicating. The article blow my mind away by informing not only me but the rest of the world that there is viruses that are good. the good viruses are called bacteriophages or phages. Phages live in symbiotic relationship with animals in the mucosal surfaces. Phages trap bacteria in the mucosal surfaces where they replicate in them and kill them.
The only concern that I have is human immune system needs to fight bacteria by themselves and not using phages. The bacteria can become resistant to phages and the resistance cause more deadly diseases to humans.
I agree, it is probably not a new thing to our body that there are bacteriophages living in our mucus and it was probably one of the reason why humans were able to overcome certain illness because of it. With that being said, bacteriophages can actually induce or enhance our immune system which may lead to a full on immune response. Our immune system is there to help ward off pathogens in our body, however the process is slow. The innate immune system can only do so much while they wait for the adaptive immune system to become activated and are traveling towards the infected area. Bacteriophages could be just as important as our innate immune system by acting as our first line of defense in the mucus, which will definitely slow down the pathogens and allow our immune system more time to progress.
I agree with the phages acting a first line of defense. The phages reduce the amount of pathogens so the innate immunity is busying other foreign material that the phages could not kill
It is also true that bacteria may become resistant to the bacteriophages. But what’s so fascinating is that bacteriophages has to adapt to the situation. Bacteriophages need bacteria in order to replicate itself. With that being said, if the bacteria changes ever so slightly, I believe the bacteriophage will also change in order to be able to continue replicating in the bacteria. This make the bacteriophage a component that will continuously fight off the bacteria for our body. Since it is a bacteriophage, its target is always a bacteria, which means, our human cells will never be harmed by them.
I am too excited to see that research has advanced to a point where science is now finding ways to eliminate infection using a more natural approach. What confuses me slightly about this form of treatment is the concept of specificity. As touched on above, phages would be used to target a specific virus like the example in the article of T4 and E.Coli. This discovery is truly amazing because it validates the overall topic of phage therapy being beneficial. Although we can see that it could eventually be an option for viral treatment, what about the long run. Also mentioned above, this type of therapy would be useful for the innate immune response, but what about subsequent exposure? Would patients need to have repeated phage therapy for the same virus or would the initial treatment be enough for immunoligical memory?
Furthermore, what about diseases where mucus production and accumulation is harmful? Seeing that mucus would house the phages during this treatment, what about Cystic Fibrosis for example where mucus accumulation can be deadly? Would these patients be able to have this type of treatment say for Influenza that could also be potentially fatal with their disease?
I am all for continuing this research and advancement of phage therapies but I would like to see more specifics about which pathogens this would be effective treatment for as well as if there are limitations for immunocompromized individuals.
Previous knowledge has proven that mucus is probably one of the main entries for viruses. The fact that phages have the ability to increase amongst the presence of bacterial targets to help treat our body is something we should not take for granted. An experiment justified the abundance of phages is mucus dependent and prevents the epithelium from infection. Mucosal bacteria becomes limited because the phage is able to maintain interaction with the bacterial host. The symbiotic relationship is so important because our bodies would be more vulnerable to obtaining viral or bacterial infections.