Can a bacteriophage infect a human cell?

Can a bacteriophage infect a human cell?

It's a very interesting question that has been making scientists to scratch their heads over the possibility of these "minute guys" (phages) if they can cause any undesirable effect to our bodies. This same question would have been asked by one who wants to know if phages are safe for humans especially when they are used as an alternative to treatment. Worries about their safety when used live (without being attenuated) never left the heads of authorities who are responsible for approving drugs for human/animal use.  This has been a nightmare for phage-based pharma companies for so long although authorities are currently opening up for many phage products to hit the market.

Humans contain lots of bacteria in our microbiomes, mostly in the gut. These bacteria can be attacked by bacterial viruses called bacteriophages. Photo by Frontiers

Bacteriophages, viruses that infect bacteria, have re-emerged as powerful regulators of bacterial populations in natural ecosystems. Phages invade the human body, just as they do other natural environments, to such an extent that they are the most numerous group in the human virome. This was only revealed in recent metagenomic studies, despite the fact that the presence of phages in the human body was reported decades ago. The influence of the presence of phages in humans has yet to be evaluated; but as in marine environments, a clear role in the regulation of bacterial populations could be envisaged, which might have an impact on human health. Moreover, phages are excellent vehicles of genetic transfer, and they contribute to the evolution of bacterial cells in the human body by spreading and acquiring DNA horizontally. The abundance of phages in the human body does not pass unnoticed and the immune system reacts to them, although it is not clear to what extent. Finally, the presence of phages in human samples, which most of the time is not considered, can influence and bias microbiological and molecular results; and, in view of the evidence, some studies suggest that more attention needs to be paid to their interference.

What type of bacteria do bacteriophages infect?

Despite the specificity of bacteriophages on infecting a certain species of host bacteria, there are no known bacteria that have got no phages to infect them. Bacteria do evolve to resist attacks while bacteriophages as living entities evolve with new strategies to initiate an attack.

Is there a possibility of a bacteriophage infecting human cells?

Bacteriophages do not infect human cells, therefore they can not cause disease to humans. They only infect the bacteria they are specific to. Once they have destroyed all of the bacteria they have infected, your immune system efficiently removes the bacteriophages from your system. Bacteriophages are self-limiting and harmless to humans although indirect they may cause undesired activities like transferring antibiotic resistance genes (ARGs) from one bacteria to another which is mostly caused by lysogenic phages.

What is the role of bacteriophages and the human microbiome?

The bacteriophage (“phage”) is a virus known as a bacteria eater; however, a more appropriate term would be natural bacteria predator. Phages are found in all microbial environments. The battle between phages and bacteria dates back to the beginning of life formation. Bacteriophages are very selective towards the bacteria they target. This selectiveness allows phages to eliminate a specific type of harmful bacteria, whilst leaving all the other bacteria untouched, with no known side effects to the human body.

Phages compose the majority of the viral population in the human gut microbiome. The most common order of bacteriophages found in the gut microbiota belongs to the order of Caudovirales. The order consists of three families of lytic viruses that target specific types of bacteria and archaea; Myoviridae (long contractile tails), Siphoviridae (long noncontractile tails), and Podoviridae (short non-contractile tails).

In the last decade, the viral portion of the gut microbiota has received a lot of attention. Bacteriophages used in supplements in the US; LH01-Myoviridae, LL5-Siphorviridae, T4D-Myoviridae, and LL12-Myoviridae were chosen particularly to target pathogenic strains of Escherichia coli. The selective nature of phage preference towards the targeting of bacteria allows a non-invasive approach to therapy. Scientists can filter out bacteriophages that would be effective against pathogenic bacteria and the treatment would be completely harmless to the human body and to the present beneficial bacteria.

Immune system, gut microbiome, and phages

It is in the microbiome that our body’s immunity is built, which makes maintaining its health that much more of a priority. It is often referred to as the barrier organ; playing a crucial role in protecting the rest of the body from invading microbes. The development of the gut microbiota and our immune system begins at the fetal stage. Studies show that infant microbiomes contain a diversity of beneficial bacteria, as well as some bacteria that are received from the mother’s milk. Over the years, adults tend to lose some of the bacteria, and whilst some can be replaced, others cannot. These bacteria play a very important role in maintaining a balanced environment within the body, including a healthy immune system and metabolism.

Research surrounding the effects of bacteriophages on the human immune system is also on the rise. Whilst some studies show phages can affect the immune system negatively, others show promising results in bacteriophages strengthening the system. It is important to note, bacteriophages are not all categorized under one label. The difference between virulent and temperate phages is a huge factor to consider as it directly reflects on whether bacteriophages work towards the wellbeing of the immune system, or can cause damage.

By nature, temperate phages or bacteriophages that use lysogeny, use the bacterium as a host organism and have their unique symbiotic relationship with it. They will do whatever it takes to keep their host safe and protected from invasion and ultimately death. Some studies show that this defensive mechanism can also include assistance toward the biofilm formation in bacteria. It is only when the prophage (embedded phage in the bacterium’s DNA), finds that all hope is lost for the survival of the host, that it has the ability to switch to the lytic cycle, bursting out of the bacterium in order to survive.

Lytic bacteriophages or virulent phages are those that utilize the lysis of the bacterium and are used in phage therapy. Their mechanism is more straightforward; they target the bacterium, insert their genetic material and rapidly begin to multiply within the bacterium, ultimately killing the host by bursting out of the organism and releasing the newly formed phages. Positive immunomodulating effects were seen in studies that used lytic phages for the treatment of bacterial infections such as the use of Escherichia virus T4; a phage from the subfamily of Tevenvirinae from the family of Myovirinae.

Probiotics, prebiotic & bacteriophages

Today, probiotics are known by many as supplements that carry beneficial bacteria to our microbiome. These bacteria become part of the gut ecosystem and join the symbiotic relationship of our gut microbiota; given the environment to survive in, and in return contribute to our overall health. One of the biggest concerns about probiotics is the quantity found in supplements. For a long time, it was considered that the larger the number of bacteria found in a probiotic supplement, the greater the chance these bacteria will have to survive the journey to the gut microbiome and thrive in their new environment. However, the quantity alone may not be as important as the nutritional conditions to allow that bacteria to flourish once the gut is reached. This is where the addition of prebiotics becomes crucial.

Prebiotics, a relatively new supplement in the market, are recognized for their importance to the sustainability and growth of beneficial bacteria in the microbiome. Prebiotics are the nutritional elements that probiotics feed on and many are found in fermented foods. Combined intake of prebiotics, together with probiotics, maximizes the chances for the beneficial bacteria to thrive in the microbiome. In order for the beneficial bacteria to continue to multiply and remain in the gut, they need nutrients that allow them to develop. Prebiotics fulfill that nutritional need which results in stable and healthy gut microbiota.

The unique nature of bacteriophages allows for a treatment that is specific, non-invasive and contributes to the overall health of the gut microbiota and the immune system. Lytic phages can be carefully selected from phage libraries, for the targeting of resistant bacteria commonly known to invade and disturb the human gut microbiota; whilst leaving all the other bacteria untouched, with no known side effects to the body. Bacteriophages can further contribute to helping restore balance to the human gut microbiome caused by the pathogenic microbe.
Some complex supplements
such as Terraflora Advanced Care prepared by enviromedica (The phage has no association or affiliation with enviromedica) are already available on market and claimed to provide a triple approach towards stabilizing and maintaining a healthy gut microbiome. Carefully selected bacteriophages target harmful gut bacteria, while beneficial bacteria in the probiotics are introduced into the gut microbiota and prebiotics ensure the beneficial bacteria have enough nutrition to keep them alive and thriving in a healthy gut microbiome.

Phages are really very beautiful and the way they reproduce is quite interesting. A phage attaches to a bacterium and injects its DNA into the bacterial cell. The bacterium then turns into a phage factory, producing as many as 100 new phages before it bursts, releasing the phages to attack more bacteria. This means that phages can grow much more quickly than bacteria. In some countries, particularly in Eastern Europe, phages are actually used to treat bacterial infections. Each phage can only kill one type of bacteria, so if a doctor knows what kind of bacteria is infecting a patient, it might be possible to give the patient a phage that can infect and kill that type of bacteria. Phages cannot infect human cells, and so they pose no threat to us.

References and credit:

Frontiers for Kids

Laboratory Insider


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