Endophytes

 

by John Aitken

A few years ago, I was part of a small team looking at indigenous “cures” for medical complaints. The original settlers in New Zealand were the Maori. Prior to the arrival of the Europeans, Maori had developed an extensive knowledge of the healing powers of local plants. Then the Trojan Horse, in the form of unwanted invaders arrived, and the indigenous Maori had to either cooperate or perish. In fact, they adapted to the colonisation with many trials and against great odds, and are now respected and admired in my country as equal partners in the journey.

In the Nineteenth century, researchers gathered oral histories from Maori, including the therapeutic use of plant compounds. These records became invaluable to later researchers, and revealed that some of these medicines contained active compounds able to provide relief for ongoing health problems. As a microbiologist, I was interested in the small amount of work done on the use of ointments to relieve infections.

I had always been keen to try some bioprospecting, so early one morning we shouldered our packs and wandered up to the National Parks to collect specimens – funded by a small amount of money from the government.

Until those trips, my knowledge of bacteriology was limited to human microbiology. In the course of our work on the plants we collected, I learned that there was no such thing as a plant that was sterile (i.e. did not contain bacteria or viruses.) All plants carry passengers in the form of microbes. These passengers are called endophytes.

In the USA, this apparently harmless ability became a sinister threat. The 2012 outbreak of E. coli O157 foodborne illness provided convincing evidence of the existence of endophytes within the leaves of lettuce plants. The E. coli O157 had entered into the lettuce leaves and was able to withstand the cleansing agents applied to the outside of the infected leaves.

In the plant world, endophytes exist within plants to perform essential functions in the plant – stimulation of plant immunity, competitive inhibition (making sure there is no room left for an invader) and production of chemicals capable of killing other bacteria (antibiotics). This is a process called “symbiosis.” Symbiosis occurs when two organisms co-exist and one, or both, organisms benefit from the relationship. In plants, endophytes have evolved to be part of the growth mechanisms of the plant. They are found in the roots and in the leaves.

Sometimes endophytes may threaten the plant host. In droughts, for example, endophytes may compete for moisture and nutrients, or they may assist the plant to survive. In New Zealand, we see this happening in real-time. A plant endophyte, Pseudomonas syringae actinidiae (Psa V), evolved to become a particularly efficient pathogen in kiwifruit plants. The Psa V organism quickly killed the kiwifruit plant by over-running the natural defences of the plant and blocking all the passageways that carried water and nutrients. The plants quickly wilted and died in the thousands. The Psa V has since evolved to become resistant to the main treatments used on the plants by the orchardists.

Psa V is an example of overstepping of boundaries between bacteria and plants in the Plant Kingdom. This method of attack can be easily demonstrated in a laboratory, and has been extensively researched by horticultural scientists. The introduction of bacteria into the plant stimulates the immune system and is necessary for plant survival, but sometimes the organism becomes an invader, turning the immune system against itself with lethal consequences.

Of course, this would never happen in us. Our blood is sterile, and is uncontaminated by microorganisms. But is that true? Is there the equivalent of a Berlin Wall between us and the bacteria that live with us and surround us? There is no evidence of such an impenetrable wall existing. The term “leaky gut” admits the possibility that there is continual microscopic spillover into the bloodstream. It is just that the defences in the bloodstream, such as white cells and antibodies, can quickly get on top of the occasional interloper.

But there is also mounting evidence that human blood is not sterile. Virologists regularly find viruses circulating in the blood. Some viruses will exist in the bloodstream for the entire lifetime of the host. (Epstein-Barr virus, for example.)

This then raises questions of interest to us all:

• If Crohn’s disease is triggered by mycobacteria, then do the Mycobacterium species exist in the blood for the long term?
• Is Crohn’s disease the human equivalent of a plant disease? Is Crohn’s disease like Psa V in kiwifruit?
• Are there naturally occurring mycobacteria being carried around the bloodstream, stimulating the immune system, and are these helpful buddies of ours elbowed out by the superior pathogenic powers of the new mycobacterial invader?

That theory (and it is just a thought, really) would be more readily accepted if it could be demonstrated that human blood was not sterile, but contained extremely hard-to-detect microorganisms resident in the bloodstream of the normal human (if there is such a thing!) which is able to survive undetected while stimulating immunity.

In fact, we already know that this state exists. Bacille calmette-guerin (BCG) is a living vaccine prepared from the cattle stain of Tuberculosis, Mycobacterium bovis. After inoculation into the patient, BCG exists in the body for decades, adopting a “stealth” form. Researchers have isolated living BCG vaccine from patients years after they were vaccinated. In these patients the BCG form is difficult to detect, and even more difficult to culture; nevertheless, it is there, stimulating the immune system.

What has this to do with Crohn’s disease? The answer to that is still up in the air. What the BCG story demonstrates, however, is that there is an underlying mechanism capable of retaining mycobacteria in the body for decades, living and presumably stimulating the immune system.

Out of all of these thoughts come several questions we desperately need to answer:

• Is this process both the Trojan horse hiding the enemy, and our Achilles heel?
• Are we unwittingly entertaining invaders in the guise of good mates?
• Is this how Crohn’s disease is precipitated in the patient?