Motile Menace

by Tom Grier

 

Ever wonder how the Lyme spirochete gets around in the human body? This is the question that Dr. Mark Klempner, M.D. asked himself, and was able to help elucidate at the 1996 LDF Conference in Boston. The Lyme bacteria has been isolated from nearly every organ, and every tissue in the human body. Although its numbers are few, what it lacks in legions it makes up for in stealth and persistence.

Several animal studies have shown that in less than a week after being bitten by an infected tick, the host animal can already have the Lyme spirochete deeply embedded inside tendons, muscle, the heart, and even the brain. How is this pathogen able to move about so aptly within the human body? After all, to get from the site of a bite to all these sites, the bacteria must travel through blood vessel walls, extra-cellular matrix, through connective tissue, and then back through blood vessels, and finally into the target tissue itself. Even the characteristic bulls-eye rash itself is a mystery. The bacteria can be found near the outside leading edge of the expanding red rash, far from the original entry site. This means the bacteria must be swimming through skin at the rate of several inches in a matter of a few days. Quite a feat for something only 35 microns long (less than the width of a human hair)!

Dr. Mark Klempner wondered if the bacteria contained any special enzymes that would dissolve proteins, fats, and collagen. Using sophisticated biochemical techniques, it was eventually decided that Borrelia burgdorferi had no special enzymes capable of penetrating these tissues. How then does this bacteria move about?

First of all, the Lyme spirochete is a long snake like organism that has an internal bundle of flagella that contracts like a large muscle. The contraction of the flagella causes the spirochete to twist itself and propel itself forward. The internal arrangement of the flagella actually allows it to swim faster in thicker fluids because it has something solid to push against. Just like a jumper could jump farther off of hard ground than soft mud, the spirochete swims better in tissue than blood. The pointed ends allow the bacteria to fit in between crevices and work its way through cracks.

Second, the Lyme spirochete always seems to bind to tissue tips first. This suggests some kind of receptor site. Dr. Klempner soon discovered that in addition to the tips of the bacteria binding to the different tissues, the tips were also binding a blood borne enzyme called plasminogen. When activated, plasminogen is an enzyme which initiates several reactions to occur. It is chemotactic, meaning it helps begin the process of attracting inflammatory cells to the site of tissue damage. It helps initiate a cascade of other enzymatic reactions, such as fibrinogen conversion to scar tissue, the release of elastase to dissolve tendon, collegenase to dissolve connective tissue, and basement membrane laminase to dissolve cell membranes. It helps cause the release of vasoactive substances, which cause blood vessels to become weakened and leaky. In essence, by binding plasminogen to the tip of the bacteria and then the bacteria ramming this enzyme into the confines of the blood vessel walls, it causes our own cells release the enzymes necessary to dissolve our own cells!

When you think of it, this is a very economic way to travel. Why pack away several extra genes and the machinery to make catabolic enzymes when the bacteria can just induce our own bodies to do the work for us! This is an advantageous piece of evolution for the pathogen, because it has learned to use our own enzymes against us to ensure its own survival. Once the bacteria escapes the blood stream where our immune system is strong, it soon finds safe haven between the fibers of a tendon, or in the immune sequestered brain where white blood cells are forbidden to enter.

Amazingly, it would seem that Borrelia burgdorferi has evolved ways in which to penetrate virtually any tissue of the human body simply using our own enzymes to break down the cellular glue holding us together. Yet an even more amazing feat may be how the bacteria eludes our immune system long enough to establish itself throughout the human body.

Dr. David Dorward from the NIH Rocky Mountain Laboratories, showed that when healthy normal human B-cells were placed in a culture with live Borrelia burgdorferi, that it was only a matter of moments before the spirochetes started to attach and penetrate the anti-body producing white blood cells. Once inside the cell, the bacteria should be killed by a process wherein the B-cells lysosomal enzymes dissolve the bacteria, but this does not happen. Instead the bacteria actually thrive, and eventually destroy the lymphocyte.

What is much more disconcerting is that using a time lapse video camera, the spirochete can be seen to enter the B-cell and exit a short distance later, but when it exits it appears to be wearing the membrane of the B-cell. The live motile bacteria then swims about unharmed in the sea of B-cells, because by wearing the cloak of its enemy it goes undetected. This stealth type camouflage will prevent antibodies from attaching to it; it prevents the compliment enzymes in the blood from finding and destroying it; and it eludes the scavenger white blood cells, such as macrophages and killer T-cells, that normally hunt down and destroy foreign pathogens. What this means is the bacteria seems to have evolved a sophisticated defense mechanism to avoid our immune system.

In summary, we have a highly evolved bacteria that is highly motile, can dissolve any tissue it desires so it can find immune privileged sites, and can camouflage itself from our own immune system by wearing the membrane of the very cells that are supposed to track it down and kill it. You have heard of the wolf in sheep's clothing? Apparently in the microscopic world of predator and prey the same tricks apply!