On the Curious Motions of Syphilis and Lyme Disease Bacteria
The bacteria that cause syphilis and Lyme Disease have something extraordinary in common: they manage to propel themselves through their environment in spite of the fact their tails are located inside their bodies.
The bacteria that cause syphilis and Lyme Disease have something extraordinary in common: they manage to propel themselves through their environment in spite of the fact their tails are located inside their bodies.
For bacteria, they're also unusually shaped and active. In this movie, you can see the bacteria that cause Lyme Disease moving like living, squirming cavatappi.
Syphilis and Lyme Disease -- which together have two of my very favorite Latin names -- Treponema pallidum and Borrelia burgdorferi -- belong to a group of bacteria called spirochetes that look like squiggles and move like corkscrews. Spirochetes don't just inflict misery on humans and other animals, though. Many of them do just fine on their own in rivers, ponds, lakes, and oceans. Here's one captured from a salt marsh in San Francisco Bay.
Today, we know that only some of them are actually helical like corkscrews, while others like T. pallidum and B. burgdorferi are flat waves like sines and cosines. In this slow-mo video of a tethered B. burgdorferi (the scientists somehow pinned it down) you can see how the bacterial profile briefly flattens as it turns. The first part of the video is in real time. The second slows the action down. Watch the third rotation in particular very carefully.
So how do bacteria that appear so athletic manage their acrobatics with tails planted quite firmly (and seemingly uselessly) inside their bodies?
Whatever their shape, all spirochetes have tails, or flagella, of the same type that other bacteria have: a long helix joined by an L-shaped connecter called a hook to a motor embedded in the cell's membrane. In most bacteria, these tails protrude from the back of their owners into the environment. They are rigid and rotate, powered by the motors at their base. These flagella function much like a corkscrew called a Screwpull -- their rotation generates thrust. In the case of the screwpull, the torque is used to extract a cork from a bottle.
In the case of bacteria, the torque pushes the bacteria forward or pull it backward, like the screws on a submarine or ship.
The many tails of spirochetes -- they usually have several -- are embedded in rows near each end of the organism and coil back around the body, terminating somewhere near the middle. Stripped of their flagella, these bacteria revert to straight rods, so the rigid tails must act like skeletons that bend the bacteria into their characteristic shapes. In this schematic of a flat-wave spirochete, the purple flagella are clustered together into band-like ribbons:
Fig. 1 from Harman et al, 2013. Click image for source.
The ribbons overlap somehow in mid-section of B. burgdorferi. It isn't clear yet whether the two ribbons form a continuous band or whether the ribbons terminate on opposite sides of the cell. This whole bundle is wrapped inside a protective outer membrane (the outer membrane has been omitted in the image above). It fits tightly around the spirochete -- so tight, in fact, that under high magnification it's possible to see that the outer membrane bulges where the flagella pass underneath, a bit like bacterial skinny jeans.
So how do this all this machinery push spirochetes forward? When the two ribbons of flagella turn in opposite directions (one end clockwise, the other end counterclockwise), the spirochete moves in a straight line. Since they are attached at opposite ends, they must rotate in opposite directions for a wave to propagate in the same direction down the length of the cell. In effect, they turn their entire body into one giant flagellum. In this illustration of how it might work, the spirochete slithers by like a sea serpent.
When the flagella spin in the same direction (i.e. both clockwise or both counter-clockwise), the spirochete flexes or bends irregularly, as you saw in the first film of this blog post.
There is fluid -- perhaps like transmission or brake fluid -- in the space between the cell body and the outer membrane in which the bands of flagella lie, and this fluid is vital to movement. It acts as lubricant and a purveyor of the forces acting on the outside of the cell, and without it, the flagella would tangle. Resistance from thick fluids or barriers outside the cell bearing down on the outer membrane are transmitted via the outer membrane and this fluid to the internal flagella, whose slow-down is in turn relayed to their motors, which bog down in response. In this way, the internal propulsion system of a spirochete senses and responds to the outside world.
When the viscosity, or thickness, of the fluid the bacterium is swimming in goes up, B. burgdorferi slows down. That's what you'd expect. But when scientists added chemicals that increase both the viscosity *and* elasticity of the bacterial environment, B. burgdorferi actually sped up. This counter-intuitive result makes more sense when you realize that our flesh is largely a mesh of collagen fibers that responds to bacteria with both elastic and viscous forces. B. burgdorferi bacteria are even able to squeeze through gelatin with pores significantly smaller than their own bodies.
Together, these results suggest that these bacteria may owe their success as pathogens to their ability to worm their way into the tight places of our bodies in a way externally flagellated bacteria cannot. Inside us, they can drive pretty much wherever they want.
Recently, scientists at the Universities of Arizona and Connecticut wanted to know more about the dynamics of B. burgdorferi motors, and whether Lyme Disease bacteria can serve as a good model for T. pallidum. Biologists have never managed to culture syphilis outside the human body, greatly hindering our ability to study it. Based on their models of the motions and physics of these bacteria, published in November inBiophysical Journal, they believe that B. burgdorferi is a reasonably good stand-in for studying T. pallidum movement, with the exception that B. burgdorferi can swim through thicker, more viscous fluids. That's probably because it has more flagella than T. pallidum, and hence, more horsepower.
In this movie, you can compare the motions of the two bacteria for yourself:
The remarkable engineering of these bacteria are probably a major reason spirochetes have been such successful pathogens in humans and other animals. Syphilis and Lyme Disease are better at penetrating our bodies than almost any other organisms. Spirochetes cross barriers that are impenetrable to almost anything else, including basement membranes and the linings of organs like intestines called endothelium that function to keep the kajillions of bacteria in your gut out of the rest of your body. In humans, syphilis and Lyme Disease bacteria easily penetrate the normally sacrosanct blood-brain barrier to infect the central nervous system. Syphilis can invade the placenta and infect an unborn child.
This extraordinary ability is reflected in the symptoms of these brutal diseases. The characteristic bullseye rash of Lyme disease seems to be the result of their penetrative ability, as the spirochetes burrow into the skin and soft tissue of their new host and trigger a destructive inflammatory response radiating from the bite that delivered them. Lyme Disease and syphilis sufferers -- the latter of which have been legion among the great and small in human history, including many people today -- may experience damage to multiple organs, joints, and the brain and nervous system as a result of the same damaging inflammation. In syphilis, the spirochetes seem to be amazingly good and fast at this, managing to find their way into blood, lymph nodes, bone marrow, spleen, and testes in laboratory animals in less than 48 hours. For an organism just a dozen or so micrometers long, which must penetrate countless tough membranes evolved to keep them out with no obvious means of propulsion -- which can, in fact, move only by engaging its whole body in a beautiful but lethal shimmy -- two days from tick to testis ain't bad.
Reference
Harman M., Vig D., Radolf J. & Wolgemuth C. (2013). Viscous Dynamics of Lyme Disease and Syphilis Spirochetes Reveal Flagellar Torque and Drag, Biophysical Journal, 105 (10) 2273-2280. DOI: 10.1016/j.bpj.2013.10.004
Charon N.W., Cockburn A., Li C., Liu J., Miller K.A., Miller M.R., Motaleb M.A. & Wolgemuth C.W. (2012). The Unique Paradigm of Spirochete Motility and Chemotaxis, Annual Review of Microbiology, 66 (1) 349-370. DOI: 10.1146/annurev-micro-092611-150145
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