Treponema pallidum (Syphilis)

Treponema pallidum can be considered a gram-negative bacterium even though its cell envelope differs from other gram-negative bacteria.

You might know T. pallidum because it causes syphilis, a sexually transmitted disease that affects the skin and mucous membranes of the external genitalia, and also sometimes the mouth.

Treponema pallidum is an obligate parasite bacteria, meaning it can't survive outside a living body. To be more specific, outside of a human being's body. They belong to a group of bacteria called spirochetes, which are long and thin, and contain endoflagella, which are a band of protein filaments that coil within the spirochetes, and give them a spiral shape - kind of like a curly fry, but a little less appetizing. The endoflagella also help the spirochetes to move around by spinning or twisting, a bit like a drill that’s slowly boring into a piece of wood.

People that have syphilis can transmit the disease to others, in one of two ways. The first way is called acquired syphilis and that’s when Treponema pallidum enters the body through bodily fluids. That can happen when there are tiny cuts, or breaks in the skin or mucous membranes of the external genitalia or mouth and when there’s sexual contact - including oral, anal, and vaginal sex.

It can also happen when people share contaminated needles, or when they have direct contact with a skin lesion on an infected person, because the lesion is covered in this fluid which is rich in spirochetes. The second way is called congenital syphilis and that’s when a pregnant person has syphilis and Treponema pallidum infects a baby either in the uterus or while the baby exits through the vagina at birth.

In acquired syphilis, there are three stages to the infection. The first stage is called primary syphilis or the early localized stage, and it usually starts 1 to 3 weeks after the T. pallidum lands on the skin or mucous membrane.

During this stage, the spirochetes destroy the soft tissue and skin wherever they enter the body, and that results in the formation of ulcers called syphilitic chancres. A syphilitic chancre is painless - and you can remember that by dropping in a “u” to make it chan”cure” like you’re “cured” of the pain. These chancres have a hard base, raised borders, and are usually covered by a fluid rich in spirochetes, and this can spread to other parts of the body as well as to other individuals.

In individuals who acquire syphilis through sexual contact, the primary chancre develops around the external genitalia. However, for individuals that acquire syphilis by physically touching a lesion or in some other way, the primary chancre might appear on the hands or some other part of the body.

Syphilitic chancres typically heal on their own over a few months, but during that time, some spirochetes go to nearby lymph nodes where they cause lymphadenopathy, which is lymph node enlargement, and then they get into the lymph and finally into the bloodstream. If syphilis is acquired through something like a blood transfusion, then there may not be any early localized stage at all and no primary chancre.

The second stage is secondary syphilis, or the dissemination stage, and it occurs about 6 to 12 weeks after the infection. During this stage, spirochetes enter the bloodstream, which is called spirochetemia, and this causes generalized lymphadenopathy, which is when spirochetes can be found in lymph nodes throughout the body.

The spirochetes like to attach to and infect endothelial cells in small capillaries near the skin. This causes a non-itchy maculopapular rash, which are small bumps that are either flat or raised. The rash starts on the trunk and spreads out to the arms and legs and eventually to the palms, soles, genitalia, and other mucous membranes.

These rashes can sometimes be pustular, which means they’re filled with the white fluid pus, or they can be papulosquamous, which is when they’re really scaly and hard. In addition, there can be something called condyloma lata, which are smooth, white, painless, wart-like lesions, and they appear on moist areas like the genitals, around anal region, and the armpits. So these various rashes can erupt all over the body, and the lesions are chock full of spirochetes, making secondary syphilis the most infectious stage. The rashes from secondary syphilis usually resolve within a few weeks to months.

After secondary syphilis is a latent phase called latent syphilis. This is when the disease enters a dormant or asymptomatic phase. During this phase, the spirochetes can mostly be found in the tiny capillaries of various body organs and tissues. Latent syphilis can be further divided into an early phase and a late phase.

Early latent syphilis occurs within a year of infection, and during that time the spirochetes can re-enter the blood - so this means that during early latent syphilis they can still be found circulating in large numbers in the blood, causing symptoms of secondary syphilis. However, the late latent phase is generally after a year, and that’s because the spirochetes generally stay within the tiny capillaries of various body organs and tissues.

As it turns out, only a few spirochetes are actually found in the capillaries of tissues and organs, but there is a severe immune response—so severe that it causes tremendous damage to the cells there. And that triggers the next phase which is tertiary syphilis.

In tertiary syphilis, there’s a type IV hypersensitivity reaction, which means that there’s an immune response that’s mainly led by the T cells and they recruit phagocytes like macrophages, and cause the release of proinflammatory cytokines such as tumor necrosis factor, IL-1, and IL-6.