Syphilis constantly changes its genes to infect humans several times

The syphilis-causing bacterium, Treponema pallidum (Treponema pallidum), probably uses a single gene to elicit an immune response, according to UW Medicine in Seattle. By shuffling DNA in a single gene, syphilis remains one step ahead of the immune system to counter eradication (annihilation). An article about this is published in Plos journal.

This finding can help explain how syphilis can lurk in the body for decades, thereby nullifying the immune system’s attempts to eradicate it. It may also explain the ability of the bacteria to re-infect people who were previously infected and needed to gain some immunity to the disease.

Although syphilis is still easily treated with penicillin, the incidence rate in the United States has steadily increased over the past two decades. In 2018, the number of infections in the United States exceeded 115,000. Worldwide, there are about 6 million new cases of syphilis among adults. Infection causes about 300,000 fetal and newborn deaths each year. However, despite its importance as a cause of the disease, relatively little is known about the biology of Treponema pallidum.

One of the reasons is that until recently it was impossible to grow it in laboratory conditions. As a result, many of the laboratory tools used to study other bacteria have not been specifically designed for syphilis.

In a new study, scientists compared the genomes of syphilis bacteria collected from a person who was infected four times. He ended up at UW Medicine, a study of cerebrospinal fluid abnormalities in individuals with syphilis, conducted by Dr. Christina Marra, a professor of neurology. Samples were taken from his blood during two infections that occurred at intervals of six years. Between these infections, he was infected and treated two more times.

The researchers wanted to find out if there are differences between the genomes of bacteria from the first and last infection. These differences can show how bacterial genes have changed and how these changes could allow bacteria to infect a person whose immune system has already been seen, and to develop an immune response to several different strains of syphilis. Surprisingly, the researchers found that there were very few changes between the genomes of two different samples, with the exception of one gene.

“For about 1.1 million bases that make up the bacterial genome, there were about 20 changes. This is very small. But in this one gene we saw hundreds of changes”.

Dr. Alex Greninger, associate professor of laboratory medicine at the UW School of Medicine.

This gene, called the Treponema pallidum K (tprK) repetition gene, provides instructions for the synthesis of a protein found on the surface of a bacterium. Proteins on the surface of bacteria are usually more easily detected by immune cells and therefore are often the main targets of an immune attack.

Researchers first showed that TprK generates significant diversity in seven distinct regions in which DNA sequences from other parts of the bacterial genome can be reversed. This process is called gene transformation. Work in their laboratory has shown that bacterial cells with new tprK variants can evade the immune response, causing a persistent infection that can lead to late stages of syphilis.

This bacterium has a “deck of cards” in its genome, from which it can take and play these variable regions, essentially changing the proteins on “its own hand”. These substitutions alter the appearance of the protein on the surface, which allows it to elude the immune system.

“There are many other bacterial genomes, and they are much more interesting than the treponema gene, with the exception of this one gene. It can generate an amazing amount of diverse sequences in these variable regions without compromising the ability of the protein to function”.

Amin Addetia, one of the authors of the study.

Although bacteria, viruses, and parasites can have many proteins on their surfaces that the immune system could detect and attack, in many cases only one protein seems to attract most of the attention. Such proteins are called immunodominant.

According to Groeninger, they can protect the bacteria by attracting the attention of the immune system. A protein acts as a distraction that distracts the immune system from proteins, which can be the Achilles heel of the bacteria. More work will be needed to determine if this is the case with TprK.

The findings may help researchers develop vaccines that will allow the immune system to either attack TprK more efficiently or ignore TprK and target other, less variable syphilis proteins.

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