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Treponema pallidum. (Dr. David Cox/CDC)

Changing a Single Gene Lets Syphilis Lurk Hidden in The Body For Years

30 APRIL 2020

Thanks to the advent of antibiotics, syphilis is not the same deadly threat it was centuries ago, but it's still a common sexually transmitted infection worldwide, and one that can be very dangerous if not treated.

 

Estimates put new infections worldwide at about 6 million cases annually, with the disease causing over 100,000 deaths among adults each year, although the toll of foetal and neonatal cases, exposed while in the womb, is much higher, with an estimated 300,000 deaths annually.

Despite this ongoing global burden, the spiral-shaped bacterium that causes syphilis – Treponema pallidum subspecies pallidum (hereafter T. pallidum) – remains much of a scientific mystery.

009 treponema pallidum 1Treponema pallidum. (Dr. David Cox/CDC)

This helically coiled pathogen is a particularly evasive organism, both in the context of infections – where it can elude the immune system (lasting decades within the body in some cases) – and in our ability to study it. Scientists only recently learned how to culture the entity, after a long century of trying.

In the first context, T. pallidum's formidable abilities as a 'stealth pathogen' have been attributed to the protein-sewn cloak of its bacterial surface, which seems to hide it from immune system detection.

"Key to the capacity of the syphilis spirochete for immune evasion and thus 'stealth pathogenicity' is its unusual outer membrane," one group of researchers observed in 2016.

 

Now, a new investigation might be able to explain just how this stealth mechanism succeeds so effectively.

Scientists from the University of Washington compared the genome sequences of T. pallidum strains taken from a man who was diagnosed with syphilis four separate times over the course of six years.

Comparing the strains responsible for the first and last infections, the researchers wanted to see how changes in the bacterial genes might have augmented T. pallidum's ability to reinfect this poor patient.

While they did identify differences between the two genomes, the genetic sequences were mostly identical, reflecting a "paucity of coding changes across the genome" outside of one particular gene.

That gene, called Treponema pallidum repeat gene K (tprK), encodes one of the bacterium's surface proteins, known as TprK, and it was vastly different between the two genomes.

"Across the about 1.1 million bases that make up the bacteria's genome there were about 20 changes total. That's very low," says lead researcher and clinical pathologist Alex Greninger.

"But on this one gene, we saw hundreds of changes."

 

The researchers speculate that the resulting mutations in TprK surface proteins due to the new tprK genes could represent a "genetic basis through which T. pallidum escapes cross-protective immunity", enabling the bacterium to effectively don a disguise, by altering the arrangement of its outer membrane.

The team acknowledges their findings require further replication. For starters, we're only looking at a sample size of one patient here, and the researchers also acknowledge the limitations inherent in the new techniques used to culture T. pallidum, which depends on rabbit models.

Nonetheless, it certainly looks like they've uncovered something strange going on here.

"I've looked at a lot of bacterial genomes, and they're a lot more interesting than the Treponema's, except for this one gene," explains research scientist Amin Addetia.

"It can generate an astounding number of diverse sequences within these variable regions without impairing the protein's ability to function."

The findings are reported in PLOS Neglected Tropical Diseases.