Researchers have found that tuberculosis (TB), which is most commonly found in the lungs and other parts of the body, can spread to the bones.
Spinal damage caused by TB was previously a problem IdentifiedIn 9,000-year-old Egyptian Mummies. Only about 6,000 people live in Egypt today. 2 percentApproximately 65% of TB cases in the US are due to skeletal TB. Pott’s Disease.
Strangely, however, something happened during a TB epidemic in North Carolina in the mid 2000s. The epicenter of the outbreak was a person who apparently contracted TB from Vietnam.
In a work environment, the disease was transmitted to others. Fourteen of six people with TB had reached their bones, and four of them had pulmonary disease.
“That’s way higher than 2 percent.” SaysJason Stout, infectious diseases physician at Duke University.
The chances of this happening randomly were astronomical (approximately 5×10-6).
“I’m an epidemiologist. Clinical trialSpecialist and I was left scratching our heads,” Stout Says.
Stout kept this puzzle in his mind for many years. Then, David Tobin, Duke University molecular geneist, spotted an opportunity.
Tobin offered to look at samples taken from infected people during this unusual TB outbreak.
We know that the bacteria responsible for TB is known asMycobacterium tuberculosis)Moves around the body Invading macrophages – immune cells that swallow pathogens. Tobin and Stout sought to determine what makes certain types TB more mobile within the human body.
In a paper published CellThe researchers compared the genetic sequences of the TB strain that caused the North Carolina epidemic with 225 other strains.
They discovered that the outbreak was caused a lineage 1 strain of TB, which was the earliest form of TB to appear.
The lineage 1 strain of the virus is still a major cause of death in the world today, but it is geographically limited to the Indian Ocean.
Specifically, the researchers found that a particular gene that codes for a protein – the EsxM variant – was present in full in the North Carolina TB outbreak strain, but truncated in the ‘modern’ TB strains (Lineage 2, 3, and 4).
An earlier study in the UK that included over 1,600 participants found that lineage 1TB was associated to higher rates of skeletal tuberculosis than lineage 2.
Researchers infected zebrafish using the North Carolina TB outbreak strain to verify that the EsxM variant was required and sufficient to cause TB infection to make TB-infected cells travel further.
They then infected a different group of zebrafish using a TB strain with a mutant EsxM variation. A mutant TB strain caused a two-fold decrease in travel distances for macrophages than the full-length EsxM version.
Researchers also found that macrophages with the mobility genes were faster in moving to the site for a tail fin injury than those without it.
Researchers also sequenced 3,236 strains to find the EsxM gene in all modern strains. This suggests that the mutation may have an evolutionary advantage.
The team believes that the mutation has restricted TB’s spread within the body. However, it has also allowed TB strains of’modern’ to spread more widely through staying in the lungs. This allows them to disperse more easily via infected patients’ breathing.
This paper was published by Cell.
