TB over Time

Tuberculosis, MTB, or TB (short for tubercle bacillus), in the past also called phthisis, phthisis pulmonalis, or consumption, is a widespread, and in many cases fatal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit respiratory fluids through the air.

In the mid 1990s, a surveyor tasked with renovating a Dominican church in the Hungarian town of Vác discovered a crypt hidden beneath a side chapel that contained the remains of some 265 people, from aristocrats to commoners, many of whom had been naturally mummified by the dry air and the wood chip-lined pine coffins that held the bodies.They looked like gold dust and were well preserved. Moreover, many of the remains were found with identifying information, death records, and even reports of symptoms they’d experienced before they’d died, some of which resembled those of TB infection.

Hence group of researchers decided to sample these mummies. In addition to sampling the mummies, X-ray of chest of some  of the centuries-old corpses were done which further revealed that many had calcified lung lesions characteristic of TB infection. Initial PCR-based genetic screens of 168 of the bodies confirmed that TB was rampant,  more than half tested positive for M. tuberculosis DNA .The researchers demonstrated that a straightforward metagenomics approach, with no targeted amplification, was able to generate M. tuberculosis sequences from a lung sample of a Vác female who had died in 1797.

The study was repeated , this time they obtained 14 complete M. tuberculosis genomes, representing 12 distinct genotypes, from eight of the Vác mummies. All the bacterial strains belonged to M. tuberculosis lineage 4. Comparing the sequences to modern M. tuberculosis lineage 4 genomes, the researchers calculated an average mutation rate and, based on that, dated the last common ancestor for the lineage to the late Roman period, somewhere around the year 450 CE. The mutation rate they calculated was consistent with a common ancestor of all M. tuberculosis lineages less than 6,000 years ago—a date that has been a point of contention in the TB field in recent years.

Next  the scientists recovered  Mycobacterium genome sequences,  from 1,000-year-old Peruvian human skeletons, that also pointed to a date for the most recent common ancestor of the M. tuberculosis complex of fewer than 6,000 years ago . The estimate of the common ancestor of the TB complex varies between 70,000 years and 6,000, so there’s a big difference. The discrepancy may result from the fact that mutation rate is not constant through time.

Everybody agrees—it’s been shown in different organisms that substitution rate should decay as you go further back in time, but we have just no idea [what] this decay actually looks like in M. tuberculosis. So there’s still a lot of work to be done to try to incorporate these uncertainties in a better way.

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with love 

-Dixy