Where did drug-resistant TB come from?

A reconstruction of the evolutionary history and genetic basis for the massive spread of multidrug resistance in tuberculosis (TB) indicates that increases in the population size of this pathogen coincided with the Industrial Revolution and the collapse of the Soviet Union.

TB, a contagious bacterial infection caused by Mycobacterium tuberculosis, continues to pose a serious health threat and is responsible for 1.5 million deaths worldwide each year.

Specific strains of M. tuberculosis, such as those of the Beijing lineage, have acquired resistance to multiple antibiotics and play an important role in driving the massive spread of multidrug-resistant TB in Eurasia.

This international study conducted genetic analysis of almost 5000 isolates of strains of the Beijing lineage from 99 countries, as well as whole genome sequencing of 110 isolates, to better understand how this lineage has evolved its multidrug resistance over time.

The results showed that this lineage, which was first identified in Beijing in the mid-1990s, originated in northeastern China, Japan and Korea about 6600 years ago. Sublineages of the pathogen then radiated worldwide in several waves accompanied by successive increases in population size, in particular over the last 200 years.

The research showed that these increases in population size practically coincided with the Industrial Revolution, the First World War and HIV epidemics. A drop in population size coincided with the rise of antibiotic use in the 1960s.

The spread of two multidrug-resistant clones of this lineage was traced throughout central Asia and Russia to the early 1990s when the public health system of the former Soviet Union collapsed.

Although, as the authors state, the exact timing remains dependent on uncertainties in mutation rates, the parallels between changes in the bacterial population and these key events in human history is intriguing.

The researchers also identified mutations in 15 genes that may have contributed to drug resistance in the Beijing lineage.

Further work to determine the genes (and mutations) contributing to the expansion of these modern Beijing strains may lead to new targets being found to tackle tuberculosis.

The study has been published in a paper published in Nature Genetics.