Hypervirulent TB Strain Evolved in Northern China 2,000 Years Ago

The dominant TB strain circulating in East Asia has had a long history and is unlikely to have been caused by recent vaccination and treatment efforts.

AsianScientist (Jun. 30, 2015) – The most virulent strains of Mycobacterium tuberculosis evolved in Northern China during the Neolithic period and were disseminated by Han Chinese migration, according to research published in the Proceedings of the National Academy of Science.

Throughout human history, tuberculosis (TB) has surfaced and receded as a highly infectious disease that causes unpredictable great epidemics and heavy casualties. According to the World Health Organisation, approximately one-third of the world’s current population harbors undetectable latent TB, and have a 5-10 percent chance of it activating during their lifetime. Once activated, TB is very contagious and can be easily transmitted from a person with active TB through coughing, sneezing or laughing.

It is commonly believed that TB emerged during human migration from Africa approximately 70,000 years ago. Among the seven main M. tuberculosis complex (MTBC) phylogenetic lineages, the most predominant lineage in East Asia is Lineage 2, from which the Beijing family descended.

In the present study led by Professor Qian Gao from Fudan University, a team of researchers from China, Spain and Switzerland traced the evolutionary origins and dissemination of the Beijing family, a strain that is responsible for emerging outbreaks of antibiotic-resistant TB around the world.

To trace the spatiotemporal origins of the Beijing family strains, the team of researchers conducted whole genome sequencing and single nucleotide polymorphism (SNP) analysis of 95 clinical strains isolated from China and of 263 genomes from 15 other countries.

Based on genomic markers and deletions, they constructed a phylogenetic tree of Lineage 2 MTBC that enabled them to identify the ancestral strains of the Beijing family, ‘proto-Beijing’, and classify the Beijing family strains into ‘ancient’ and ‘modern’ subtypes.

By estimating the age of the substrains and matching patient locations with phylogenetic data, the researchers showed that the proto-Beijing strain predominantly surfaced in patients born in Southern China and Southeast Asia but not in Northern China. These findings indicate a southern origin for Lineage 2 and the three Beijing subtypes, which likely occurred 30,000 years ago during Neolithic human migration into East Asia, in agreement with anthropological evidence for early human migration from Africa into East Asia and upwards into northern China and Siberia.

During the agricultural revolution, wide-scale adoption of intensive agriculture in place of the hunter-gatherer lifestyle enabled the settling and growth of human populations in what is known as the Neolithic Demographic Transition (NDT). From estimating the age, population sizes and geographical distribution of Lineage 2 strains, the researchers traced a massive expansion of strains just prior to the NDT.

Although the three major Beijing strains were disseminated all over China with the exception of Tibet, modern-Beijing was the most prevalent strain, and the timing of its expansion most closely matched the dates of the NDT era in Northern China. The authors propose that selection of modern-Beijing as the dominant subtype in Northern China occurred due to it gaining stronger virulence while co-evolving with dense populations of Neolithic humans.

Indeed, the hypervirulence of modern-Beijing has been demonstrated by studies showing greater mortality in mice infected with modern-Beijing compared to ancient-Beijing, and the higher frequency of modern-Beijing found in patients with bacillus Calmette-Guérin (BCG) vaccinations.

After its successful evolution, modern-Beijing was then carried with the wave of Han Chinese migration back into Southern China about 2,000 years ago. It has since surfaced in outbreaks around the globe such as in Cuba, South Africa and countries of the former Soviet Union.

This study challenges previous hypotheses of an East Asian origin and recent dominance of the Beijing family through resistance against BCG vaccinations and anti-TB drugs. Instead, the authors postulate a southern east Asian origin, and suggest that modern-Beijing became highly contagious and gained virulence to adapt to dense human populations, long before the use of vaccination and antibiotic treatments.

While endemic strains within East Asia remain diverse, the hypervirulent homogenous modern-Beijing family has surfaced globally in recent TB outbreaks. With the advent of AIDS and higher frequency of immunocompromised individuals, it is increasingly important to understand the selection forces and factors that contribute to the spread and virulence of modern-Beijing.

Knowing the geographic history of TB strains would also aid with transmission surveillance and speed the investigation of likely sources of TB outbreaks. It would also inform the appropriate use of countermeasures such as vaccinations and anti-TB drugs that may or may not be effective against a particular strain of TB that is likely to be prevalent in the region.

The article can be found at: Luo et al. (2015) Southern East Asian Origin And Coexpansion Of Mycobacterium tuberculosis Beijing Family With Han Chinese.

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Copyright: Asian Scientist Magazine; Photo: NIAID/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Juliana is completing her PhD on novel human macrophage immune mechanisms at The University of Queensland. She interned at the tech transfer company, UniQuest, and volunteers as a science writer and editor. In her spare time Juliana loves creative writing, studying languages and exploring new places.

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