HIV drives evolution of tuberculosis bacterium

It is well known that antibiotics and vaccines affect the evolution of bacteria, often leading to treatment-resistant strains.

Now researchers have shown the bug responsible for TB, Mycobacterium tuberculosis, can evolve in response to HIV, a finding, they suggest, that could influence the design of TB vaccines for regions where HIV is endemic.

HIV and TB co-infection is very common. According to the World Health Organisation (WHO), out of 9.6 million new cases of TB in 2014, 1.2 million were people with HIV.

The current study was carried out by a team led by Anastasia Koch from the University of Cape Town, and is published in the journal Molecular Biology and Evolution.

The researchers’ hypothesis draws on Darwin’s theory of natural selection, which proposes that changes in the environment can favour or disadvantage certain characteristics of organisms. The researchers point out that by routing the unfortunate human host’s defences, HIV dramatically alters the immune environment of TB and plausibly introduces selection pressures.

To see if the TB bug did indeed evolve in that environment the researchers subjected 169 strains of M.tuberculosis to a technique called whole genome sequencing, which effectively determines the bacteria’s entire DNA sequence.

The samples came from people with and without HIV infection who took part in clinical trials in Khayelitsha, an impoverished township just outside of Cape Town, South Africa, between 2008 and 2010. At the time a third of adults in the area had HIV and there were 1500 new cases of TB per 100,000 people each year.

The mortal toll of TB is high. The WHO estimates TB killed 1.8 million people across the globe in 2015, 22% of whom were also infected with HIV.

In a world first, the researchers found three genetic regions of M.tuberculosis were evolving under the influence of HIV co-infection. Notably, those regions included ones coding for “epitopes”, which are the part of the bug the immune system sees as foreign and targets, raising the possibility that HIV-induced evolution could alter how M.tuberculosis reacts to human immunity.

This “may have implications for the design of M.tuberculosis vaccines that are intended for use in populations with high HIV-1 infection,” the authors conclude.

Commenting on the findings, Dr Nicholas West, head of TB research at the Australian Infectious Disease Research Centre in Queensland, says, “The authors have made some compelling arguments for HIV-induced genetic drift in M.tuberculosis, however, the relevance of this to the virulence of the bacteria is as yet unknown.

“One might conclude that these changes may have occurred due to a ‘relaxation’ of immune pressure as occurs due to HIV infection, allowing for expansion of these epitopes. It would be fascinating to know if these changes resulted in a stronger or weaker bacterium; I suspect the latter.”

According to West, if co-infection reduced the energy costs of living in the host, then infecting an HIV-positive person could be a plus for the TB bug.

“This work is an elegant reminder of the essential nature of the TB bacterium, that it is the quintessential survivor, and it again suggests this bug’s great success is due in part to its ability to adapt to its unique environment, the human host,” he adds.