Nav: Home

HIV co-infection influences natural selection on M. tuberculosis

March 21, 2017

Tuberculosis (TB) remains a major global health problem, with 10 million cases and 2 million deaths per year, according to the World Health Organization. The only available vaccine is effective in children but its effect wanes in older children and adults.

Persons co-infected with HIV are more susceptible to TB infection, often encounter severe complications and experience a much higher mortality rate. The brunt of the co-epidemic is felt in Sub-Saharan Africa, a region with concomitantly high rates of poverty and inequality. While M. tuberculosis has been evolving with humans for thousands of years, HIV co-infections create host immunological environments that this bacterium has not encountered before and could, therefore, be nudging it to evolve new characteristics.

In one of the first studies to have investigated this hypothesis, an evolutionary analysis of M. tuberculosis full genome sequences from HIV uninfected and HIV co-infected individuals was conducted by Anastasia Koch, together with Prof Robert Wilkinson and Dr. Darren Martin and other colleagues from Cape Town, South Africa and Basel, Switzerland. These M. tuberculosis strains were isolated from individuals living in Khayelitsha, a Cape Town community with among the highest HIV and TB rates in the world.

The research team uncovered specific sites within M. tuberculosis genomes where the bacterium may have been compelled to evolve in response to HIV-1 co-infections. Of particular significance was that when sites were classified according to their function, an unusually large number occurred in parts of the M. tuberculosis genome that code for epitopes: parts of M. tuberculosis proteins that are recognized by human B and T cells, however in this study only epitopes that might be recognized by T cells were investigated.

"This is the first time that phylogenetically informed and statistically sophisticated evolutionary models have been applied to M. tuberculosis whole genome sequence data to detect codon site specific natural selection that might be influenced by HIV co-infection. An important finding of this work is that natural selection on M. tuberculosis codons can be detected using these methods, and that HIV may be impacting how M. tuberculosis is presently evolving." said Koch. "The finding of some evidence for differential selection on epitope encoding regions was unexpected, but not totally counter-intuitive. Previous work by our collaborators has established unusual levels of M. tuberculosis epitope conservation in HIV uninfected individuals, which suggests that, in the absence of HIV, epitope conservation is favourable for M. tuberculosis. HIV co-infection may disrupt the relationship between host and bacillus, and thus decreases the favourability of epitope conservation."

"It is also highly desirable that our results are validated on larger datasets in other disease settings to establish how generalizable our findings are; especially since the influence of HIV on M. tuberculosis epitope evolution could have implications for the design of vaccines to be administered in settings with high rates of HIV-associated TB."

Koch hopes that the work will inform thinking around the potential for M. tuberculosis to evolve not just in response to human interventions such as the antibiotics or vaccines that have been used to control this bacterium, but also in response to the largely uncontrollable and ever-changing microbial communities that share humans as their preferred homes.

Their findings appear in the advanced online edition of Molecular Biology and Evolution.
-end-


Molecular Biology and Evolution (Oxford University Press)

Related Tuberculosis Articles:

Tuberculosis: New insights into the pathogen
Researchers at the University of W├╝rzburg and the Spanish Cancer Research Centre have gained new insights into the pathogen that causes tuberculosis.
Unmasking the hidden burden of tuberculosis in Mozambique
The real burden of tuberculosis is probably higher than estimated, according to a study on samples from autopsies performed in a Mozambican hospital.
HIV/tuberculosis co-infection: Tunneling towards better diagnosis
1.2 million people in the world are co-infected by the bacteria which causes tuberculosis and AIDS.
Reducing the burden of tuberculosis treatment
A research team led by MIT has developed a device that can lodge in the stomach and deliver antibiotics to treat tuberculosis, which they hope will make it easier to cure more patients and reduce health care costs.
Tuberculosis: Commandeering a bacterial 'suicide' mechanism
The bacteria responsible for tuberculosis can be killed by a toxin they produce unless it is neutralized by an antidote protein.
A copper bullet for tuberculosis
Tuberculosis is a sneaky disease, and the number one cause of death from infectious disease worldwide.
How damaging immune cells develop during tuberculosis
Insights into how harmful white blood cells form during tuberculosis infection point to novel targets for pharmacological interventions, according to a study published in the open-access journal PLOS Pathogens by Valentina Guerrini and Maria Laura Gennaro of Rutgers New Jersey Medical School, and colleagues.
How many people die from tuberculosis every year?
The estimates for global tuberculosis deaths by the World Health Organisation (WHO) and the Institute for Health Metrics and Evaluation (IHME) differ considerably for a dozen countries, according to a study led by ISGlobal.
Beyond killing tuberculosis
Historically, our view of host defense against infection was that we must eliminate pathogens to eradicate disease.
Tuberculosis drugs work better with vitamin C
Studies in mice and in tissue cultures suggest that giving vitamin C with tuberculosis drugs could reduce the unusually long time it takes these drugs to eradicate this pathogen.
More Tuberculosis News and Tuberculosis Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.