Could HIV co-infection influence how tuberculosis evolves?

Researchers have analyzed the genome of Mycobacteria tuberculosis, demonstrating the HIV co-infection could influence how M. tuberculosis evolves via an altered immune environment.

It is known that co-infection with HIV makes individuals more susceptible to TB infection – these patients often suffer severe complications and have higher mortality rates. This study, published recently in Molecular Biology and Evolution, hypothesized that HIV co-infections create altered host immunological environments thereby influencing the evolution of M. tuberculosis.

The team collected samples from individuals in Khayelitsha (South Africa), a community in Cape Town with among the highest HIV and TB rates in the world, and carried out an evolutionary analysis of the M. tuberculosis full genome sequences.

They compared bacteria from HIV uninfected and HIV co-infected individuals, discovering specific sites in the M. Tuberculosis genomes where the bacteria may have evolved in response to HIV co-infection.

Author Anastasia Koch (University of Cape Town, South Africa) explained: “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.”

The researchers then classified the sites they had identified, and discovered that large numbers of these sites occurred in regions of the genome coding for epitopes. Koch expanded: “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.”

Although more research is needed, the authors hope their findings will inform perceptions around the potential of M. tuberculosis to evolve in response to interventions, such as antibiotics and vaccines, but also to largely uncontrollable factors such as co-infections or microbial communities present in the host.

Koch concluded: “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.”

Sources: Kock A, Brites D, Stucki D et al. The Influence of HIV on The Evolution of Mycobacterium Tuberculosis. Mol. Biol. Evol. doi:10.1093/molbev/msx107 (2017) (Epub ahead of print);


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