The Influence of HIV on the Evolution of Mycobacterium tuberculosis

One of the first studies to have investigate whether HIV influences the evolution of M. tuberculosis was recently published in Molecular Biology and Evolution by Anastasia Koch together with Prof Robert Wilkinson and A/Prof Darren Martin and other colleagues from the IDM, and the Swiss Tropical and Public Health Institute.  

The team conducted evolutionary analysis of M. tuberculosis full genome sequences isolated from HIV uninfected and HIV co-infected individuals living in Khayelitsha. Specific sites within M. tuberculosis genomes where the bacterium may have been compelled to evolve in response to HIV-1 coinfections were uncovered. Of significance was that when sites were classified according to their function, an unusually large number occurred in epitopes encoding regions.  

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 finding of some evidence for differential selection on epitope encoding regions was unexpected, but not totally counter-intuitive. Previous work by the Swiss 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.

While 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, the authors stress that the results must be validated on larger datasets before any broad conclusions can be drawn.

Their findings were published on the 21st of March 2017 in the advanced online edition of Molecular Biology and Evolution: https://doi.org/10.1093/molbev/msx107