The Influence of HIV on the Evolution of Mycobacterium tuberculosis

Abstract

HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates.

Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production

“…Genomic variants were annotated with SnpEff 52 v4.3t according to the M. tuberculosis H37Rv reference genome annotation (NC_000962.3; GCF_000195955.2). To minimize false positives, previously identified repetitive genomic regions, mobile elements and genes containing ≥50 bp nucleotide chunks identical to other parts of the genome 53,54 were not considered to further analysis. Variants exclusive from either low or high IL-1β-inducing strains were assigned only on sites that had the reference allele successfully called on all the isolates belonging to the opposite phenotype.…”

Multiple Introductions of Mycobacterium tuberculosis Lineage 2–Beijing Into Africa Over Centuries

“…We obtained whole-genome sequencing data of L2 strains from the two previously largest studies focusing on the evolutionary history and global spread of L2-Beijing strains (Luo et al, 2015;Merker et al, 2015). We then identified additional published genomes as African and non-African representatives of L2-Beijing strains from other studies (Comas et al, 2010(Comas et al, , 2013Casali et al, 2012Casali et al, , 2014Kato-Maeda et al, 2012;Zhang et al, 2013;Portevin et al, 2014;Guerra-Assunção et al, 2015;Koch et al, 2017;Manson et al, 2017). Moreover, we newly sequenced 116 additional L2-Beijing strains using Illumina HiSeq 2000/2500 paired end technology (PRJNA488343).…”

GenomegaMap: within-species genome-widedN/dSestimation from over 10,000 genomes

“…Such studies can benefit from an understanding of the selection pressures shaping genetic diversity and the identification of sites under positive selection because often that selection is driven by drug therapy (e.g. Pepperell et al 2013;Zhang et al 2013;Farhat et al 2013;Osório et al 2013;Lee et al 2015;Koch et al 2017;Mortimer et al 2018).…”