English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background   PPE38  (Rv 2352c ) is a member of the large  PPE  gene family of  Mycobacterium tuberculosis  and related mycobacteria. The function of PPE proteins is unknown but evidence suggests that many are cell-surface associated and recognised by the host immune system. Previous studies targeting other  PPE  gene members suggest that some display high levels of polymorphism and it is thought that this might represent a means of providing antigenic variation. We have analysed the genetic variability of the  PPE38  genomic region on a cohort of  M. tuberculosis  clinical isolates representing all of the major phylogenetic lineages, along with the ancestral  M. tuberculosis  complex (MTBC) member  M. canettii , and supplemented this with analysis of publicly available whole genome sequences representing additional  M. tuberculosis  clinical isolates, other MTBC members and non tuberculous mycobacteria (NTM). Where possible we have extended this analysis to include the adjacent  plcABC  and  PPE39/40  genomic regions.    Results  We show that the ancestral MTBC  PPE38  region comprises 2 homologous  PPE  genes ( PPE38  and  PPE71 ), separated by 2  esat-6  ( esx )-like genes and that this structure derives from an  esx/esx/PPE  duplication in the common ancestor of  M. tuberculosis  and  M. marinum . We also demonstrate that this region of the genome is hypervariable due to frequent IS 6110  integration, IS 6110 -associated recombination, and homologous recombination and gene conversion events between  PPE38  and  PPE71 . These mutations result in combinations of gene deletion, gene truncation and gene disruption in the majority of clinical isolates. These mutations were generally found to be IS 6110  strain lineage-specific, although examples of additional within-lineage and even within-cluster mutations were observed. Furthermore, we provide evidence that the published  M. tuberculosis  H37Rv whole genome sequence is inaccurate regarding this region.    Conclusion  Our results show that this antigen-encoding region of the  M. tuberculosis  genome is hypervariable. The observation that numerous different mutations have become fixed within specific lineages demonstrates that this genomic region is undergoing rapid molecular evolution and that further lineage-specific evolutionary expansion and diversification has occurred subsequent to the lineage-defining mutational events. We predict that functional loss of these genes could aid immune evasion. Finally, we also show that the  PPE38  region of the published  M. tuberculosis  H37Rv whole genome sequence is not representative of the ATCC H37Rv reference strain.

Evidence for a rapid rate of molecular evolution at the hypervariable and immunogenic Mycobacterium tuberculosis PPE38 gene region