Addressing diversity in tuberculosis using multidimensional approaches

Abstract

Tuberculosis is a complex disease, which can affect many organs other than the lungs. Initial infection may be cleared without inducing immunological memory, or progress directly to primary disease. Alternatively, the infection may be controlled as latent TB infection, that may progress to active tuberculosis at a later stage. There is now a greater understanding that these infection states are part of a continuum, and studies using PET/CT imaging have shown that individual lung granulomas may respond to infection independently, in an un-synchronized manner. In addition, the Mycobacterium tuberculosis organisms themselves can exist in different states: as nonculturable forms, as 'persisters', as rapidly growing bacteria and a biofilm-forming cording phenotype. The 'omics' approaches of transcriptomics, metabolomics and proteomics can help reveal the mechanisms underlying these different infection states in the host, and identify biosignatures with diagnostic potential, that can predict the development of disease, in 'progressors' as early as 12-18 months before it can be detected clinically, or that can monitor the success of anti-TB therapy. Further insights can be obtained from studies of BCG vaccination and new TB vaccines. For example, epigenetic changes associated with trained immunity and a stronger immune responses following BCG vaccination can be identified. These omics approaches may be particularly valuable when linked to studies of mycobacterial growth inhibition, as a direct read-out of the ability to control mycobacterial growth. The second generation of omics studies is identifying much smaller signatures based on as few as 3 or 4 genes. Thus, narrowing down omics-derived biosignatures to a manageable set of markers now opens the way to field-friendly point of care assays.

DNA methylomes derived from alveolar macrophages display distinct patterns in latent tuberculosis - implication for interferon gamma release assay status determination

“…Biosignatures of TB have been proposed to lay ground for next generation of diagnostics for TB 27,28 and accumulating literature have been published studying possible TB biosignatures, based on e.g., global methylation analysis, transcriptional profiling and RNA sequencing enrichment 29-32 . However, no biomarker or signature of active or latent TB has been successful when generalized or applied in larger sample sizes and biosignature based diagnostics tools are still unavailable in the clinic.…”

A TB free India is far away

“…Tuberculosis (TB) is a complicated disease affecting not only the respiratory organ but also eyes, bones and gut etc. 1 It is caused by a pathogen, Mycobacterium. In the world there are millions of pathogens.…”

DNA methylomes derived from alveolar macrophages and alveolar T cells display distinct patterns in tuberculosis – a future precision tool for TB status determination?

“…Biosignatures of TB have been proposed to lay ground for next generation of diagnostics for TB and accumulating literature have been published studying possible TB biosignatures [10,11]. DNAm based biosignatures exists for many other conditions including in ammatory arthritis and asthma [12,13].…”