Dormant Mycobacterium tuberculosis in the Brain: Insights from Human Autopsies and a Murine Model

This study aimed to detect dormant Mycobacterium tuberculosis inhuman brainstem tissue, trying to determine the bacterial metabolic state, analyzethe host transcriptomic responses, and comparing the findings with a murinelatency model. Brainstem tissue fragments from 50 forensic autopsies were testedfor the presence of M. tuberculosis specific transposon IS6110 sequence by PCR.In positive cases, RT-PCR was used to identify mycobacterial viability by theexpression of 16S rRNA and genes related to latency (DosT, DosR, icl, hspX), aswell as genes involved in metabolic adaptation (glcB, gcvB, pcaA, treS, phoP,mprA, kdpDE). Host transcriptomes were sequenced with the Illumina platform.Latent infection was also examined in a new murine model in BALB/c mice,analyzing the cerebral hemispheres with the same experimental approach.