Recombinant M. Tuberculosis MT3413 Antigen [His, GST]

Toxin-antitoxin systems are widespread stress-responsive elements, many of whose functions remain largely unknown. Here, we characterize the four DUF1814-family nucleotidyltransferase-like toxins (MenT(1-4)) encoded by the human pathogen Mycobacterium tuberculosis. Toxin MenT(3) inhibited growth of M. tuberculosis when not antagonized by its cognate antitoxin, MenA(3). We solved the structures of toxins MenT(3) and MenT(4) to 1.6 and 1.2 A resolution, respectively, and identified the biochemical activity and target of MenT(3). MenT(3) blocked in vitro protein expression and prevented tRNA charging in vivo. MenT(3) added pyrimidines (C or U) to the 3'-CCA acceptor stems of uncharged tRNAs and exhibited strong substrate specificity in vitro, preferentially targeting tRNA(ser) from among the 45 M. tuberculosis tRNAs. Our study identifies a previously unknown mechanism that expands the range of enzymatic activities used by bacterial toxins, uncovering a new way to block protein synthesis and potentially treat tuberculosis and other infections.

Objectives. - Inflammatory disorders of the parathyroid gland are poorly defined. Only seven cases of granulomatous infection have been reported in the literature. Patients and methods. - A 68-year-old woman presented with parathyroid hormone level at 277 pg/mL and calcium level at 10.8 mg/dL, considered as primary hyperparathyroidism. Parathyroidectomy was performed, normalizing analytical values. Results. - Normal-size gland with chief cell hyperplasia, focal pseudofollicular changes, and presence of epithelioid granulomas with Langhans giant cells and caseous necrosis areas, and a positive PCR for M. tuberculosis complex was identified. Chronic granulomatous inflammation could provoke a cascade of immune system activation, resulting in hyperplasia with the consequent increase in parathyroid function, and therefore primary hyperparathyroidism. Conclusions. - In populations with a high incidence of tuberculosis, the coexistence of these pathologies must be kept in mind. This theory needs further biomolecular studies to be confirmed, but it provides a new perspective within the possible etiologies of hyperparathyroidism. (C) 2020 Elsevier Masson SAS. All rights reserved.