Multidrug-resistant tuberculosis (MDR-TB), caused by drug resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. In this study, we examined a dataset of 5,310 M. tuberculosis whole genome sequences from five continents. Despite great diversity with respect to geographic point of isolation, genetic background and drug resistance, patterns of drug resistance emergence were conserved globally. We have identified harbinger mutations that often precede MDR. In particular, the katG S315T mutation, conferring resistance to isoniazid, overwhelmingly arose before rifampicin resistance across all lineages, geographic regions, and time periods. Molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of pre-MDR polymorphisms, particularly katG S315, into molecular diagnostics will enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

Non-coding RNAs are responsible for the regulation of many cell signaling pathways. These molecules include long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miR-NAs), which are involved in several biological processes such as apoptosis, mitochondrial dysfunction, and innate immunity. [6][7][8][9][10] lncRNAs are transcripts containing more than 200 nt, whose mechanisms of formation and function have been recently investigated. 11,12 According to some experimental studies, the differential expression of some lncRNAs has been found in cardiomyocytes, monocytes, and human tubular epithelial cells, when subjected to the addition of plasma obtained from septic patients, or, alternatively, the addition of pure lipopolysaccharide (LPS). [13][14][15] However, the function of these lncRNAs in sepsis still remains unclear. Human umbilical vein endothelial cells were screened for lncRNAs, and the results showed 28-to 70-fold increases in the expression of these non-coding RNAs after LPS exposure. 16 These changes could be involved in the modulation of inflammatory responses. For example, the lncRNA called lnc-IL7R

Introduction: This study aimed to determine first-line anti-tuberculosis drug resistance rates in new and previously treated cases and to identify risk factors associated with multidrug resistant tuberculosis (MDR-TB) at the National Reference Tuberculosis Laboratory of Iran. Methodology: This was a retrospective analysis of all confirmed TB patients from December 2000 to June 2005. Drug susceptibility testing to isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide was performed on Löwenstein-Jensen (LJ) medium according to the proportion method. Results: Mycobacterium tuberculosis strains were isolated from 1,742 patients with TB, of whom 935 (53.7%) were male. The mean age of patients was 44.2 ± 17.4 years (SD). A total of 1,074 patients were native Iranians while 668 (38.3%) were immigrant patients. Out of 1,139 (65.4%) new cases, 340 (29.9%) had at least one drug resistance. Of 603 (34.6%) previously treated cases, 416 (69.0%) had resistant strains. There were 263 patients (15.1%) with MDR-TB, 72 of whom were new (6.3% of all new cases) and 191 were previously treated (31.7% of all previously treated cases). Factors associated with MDR-TB included age under 45 years, male sex, previous TB treatment, immigration, poor living conditions, and unemployment. Conclusions: The high rate of initial resistance in MDR-TB cases and the high rate of MDR-TB in a young age group were indicators of recent transmission. Therefore, closer monitoring of transmission trends of drug resistant strains should be considered as priority, to ensure a successful TB control programme.