Recombinant M. tuberculosis Ag85A antigen [His]

Non-tuberculous mycobacteria cause a wide range of clinical disorders. Isoniazid (INH) and rifampin (RIF) are the most effective first-line antibiotics against for Mycobacterium tuberculosis. The aim of this study was to investigate the prevalence of mycobacteria in clinical samples collected during 8 years (2011-2018) in the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran and to determine the tuberculosis drug resistance to first-line antibiotics, INH and RIF. In this study, 15829 different clinical specimens were collected at the NRITLD National Tuberculosis Center. A multiplex allele specific polymerase chain reaction (MAS-PCR) was used to identify mutations related to RIF and INH resistance. The genes involved were katG315, inhA for INH and rpoB516, rpoB526 and rpoB531 for RIF. In total (7528/15829, 47.56%), mycobacterial isolates including 6937 MTBC (43.82%) and 591 NTM (3.73%) were obtained. The frequency of MTBC isolates decreased from 65.17% (2015/3092) in 2011 to 47.06% (1224/2601) in 2018. Among NTM isolates, M. simiae was the most prevalent with 55.33% (327/591). The average INH resistance ratio between 7528 MTB and NTM isolates was 21%, from 15.98% in 2011 to 18.76% in 2018. In the case of RIF, the same resistance trend has been gradually increasing from 12.45% in 2011 to 14.55% in 2018. The prevalence of MDR TB has increased during the study period, from 6.49% (134/2065) in 2011 to 12.58% (174/1354) in 2018. The results of this study indicate that early detection of mycobacterial strains and determination of their drug resistance are necessary.

Large genomic deletions (LGDs) (6 to 63 kbp) were observed in isoniazid-resistant Mycobacterium tuberculosis mutants derived from four M. tuberculosis strains. These LGDs had no growth defect in vitro but could be defective in intracellular growth and showed various sensitivities toward oxidative stress despite lacking katG. The LGD regions comprise 74 genes, mostly of unknown function, that may be important for M. tuberculosis intracellular growth and protection against oxidative stress.