Mouse Anti-M. tuberculosis 38kDa Monoclonal antibody, clone ITM2

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.

Mycobacterium tuberculosis causes human tuberculosis, and a better understanding of its biology is required to identify vulnerabilities that might be exploited in developing new therapeutics. The iron-sulfur cluster of the essential M. tuberculosis central metabolic enzyme, aconitase (AcnA), disassembles when exposed to oxidative/nitrosative stress or iron chelators. The catalytically inactive apo-AcnA interacts with a sequence resembling an iron-responsive element (IRE) located within the transcript of another essential protein, CwlM, a regulator of peptidoglycan synthesis. A Mycobacterium smegmatis cwlM conditional mutant complemented with M. tuberculosis cwlM with a disrupted IRE is unable to recover from combinations of oxidative, nitrosative, and iron starvation stresses. An equivalent M. tuberculosis cwlM conditional mutant complemented with the cwlM gene lacking a functional IRE exhibits a growth defect in THP-1 macrophages. It appears that AcnA acts to couple peptidoglycan synthesis and central metabolism, and disruption of this coupling potentially leaves mycobacteria vulnerable to attack by macrophages.