M. Tuberculosis ESAT-6 Antigen (DAGA-187)

M. Tuberculosis ESAT-6 Antigen, Recombinant protein from E. coli for WB, ELISA

Product Overview
N-terminal GST fusion protein with C-terminal 6xHis fusion protein of antigen ESAT-6(Rv3875) (M. Tuberculosis/H37Rv) (a.a.1-99) (Genbank Accession No. NP_217552). Early secretory antigenic target (see citations below), identical to Q57165|O84901| ESAT6 early secretory antigenic target from Mycobacterium bovis (94 aa). A core mycobacterial gene; conserved in mycobacterial strains. Predicted possible vaccine candidate.
Nature
Recombinant
Tag/Conjugate
GST, His
Alternative Names
M. Tuberculosis 63 kDa protein; Mycobacterium tuberculosis 99 kDa protein; Mycobacterium tuberculosis; M. tuberculosis; MTB; TB antigen
Procedure
None
Purity
>95% , based on SDS PAGE
Format
Each vial contains 100 µg of lyophilized protein in PBS with 8M Urea.
Concentration
Batch dependent - please inquire should you have specific requirements.
Size
1000ug, 1mg
Preservative
None
Reconstitution
Reconstitute the protein with 100 µl of Millipore water.
Antigen Description
Mycobacterium tuberculosis is an obligate pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of tuberculosis First discovered in 1898 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface (primar
Keywords
M. Tuberculosis 63 kDa protein;Mycobacterium tuberculosis 99 kDa protein;Mycobacterium tuberculosis;M. tuberculosis;MTB;TB antigen

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References


Cyclic Peptide [R4W4] in Improving the Ability of First-Line Antibiotics to InhibitMycobacterium tuberculosisInsidein vitroHuman Granulomas

FRONTIERS IN IMMUNOLOGY

Authors: Hernandez, Joshua; Ashley, David; Cao, Ruoqiong; Abrahem, Rachel; Nguyen, Timothy; To, Kimberly; Yegiazaryan, Aram; David, Ajayi Akinwale; Tiwari, Rakesh Kumar; Venketaraman, Vishwanath

Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains ofMycobacterium tuberculosis(M. tb) that are difficult to treat. A current therapeutic strategy attempting to circumvent this issue aims to enhance drug delivery to reduce the duration of the antibiotic regimen or dosage of first-line antibiotics. One such agent that may help is cyclic peptide [R4W4], as it has been shown to have antibacterial properties (in combination with tetracycline) against methicillin-resistantStaphylococcus aureus(MRSA) in the past. The objective of this study is to test cyclic peptide [R4W4] both alone and in combination with current first-line antibiotics (either isoniazid or pyrazinamide) to study the effects of inhibition ofM. tbinsidein vitrohuman granulomas. Results from our studies indicate that [R4W4] is efficacious in controllingM. tbinfection in the granulomas and has enhanced inhibitory effects in the presence of first-line antibiotics.

OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Authors: Hariguchi, Norimitsu; Chen, Xiuhao; Hayashi, Yohei; Kawano, Yoshikazu; Fujiwara, Mamoru; Matsuba, Miki; Shimizu, Hiroshi; Ohba, Yoshio; Nakamura, Izuru; Kitamoto, Ryuki; Shinohara, Toshio; Uematsu, Yukitaka; Ishikawa, Shunpei; Itotani, Motohiro; Haraguchi, Yoshikazu; Takemura, Isao; Matsumoto, Makoto

There is an urgent need for new, potent antituberculosis (anti-TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3,4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent antituberculosis activity. The MICs of the compound for Mycobacterium tuberculosis ranged from 0.00024 to 0.002 mu g/ml. It had bactericidal activity against both growing and intracellular bacilli, and the frequency of spontaneous resistance for M. tuberculosis H37Rv was less than 1.91 x 10(-7). It did not show antagonistic effects with other anti-TB agents in an in vitro checkerboard assay. Whole-genome and targeted sequencing of isolates resistant to OPC-167832 identified decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1), an essential enzyme for cell wall biosynthesis, as the target of the compound, and further studies demonstrated inhibition of DprE1 enzymatic activity by OPC-167832. In a mouse model of chronic TB, OPC-167832 showed potent bactericidal activities starting at a dose of 0.625 mg/kg of body weight. Further, it exhibited significant combination effects in 2-drug combinations with delamanid, bedaquiline, or levofloxacin. Finally, 3- or 4-drug regimens comprised of delamanid and OPC-167832 as the core along with bedaquiline, moxifloxacin, or linezolid showed efficacy in reducing the bacterial burden and preventing relapse superior to that of the standard treatment regimen. In summary, these results suggest that OPC-167832 is a novel and potent anti-TB agent, and regimens containing OPC-167832 and new or repurposed anti-TB drugs may have the potential to shorten the duration of treatment for TB.

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