Effect of an Oxadiazoline and a Lignan on Mycolic Acid Biosynthesis and Ultrastructural Changes of Mycobacterium tuberculosis
نویسندگان
چکیده
Tuberculosis (TB) is an important disease that causes thousands of deaths around the world. Resistance against antitubercular available drugs has been reported; so, research on new effective antimycobacterial molecules is needed. Antimycobacterial activity of three lignans and two synthetic hydrazones was assessed against Mycobacterium tuberculosis H37Rv by antimycobacterial microdilution assay (TEMA). An oxadiazoline (AC451) and a lignan (ethoxycubebin) were the most active compounds (MIC 6.09 and 62.4 μM, resp.). Several changes in mycolic acid profile of treated bacteria were detected with both compounds by mass spectrometry analysis. Additionally, the level of reduction of mycolic acids in ethoxycubebin treatment was correlated to disruption in bacterial morphology.
منابع مشابه
Mycobacterium tuberculosis Des protein: an immunodominant target for the humoral response of tuberculous patients.
The phoA gene fusion methodology permitted the identification of a new Mycobacterium tuberculosis exported protein, Des. This protein has significant sequence similarities to plant acyl-acyl carrier protein desaturases, which are enzymes involved in general fatty acid biosynthesis as well as in mycolic acid biosynthesis in mycobacteria. As shown by Western blot and enzyme-linked immunosorbent a...
متن کاملInterpreting Expression Data with Metabolic Flux Models: Predicting Mycobacterium tuberculosis Mycolic Acid Production
Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these ...
متن کاملDetermination of the primary target for isoniazid in mycobacterial mycolic acid biosynthesis with Mycobacterium aurum A+.
The target of the potent antituberculosis drug isoniazid was investigated in Mycobacterium aurum A+, against which isoniazid has an MIC (the minimum concentration required to give growth inhibition) of 0.3 microgram/ml. Mycolic acid biosynthesis, measured by the incorporation of label from [1-14C]acetate into mycolic acids, was inhibited differentially by isoniazid in cell-wall preparations of ...
متن کاملMycolic acids: deciphering and targeting the Achilles' heel of the tubercle bacillus
Mycolic acids are unique long chain fatty acids found in the lipid-rich cell walls of mycobacteria including the tubercle bacillus Mycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development. This is particularly relevant to the impact on global health given the rise of multidrug resistant ...
متن کاملThe mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance.
A target of the anti-tuberculosis drugs isoniazid (INH) and ethionamide (ETH) has been shown to be an enoyl reductase, encoded by the inhA gene. The mabA (mycolic acid biosynthesis A) gene is located immediately upstream of inhA in Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium smegmatis. The MabA protein from M. tuberculosis was expressed in Escherichia coli and shown to hav...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
دوره 2011 شماره
صفحات -
تاریخ انتشار 2011