In vitro evaluation of dinactin,a potent microbial metabolite against Mycobacterium tuberculosis |
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Authors: | Aehtesham Hussain Muzafar Ahmad Rather Zubair Shanib Bhat Aasif Majeed Mubashir Maqbool Aabid Manzoor Shah Mushtaq A Aga Aiyatullah Shah Saleem Mushtaq Payare L Sangwan Qazi Parvaiz Hassan Zahoor Ahmad |
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Institution: | 1. Microbial Biotechnology Division, CSIR – Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India;2. Academy of Scientific and Innovative Research, CSIR – Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, 180001, India;3. Clinical Microbiology and PK/PD Division, CSIR – Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India;4. Bio-organic chemistry division, CSIR – Indian Institute of Integrative Medicine, Sanatnagar, Srinagar, Jammu & Kashmir 190005, India;5. Bio-organic chemistry division, CSIR – Indian Institute of Integrative Medicine, Jammu Tawi, 180001, India |
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Abstract: | Current long duration treatment options and the emergence of drug resistance in tuberculosis (TB) have led to renewed interest in discovery of novel anti-tubercular agents or the scaffolds exhibiting enhanced efficacy with current anti-TB drugs. Herein, dinactin, a potent bioactive macrotetrolide isolated from Streptomyces puniceus AS13, was evaluated against Mycobacterium tuberculosis H37Rv and other susceptible and drug-resistant clinical isolates of M. tuberculosis. In vitro pharmacological assays showed that dinactin is bactericidal against laboratory standard strain M. tuberculosis H37Rv (minimum inhibitory concentration MIC] 1 µg/mL and minimum bactericidal concentration MBC] 4 µg/mL). Dinactin also retained its activity against various clinical isolates, including multidrug-resistant strains of M. tuberculosis. Whole cell interaction assays with standard first- and second-line anti-TB drugs showed the synergistic interaction of dinactin with rifampicin or amikacin, reflecting its suitability for use in combination regimens. The killing kinetics studies of dinactin against M. tuberculosis H37Rv revealed that it has strong concentration-dependent anti-TB activity that is also dependent on time. The kill curve also showed dynamic killing capacity of dinactin as it exhibited bactericidal potential at all concentrations tested. Kill curve data demonstrated that dinactin, like isoniazid, exerts its strong tuberculocidal activity within the first two days of exposure. This evidence strongly supports further evaluation of dinactin as a new option in the treatment of TB. |
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Keywords: | Tuberculosis Dinactin Bactericidal Synergism Kill Kinetics |
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