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Marine Natural Products and Drug Resistance in Latent Tuberculosis

1
Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad 44000, Pakistan
2
The State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
3
Department of Electrical Engineering, Capital University of Science and Technology, Islamabad 44000, Pakistan
4
College of Life Sciences, Chongqing Normal University, Chongqing 401331, China
5
Department of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(10), 549; https://doi.org/10.3390/md17100549
Received: 16 August 2019 / Revised: 5 September 2019 / Accepted: 6 September 2019 / Published: 26 September 2019
(This article belongs to the Special Issue Ion Channels as Marine Drug Targets)
Pyrazinamide (PZA) is the only drug for the elimination of latent Mycobacterium tuberculosis (MTB) isolates. However, due to the increased number of PZA-resistance, the chances of the success of global TB elimination seems to be more prolonged. Recently, marine natural products (MNPs) as an anti-TB agent have received much attention, where some compounds extracted from marine sponge, Haliclona sp. exhibited strong activity under aerobic and hypoxic conditions. In this study, we screened articles from 1994 to 2019 related to marine natural products (MNPs) active against latent MTB isolates. The literature was also mined for the major regulators to map them in the form of a pathway under the dormant stage. Five compounds were found to be more suitable that may be applied as an alternative to PZA for the better management of resistance under latent stage. However, the mechanism of actions behind these compounds is largely unknown. Here, we also applied synthetic biology to analyze the major regulatory pathway under latent TB that might be used for the screening of selective inhibitors among marine natural products (MNPs). We identified key regulators of MTB under latent TB through extensive literature mining and mapped them in the form of regulatory pathway, where SigH is negatively regulated by RshA. PknB, RshA, SigH, and RNA polymerase (RNA-pol) are the major regulators involved in MTB survival under latent stage. Further studies are needed to screen MNPs active against the main regulators of dormant MTB isolates. To reduce the PZA resistance burden, understanding the regulatory pathways may help in selective targets of MNPs from marine natural sources. View Full-Text
Keywords: marine anti-TB compounds; PZA; MTB; latent TB; sponges marine anti-TB compounds; PZA; MTB; latent TB; sponges
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Khan, M.T.; Kaushik, A.C.; Bhatti, A.I.; Zhang, Y.-J.; Zhang, S.; Wei, A.J.; Malik, S.I.; Wei, D.Q. Marine Natural Products and Drug Resistance in Latent Tuberculosis. Mar. Drugs 2019, 17, 549.

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