Marine Natural Products and Drug Resistance in Latent Tuberculosis

• Published in: Marine drugs 2019-09, Vol.17 (10), p.549
• Main Authors: Khan, Muhammad Tahir, Kaushik, Aman Chandra, Bhatti, Aamer Iqbal, Zhang, Yu-Juan, Zhang, Shulin, Wei, Amie Jinghua, Malik, Shaukat Iqbal, Wei, Dong Qing
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Antitubercular Agents - therapeutic use; Biological Products - therapeutic use; Biology; DNA-directed RNA polymerase; Dormancy; Drug resistance; Drug Resistance - drug effects; Drugs; Gene expression; HIV; Human immunodeficiency virus; Humans; Hypoxia; latent tb; Latent Tuberculosis - drug therapy; marine anti-tb compounds; Marine invertebrates; Metabolites; Microbial Sensitivity Tests - methods; mtb; Mutation - drug effects; Mycobacterium tuberculosis - drug effects; Natural products; Oxidative stress; Pathogens; Phosphorylation; Proteins; Pyrazinamide; Pyrazinamide - therapeutic use; pza; Review; RNA polymerase; Signal transduction; sponges; Survival; Tuberculosis
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17100549

Pyrazinamide (PZA) is the only drug for the elimination of latent (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.