Marine Natural Products and Drug Resistance in Latent Tuberculosis
Pyrazinamide (PZA) is the only drug for the elimination of latent <i>Mycobacterium tuberculosis</i> (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 (M...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/17/10/549 |
| _version_ | 1798003983980167168 |
|---|---|
| author | Muhammad Tahir Khan Aman Chandra Kaushik Aamer Iqbal Bhatti Yu-Juan Zhang Shulin Zhang Amie Jinghua Wei Shaukat Iqbal Malik Dong Qing Wei |
| author_facet | Muhammad Tahir Khan Aman Chandra Kaushik Aamer Iqbal Bhatti Yu-Juan Zhang Shulin Zhang Amie Jinghua Wei Shaukat Iqbal Malik Dong Qing Wei |
| author_sort | Muhammad Tahir Khan |
| collection | DOAJ |
| description | Pyrazinamide (PZA) is the only drug for the elimination of latent <i>Mycobacterium tuberculosis</i> (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. |
| first_indexed | 2024-04-11T12:16:17Z |
| format | Article |
| id | doaj.art-87a958f4930c474482e4647076551917 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T12:16:17Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-87a958f4930c474482e46470765519172022-12-22T04:24:18ZengMDPI AGMarine Drugs1660-33972019-09-01171054910.3390/md17100549md17100549Marine Natural Products and Drug Resistance in Latent TuberculosisMuhammad Tahir Khan0Aman Chandra Kaushik1Aamer Iqbal Bhatti2Yu-Juan Zhang3Shulin Zhang4Amie Jinghua Wei5Shaukat Iqbal Malik6Dong Qing Wei7Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad 44000, PakistanThe State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Electrical Engineering, Capital University of Science and Technology, Islamabad 44000, PakistanCollege of Life Sciences, Chongqing Normal University, Chongqing 401331, ChinaDepartment of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, ChinaDepartment of Immunology and Microbiology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, ChinaDepartment of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad 44000, PakistanThe State Key Laboratory of Microbial Metabolism, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaPyrazinamide (PZA) is the only drug for the elimination of latent <i>Mycobacterium tuberculosis</i> (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.https://www.mdpi.com/1660-3397/17/10/549marine anti-tb compoundspzamtblatent tbsponges |
| spellingShingle | Muhammad Tahir Khan Aman Chandra Kaushik Aamer Iqbal Bhatti Yu-Juan Zhang Shulin Zhang Amie Jinghua Wei Shaukat Iqbal Malik Dong Qing Wei Marine Natural Products and Drug Resistance in Latent Tuberculosis Marine Drugs marine anti-tb compounds pza mtb latent tb sponges |
| title | Marine Natural Products and Drug Resistance in Latent Tuberculosis |
| title_full | Marine Natural Products and Drug Resistance in Latent Tuberculosis |
| title_fullStr | Marine Natural Products and Drug Resistance in Latent Tuberculosis |
| title_full_unstemmed | Marine Natural Products and Drug Resistance in Latent Tuberculosis |
| title_short | Marine Natural Products and Drug Resistance in Latent Tuberculosis |
| title_sort | marine natural products and drug resistance in latent tuberculosis |
| topic | marine anti-tb compounds pza mtb latent tb sponges |
| url | https://www.mdpi.com/1660-3397/17/10/549 |
| work_keys_str_mv | AT muhammadtahirkhan marinenaturalproductsanddrugresistanceinlatenttuberculosis AT amanchandrakaushik marinenaturalproductsanddrugresistanceinlatenttuberculosis AT aameriqbalbhatti marinenaturalproductsanddrugresistanceinlatenttuberculosis AT yujuanzhang marinenaturalproductsanddrugresistanceinlatenttuberculosis AT shulinzhang marinenaturalproductsanddrugresistanceinlatenttuberculosis AT amiejinghuawei marinenaturalproductsanddrugresistanceinlatenttuberculosis AT shaukatiqbalmalik marinenaturalproductsanddrugresistanceinlatenttuberculosis AT dongqingwei marinenaturalproductsanddrugresistanceinlatenttuberculosis |