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Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants

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Abstract

Multidrug-resistant tuberculosis (MDR-TB) and TB–HIV co-infection have become a great threat to global health. However, the last truly novel drug that was approved for the treatment of TB was discovered 40 years ago. The search for new effective drugs against TB has never been more intensive. Natural products derived from microbes and medicinal plants have been an important source of TB therapeutics. Recent advances have been made to accelerate the discovery rate of novel TB drugs including diversifying strategies for environmental strains, high-throughput screening (HTS) assays, and chemical diversity. This review will discuss the challenges of finding novel natural products with anti-TB activity from marine microbes and plant medicines, including biodiversity- and taxonomy-guided microbial natural products library construction, target- and cell-based HTS, and bioassay-directed isolation of anti-TB substances from traditional medicines.

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Abbreviations

TB:

Tuberculosis

Mtb:

Mycobacterium tuberculosis

MDR-TB:

Multidrug-resistant Mycobacterium tuberculosis

XDR-TB:

Extensively drug-resistant TB

HIV:

Human immunodeficiency virus

NPL:

Natural products library

HTS:

High-throughput screening

PKS:

Polyketide synthases

NRPS:

Non-ribosomal peptide synthetases

ICL:

Isocitrate lyase

MS:

Malate synthase

BPL:

Biotin protein ligase

Fab:

Fatty acids biosynthase

MmpL:

Mycobacterial membrane protein, large

GyrB:

DNA gyrase subunit B

DHFR:

Dihydrofolate reductase

TMPK:

Thymidine monophosphate kinase

HRS:

High-resolution screening

ALIS:

Automated ligand identification system

rpsD:

Ribosomal protein small-subunit D

PtpA:

Protein tyrosine phosphatase A

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Acknowledgments

Part of this work was performed under research collaboration between the Global Alliance for TB Drug Development (TB Alliance) and the Institute of Microbiology of the Chinese Academy of Sciences (IMCAS). We acknowledge Drs. Zhenkun Ma, Anna Upton, and Christopher B. Cooper from the TB Alliance for their scientific input during the performance of this work. One of the authors, Krishna Bolla is thankful to TWAS & CAS for the financial support. This work was supported in part by grants from National Natural Science Foundation of China (81102369, 30911120483, 81102356, 30901849, 30973665, 30911120484), the CAS Pillar Program (XDA04074000) and the Ministry of Science and Technology of China (2011ZX11102-011-11, 2007DFB31620). LZ is an Awardee for National Distinguished Young Scholar Program in China.

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Authors and Affiliations

  1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100190, China

    Xueting Liu, Caixia Chen, Wenni He, Pei Huang, Miaomiao Liu, Qian Wang, Hui Guo, Krishna Bolla, Yan Lu, Fuhang Song, Huanqin Dai, Mei Liu & Lixin Zhang

  2. Graduate University of Chinese Academy of Sciences, Beijing, 100049, China

    Pei Huang, Miaomiao Liu, Qian Wang & Hui Guo

  3. Anhui University, Hefei, 230601, Anhui, China

    Yan Lu

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  1. Xueting Liu
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  9. Yan Lu
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  10. Fuhang Song
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  11. Huanqin Dai
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  12. Mei Liu
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  13. Lixin Zhang
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Corresponding author

Correspondence to Lixin Zhang.

Additional information

Xueting Liu and Caixia Chen have contributed equally to this paper.

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Liu, X., Chen, C., He, W. et al. Exploring anti-TB leads from natural products library originated from marine microbes and medicinal plants. Antonie van Leeuwenhoek 102, 447–461 (2012). https://doi.org/10.1007/s10482-012-9777-0

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  • DOI: https://doi.org/10.1007/s10482-012-9777-0

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