Cordycepin kills Mycobacterium tuberculosis through hijacking the bacterial adenosine kinase

PloS One
Feng HuangZheng-Guo He

Abstract

Cordycepin is an efficient component of Cordyceps spp, a traditional Chinese medicine widely used for healthcare in China, and has been recently acted as a strong anticancer agent for clinic. However, whether and how it may play a role in combating tuberculosis, caused by Mycobacterium tuberculosis, remains unknown. Here we report that cordycepin can kill Mycobacterium by hijacking the bacterial adenosine kinase (AdoK), a purine salvage enzyme responsible for the phosphorylation of adenosine (Ado) to adenosine monophosphate (AMP). We show that cordycepin is a poor AdoK substrate but it competitively inhibits the catalytic activity of AdoK for adenosine phosphorylation. Cordycepin does not affect the activity of the human adenosine kinase (hAdoK), whereas hAdoK phosphorylates cordycepin to produce a new monophosphate derivative. Co-use of cordycepin and deoxycoformycin, an inhibitor of adenosine deaminase (ADD), more efficiently kills M. bovis and M. tuberculosis. The add-deleted mycobacterium is more sensitive to cordycepin. This study characterized cordycepin as a new mycobactericidal compound and also uncovered a potential anti-mycobacterial mechanism.

References

Jan 1, 1976·Archives of Virology·K Hashimoto, B Simizu
Feb 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·J SpychalaB S Mitchell
Jun 13, 1998·Antimicrobial Agents and Chemotherapy·A M Sugar, R P McCaffrey
Feb 27, 2001·Medicinal Research Reviews·G CristalliE Camaioni
Oct 26, 2002·European Journal of Pharmacology·Xiaoxia ZhouFred Zepp
Oct 18, 2003·The Journal of Antimicrobial Chemotherapy·Esther W BarrowWilliam W Barrow
Nov 5, 2003·Journal of Bacteriology·Mary C LongWilliam B Parker
Oct 13, 2006·Cancer Chemotherapy and Pharmacology·Wei-Ciao WuBu-Miin Huang
Dec 13, 2006·Journal of Medicinal Chemistry·Steven W MuchmoreClarissa L Jakob
Mar 10, 2007·Current Pharmaceutical Design·William B Parker, Mary C Long
Jun 15, 2007·Cancer Chemotherapy and Pharmacology·Hellinida ThomadakiAndreas Scorilas
Jan 22, 2008·British Journal of Haematology·Lisa S ChenVarsha Gandhi
Dec 20, 2013·Nature Communications·Shichun LunWilliam R Bishai
Jul 11, 2015·Nature Communications·Jan RybnikerStewart T Cole
Oct 11, 2017·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Nipha ChaicharoenaudomrungParinya Noisa

Related Concepts

Cordycepin
Adenosine Kinase
Antitubercular Agents
High Pressure Liquid Chromatography Procedure
Liquid Chromatography
Deoxyadenosines
Dose-Response Relationship, Drug
Fungus Drug Sensitivity Tests
Mycobacterium tuberculosis H37Rv
Single Nucleotide Polymorphism

Related Feeds

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.