Navigation Links
Promising class of antibiotics discovered for treatment of drug-resistant tuberculosis
Date:1/27/2014

St. Jude Children's Research Hospital scientists have discovered a promising new class of antibiotics that could aid efforts to overcome drug-resistance in tuberculosis (TB), a global killer. The drugs increased survival of mice infected with TB and were effective against drug-resistant strains of TB. St. Jude led the international research effort, results of which appear in the current issue of the journal Nature Medicine.

The antibiotics, called spectinamides, were created by changing the chemical structure of an existing antibiotic, spectinomycin, which does not work against TB.

In multiple trials of mice with both active and chronic TB infections, researchers report that one version of the new drugan analog known as 1599was as good as or better than current TB drugs at reducing levels of the bacteria in the lungs of mice. In addition, 1599 caused no serious side effects.

"This study demonstrates how classic antibiotics derived from natural products can be redesigned to create semi-synthetic compounds to overcome drug resistance," said corresponding author Richard Lee, Ph.D., a member of the St. Jude Department of Chemical Biology and Therapeutics. "I hope the result will be drugs that are more effective against tuberculosis and offer a faster route to a cure with fewer side effects."

TB remains a leading cause of global illness and death. The latest data from the World Health Organization estimates that TB kills 1.3 million persons annually and sickens 8.6 million worldwide. Current treatment requires months of multi-drug therapy to eradicate the slow-growing bacterium, which can lie dormant for years without causing symptoms and results in hard to treat chronic or latent infections. The rise of multi-drug resistant TB, including strains reportedly resistant to all available medications, has further complicated treatment.

This new class of antibiotics works against TB by disrupting the function of a part of the cell known as the ribosome, which is responsible for protein synthesis. To do that, the spectinamides bind to a particular site on ribosomes that is not shared by other TB drugs. That allows the drug to be used in combination with other medications.

For this study, researchers used an approach called structure-based design to re-engineer how spectinomycin binds to the ribosome. To guide their design efforts, scientists used a 3-D model that provided an atomic-level view of spectinomycin bound to the tuberculosis ribosome. The study reinforces the potential of structure-based design as a tool for designing other new agents to block mechanisms TB and other bacteria use to resist current antibiotics, Lee said.

The research reports on the first 20 of the more than 120 spectinomycin derivatives that have resulted from the effort. The list includes 1599 and two other analogs tested against TB in mice.

The three analogs not only bound the ribosome tightly, but they were more successful at avoiding a TB resistance mechanism called efflux. The TB bacteria use efflux pumps as a strategy to remove drugs and other threats from the cell before they can work against the bacteria. Efflux pumps, however, did not protect TB against spectinamides.

The drugs were also effective against multi-drug-resistant strains of TB growing in the laboratory. The strains had been isolated from patients with the disease.

Researchers also found no evidence that 1599 or the two other analogs tested interfered with normal functioning of human cells. Preliminary safety testing on cells grown in the laboratory showed the drugs were not toxic to mammalian cells because they only inhibit the bacterial ribosomes and not mammalian ribosomes.

Work is underway now in mice combining 1599 with new or existing TB drugs. The goal is to identify multi-drug therapy to try in a clinical trial of patients with drug-resistant TB.


'/>"/>

Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert  

Related biology news :

1. First complete full genetic map of promising energy crop
2. Scripps Research Institute scientists find promising vaccine targets on hepatitis C virus
3. Promising developments in early diagnosis and treatment of mesothelioma
4. Ultrasensitive biosensor promising for medical diagnostics
5. UH Case Medical Center, CardioKinetix reveal promising data for treatment for heart failure
6. 22 of Americas most promising scientists selected as Pew Biomedical Scholars
7. American Health Assistance Foundation announces grants to advance promising vision research
8. Space research institute awards funding to promising medical products
9. Promising new drug target for inflammatory lung diseases
10. Berkeley Lab scientists help develop promising therapy for Huntingtons disease
11. Stem cells + nanofibers = Promising nerve research
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Promising class of antibiotics discovered for treatment of drug-resistant tuberculosis
(Date:2/27/2017)... , Feb. 27, 2017   Strategic Cyber Ventures ... it has led a $3.5 million investment in  Polarity ... Strategic Cyber Ventures is DC based and is led ... Hank Thomas . Ron Gula , also a ... also participated in this series A round of funding. ...
(Date:2/21/2017)... PORTLAND, Ore. , Feb. 22, 2017 ... Family of Companies (Avamere Health Services, Infinity Rehab, Signature ... research study that will apply the power of IBM ... living and health centers. By analyzing data streaming from ... insights into physical and environmental conditions, and obtain deeper ...
(Date:2/13/2017)... Feb. 13, 2017  RSA Conference -- RSA, a ... is designed to enhance fraud detection and investigation ... the RSA Fraud & Risk Intelligence Suite. The ... leverage additional insights from internal and external sources ... protect their customers from targeted cybercrime attacks. ...
Breaking Biology News(10 mins):
(Date:3/22/2017)... LEXINGTON, Mass. , March 22, 2017   ... collections, today announced that Doctors Pathology Service ... mid-Atlantic region of the United States ... the Delaware Health Information Network (DHIN) to ... researchers. The novel program, announced in ...
(Date:3/22/2017)... TORONTO , March 22, 2017 /PRNewswire/ - ... Therapeutics (the "Company" or "Propellon"), a start-up created ... WDR5-targeted anti-cancer therapeutics. FACIT,s investment, combined with non-dilutive ... lead program. The seed funding enables Propellon to ... position the Company for financing and/or entering a ...
(Date:3/22/2017)... ... ... Premier executive recruitment firm, Slone Partners, is proud to have been named a Top ... Hunt Scanlon Media is one of the most respected life science publications in the ... sector. , “It is a great honor for Slone Partners to be part of ...
(Date:3/22/2017)... , ... March 21, 2017 , ... Benchworks ... Chief Executive Officer Forum on March 23-24 in San Diego. The event is ... and diagnostic industries. , Benchworks Vice President Christian Meyer will also participate in ...
Breaking Biology Technology: