Featured Research

from universities, journals, and other organizations

Promising class of antibiotics discovered for treatment of drug-resistant tuberculosis

Date:
January 27, 2014
Source:
St. Jude Children's Research Hospital
Summary:
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 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.

Related Articles


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 drug -- an analog known as 1599 -- was 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.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Richard E Lee, Julian G Hurdle, Jiuyu Liu, David F Bruhn, Tanja Matt, Michael S Scherman, Pavan K Vaddady, Zhong Zheng, Jianjun Qi, Rashid Akbergenov, Sourav Das, Dora B Madhura, Chetan Rathi, Ashit Trivedi, Cristina Villellas, Robin B Lee, Rakesh, Samanthi L Waidyarachchi, Dianqing Sun, Michael R McNeil, Jose A Ainsa, Helena I Boshoff, Mercedes Gonzalez-Juarrero, Bernd Meibohm, Erik C Bφttger, Anne J Lenaerts. Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux. Nature Medicine, 2014; DOI: 10.1038/nm.3458

Cite This Page:

St. Jude Children's Research Hospital. "Promising class of antibiotics discovered for treatment of drug-resistant tuberculosis." ScienceDaily. ScienceDaily, 27 January 2014. <www.sciencedaily.com/releases/2014/01/140127141902.htm>.
St. Jude Children's Research Hospital. (2014, January 27). Promising class of antibiotics discovered for treatment of drug-resistant tuberculosis. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2014/01/140127141902.htm
St. Jude Children's Research Hospital. "Promising class of antibiotics discovered for treatment of drug-resistant tuberculosis." ScienceDaily. www.sciencedaily.com/releases/2014/01/140127141902.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) — An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins