TB-drugome provides new targets for anti-tuberculosis drug discovery

Nov 08, 2010

Researchers at the University of California, San Diego School of Medicine and the University of Leeds have linked hundreds of federally approved drugs to more than 1,000 proteins in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), opening new avenues to repurpose these drugs to treat TB.

The study was published Nov. 4 in .

"Tuberculosis is currently one of the most widely spread infectious diseases, with an estimated one-third of the world's population infected and between one and two million people dying each year from the disease," said Philip Bourne, PhD, professor of pharmacology at UCSD's Skaggs School of Pharmacy and Pharmaceutical Sciences. "The continuing emergence of M. tuberculosis strains resistant to all existing, affordable drug treatments requires the development of novel, effective and inexpensive drugs.

The newly developed TB-drugome may help that effort, Bourne said, by identifying new M. tuberculosis protein targets that can be perturbed by a variety of existing drugs prescribed for other purposes.

Sarah Kinnings at the University of Leeds and a team of scientists at UC San Diego, led by Bourne (who is also associate director of the RCSB Protein Data Bank) and research scientist Lei Xie, PhD, used a novel computational strategy to investigate whether any existing drugs were able to bind to any of the approximately 40 percent of proteins in the M. tuberculosis proteome with decipherable three-dimensional structures.

The researchers not only discovered that approximately one-third of the drugs examined may have the potential to be repurposed to treat tuberculosis, but also that many currently unexploited M. tuberculosis proteins could serve as novel anti-tubercular targets. This finding led the investigators to construct a complex network of drug-target interactions – a TB-drugome available to all scientists.

While this new computational, high-throughput process of is promising, Xie cautioned that "only experimentation can validate the most promising drug-target combinations, and there will be many failures along the way."

Kinnings added that any drugs subsequently confirmed to bind to M. proteins may need to be modified to increase their ability to penetrate the bacterial cell membrane, reduce their required dosage, and improve other pharmacological properties. The screening of a large collection of analogs to known drugs will be the next step towards anti-tuberculosis drug discovery.

Explore further: Overwhelmed west Africa ramps up Ebola response

add to favorites email to friend print save as pdf

Related Stories

Drug-resistant tuberculosis rife in China

Dec 11, 2008

Levels of drug-resistant tuberculosis (TB) in China are nearly twice the global average. Nationwide research published in the open access journal BMC Infectious Diseases has shown that almost 10% of Chinese TB cases are re ...

HIV/AIDS linked to drug resistant TB

Nov 16, 2006

U.S. scientists say a highly drug-resistant form of tuberculosis has been linked to HIV/AIDS in a study conducted in rural South Africa.

Recommended for you

Overwhelmed west Africa ramps up Ebola response

7 hours ago

West Africa intensified its response to the deadly Ebola epidemic on Sunday, with Sierra Leone uncovering scores of dead bodies during a 72-hour shutdown and Liberia announcing hundreds of new hospital beds.

Sierra Leone reaches final day of Ebola lockdown

10 hours ago

Frustrated residents complained of food shortages in some neighborhoods of Sierra Leone's capital on Sunday as the country reached the third and final day of a sweeping, unprecedented lockdown designed to ...

Sierra Leone faces criticism over Ebola shutdown

Sep 20, 2014

Sierra Leone began the second day of a 72-hour nationwide shutdown aimed at containing the spread of the deadly Ebola virus on Saturday amid criticism that the action was a poorly planned publicity stunt.

Presence of peers ups health workers' hand hygiene

Sep 19, 2014

(HealthDay)—The presence of other health care workers improves hand hygiene adherence, according to a study published in the October issue of Infection Control and Hospital Epidemiology.

User comments : 0