Study Finds Vitamin C Can Kill Drug-Resistant TB

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Study Finds Vitamin C Can Kill Drug-Resistant TB

May 21, 2013 — (Bronx, NY) — In a striking, unexpected discovery, researchers at Albert Einstein College of Medicine of Yeshiva University have determined that vitamin C kills drug-resistant tuberculosis (TB) bacteria in laboratory culture. The finding suggests that vitamin C added to existing TB drugs could shorten TB therapy, and it highlights a new area for drug design. The study was published today in the online journal Nature Communications.

TB is caused by infection with the bacterium 

M. tuberculosis. 

In 2011, TB sickened some 8.7 million people and took some 1.4 million lives, according to the World Health Organization. Infections that fail to respond to TB drugs are a growing problem: About 650,000 people worldwide now have multi-drug-resistant TB (MDR-TB), 9 percent of whom have extensively drug-resistant TB (XDR-TB).TB is especially acute in low and middle income countries, which account for more than 95 percent of TB-related deaths, according to the 

World Health Organization.

The Einstein discovery arose during research into how TB bacteria become resistant to isoniazid, a potent first-line TB drug. The lead investigator and senior author of the study was William Jacobs, Jr., Ph.D., professor of microbiology & immunology and of genetics at Einstein. Dr. Jacobs is a Howard Hughes Medical Institute investigator and a recently elected member of the National Academy of Sciences.

Dr. Jacobs and his colleagues observed that isoniazid-resistant TB bacteria were deficient in a molecule called mycothiol. “We hypothesized that TB bacteria that can’t make mycothiol might contain more cysteine, an amino acid,” said Dr. Jacobs. “So, we predicted that if we added isoniazid and cysteine to isoniazid-sensitive M. tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture— something totally unexpected.”

The Einstein team suspected that cysteine was helping to kill TB bacteria by acting as a “reducing agent” that triggers the production of reactive oxygen species (sometimes called free radicals), which can damage DNA.

"We predicted that if we added isoniazid and cysteine to isoniazid-sensitive M. tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture— something totally unexpected."

– William Jacobs, Jr., Ph.D.

“To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent— vitamin C,” said Dr. Jacobs. “The combination of isoniazid and vitamin C sterilized the M. tuberculosis culture. We were then amazed to discover that vitamin C by itself not only sterilized the drug-susceptible TB, but also sterilized MDR-TB and XDR-TB strains.”

To justify testing vitamin C in a clinical trial, Dr. Jacobs needed to find the molecular mechanism by which vitamin C exerted its lethal effect. More research produced the answer: Vitamin C induced what is known as a Fenton reaction, causing iron to react with other molecules to create reactive oxygen species that kill the TB bacteria.

- See more at: http://www.einstein.yu.edu/news/releases/907/study-finds-vitamin-c-can-kill-drug-resistant-tb/#sthash.ww7RqFgU.dpuf

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Bill Jacobs Elected to the National Academy of Sciences

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Bill Jacobs Elected to the National Academy of Sciences

 May 1, 2013 – (BRONX, NY) – Two faculty members at Albert Einstein College of Medicine of Yeshiva University have been elected to the National Academy of Sciences. Robert Singer, Ph.D., and William Jacobs, Jr., Ph.D., were among the select scientists who will be inducted into the Washington-based organization at a ceremony in April 2014.

William Jacobs, Jr., Ph.D., Robert Singer, Ph.D.“Bill Jacobs’ and Rob Singer’s election to the National Academy of Sciences is a richly deserved honor that reflects the extraordinary discoveries each has made,” said Allen M. Spiegel, M.D., the Marilyn and Stanley M. Katz Dean at Einstein. “We are proud to have scientists of their caliber on our faculty.”

Dr. Singer, professor and co-chair of anatomy and structural biology, is a world leader in developing novel methods for investigating the most fundamental processes in living cells: how the message encoded in the DNA of genes is transcribed into RNA and then translated into proteins. His lab developed the FISH (fluorescence in situ hybridization), a widely used technology to visualize and isolate individual molecules of RNA in a single cell, and was the first to establish that each RNA strand has a non-coding region that determines it’s “zip code” in the cell. Dr. Singer is also co-director of the Gruss Lipper Biophotonics Center and of the Integrated Imaging Program and holds the Harold and Muriel Block Chair in Anatomy and Structural Biology.

Dr. Jacobs, professor of microbiology & immunology, is pioneering the use of molecular genetics to control tuberculosis (TB), which kills nearly two million people a year. His research is investigating the genes that make Mycobacterium tuberculosis (MTB)—the bacterium that causes TB—virulent, identifying new drug targets and engineering weakened strains that can be used as live vaccines. Dr. Jacobs was the first scientist to introduce foreign DNA into MTB, a technique now regularly used by TB investigators around the world. He is also professor of genetics and a Howard Hughes Medical Institute (HHMI) investigator.

“Bill Jacobs' and Rob Singer’s election to the National Academy of Sciences is a richly deserved honor that reflects the extraordinary discoveries each has made. We are proud to have scientists of their caliber on our faculty.”

-- Dean Allen M. Spiegel, M.D.

Drs. Singer and Jacobs were two of 84 new members and 21 foreign associates from 14 countries who were elected to the academy in recognition of their distinguished and continuing achievements in original research. Those elected yesterday bring the total number of active members to 2,179 and the total number of foreign associates to 437. Foreign associates are nonvoting members of the Academy, with citizenship outside the United States.

The National Academy of Sciences is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and—with the National Academy of Engineering, Institute of Medicine, and National Research Council—provides science, technology, and health policy advice to the federal government and other organizations.

- See more at: http://www.einstein.yu.edu/news/releases/895/faculty-members-at-albert-einstein-college-of-medicine-elected-to-national-academy-of-sciences/#sthash.lk9gP1ds.dpuf

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