Monday, September 17, 2012

Trana Discovery Finds Common tRNA Target for Gram-negative Antibiotic Development

CED Member Trana Discovery, Inc., a Cary-based drug discovery technology company, today announced the identification of a target for the development of new antibiotics for infections caused by hospital-acquired Gram-negative bacteria. The target, the anticodon stem loop (ASL) found in transfer RNA used by bacteria for replication, is common in four of the most deadly bacteria that cause serious hospital-acquired infections but not in many of the most beneficial bacteria in the gastrointestinal tract.  This discovery will enable Trana to develop an assay to identify compounds that could treat Gram-negative infections without the side effects associated with antibiotics that also eradicate many of the beneficial bacteria normally found in the gastrointestinal tract.  The target represents a major advance for the discovery of novel antibacterial agents to combat Gram-negative infections.

In the hospital environment and particularly in the ICU, infections caused by Gram-negative bacteria result in significant morbidity and mortality. Because of their cell wall structure and their increasing ability to produce new resistance mechanisms, physicians treating these infections are forced to use older antibiotics that have unwanted side effects or to initiate broad spectrum or combination therapy that can result in antibiotic associated diarrhea, further resistance pressure and C. difficile infection.

Using advanced identification methods, scientists at Trana discovered the common tRNA target associated with four bacterial species known to cause hospital-acquired Gram-negative infections, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii.

Trana technology discovers antimicrobial compounds that inhibit transfer RNA (tRNA) specific to a targeted pathogen. Proper tRNA-mRNA binding associated with the anticodon stem loop (ASL) in the tRNA molecule is essential for bacterial protein synthesis and pathogen replication. Compounds that can disrupt this binding have the potential to be developed into new antibacterial drugs, including those for treatment of Gram-negative bacteria.

The Centers for Disease Control and Prevention estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to 99,000 deaths in the U.S. each year. In Europe, hospital-acquired Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year.

"The most troublesome Gram-negative bacteria share a common piece of tRNA that can be exploited in the development of new antibiotics that ultimately can save lives.” said Mike Ossi, MD, Chief Scientific Officer of Trana Discovery.

Trana will be working to develop an assay that can screen thousands of compounds at a time for discovery of potential antibiotics for treatment of Gram-negative bacterial infections. The proprietary technology can also be applied to other infectious diseases, including chronic diseases such as HIV, bacterial diseases caused by multi-drug resistant strains, and resistant fungal diseases. In addition, recent discoveries of unique tRNAs common to a group of organisms commonly associated with community-acquired lower respiratory tract infections (CA-LRTI) will enable Trana to develop an assay to identify compounds that could treat LRTIs while minimizing or eliminating antibiotic-associated GI side effects.

Trana has developed assays that are capable of identifying compounds that interfere with the use of tRNA for S. aureus and HIV, the cause of AIDS.

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