Monday, August 6, 2012

Trana Discovery Finds Common tRNA Target for LRTI Antibiotic Development

CED Member Trana Discovery, Inc. today announced the identification of a target for the development of new antibiotics for community-acquired lower respiratory tract infections (CA-LRTI). The target, the anticodon stem loop (ASL) found in transfer RNA used by bacteria for replication, is common in the majority of the bacteria that cause CA-LRTI but not in the most beneficial bacteria in the gastrointestinal tract.  This discovery will enable Trana to develop an assay to identify compounds that could treat LRTIs without the side effects associated with antibiotics that kill the beneficial bacteria normally found in the gastrointestinal tract.  The target represents a major advance for the discovery of novel antibacterial agents for CA-LRTI.

Lower respiratory tract infections are a significant cause of mortality and morbidity, particularly among the very young and very old.  A challenge in managing these infections is selecting empiric therapy with activity against the most likely bacteria that cause rapid disease progression.  Antibiotics effective against one of these bacteria may not be effective against another.  As a result, physicians frequently initiate treatment with broad-spectrum antibiotics or combination therapy.  While effective, these antibiotics may also destroy some of the beneficial bacteria in the gastrointestinal tract, causing side effects like diarrhea, development of drug-resistant bacterial strains in the colon, and C. difficile infection.

Using advanced identification methods, scientists at Trana discovered the common tRNA target associated with eight bacterial species known to cause CA-LRTI, including Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, Streptococcus agalactiae (Group B), Streptococcus pneumoniae and Streptococcus pyogenes (Group A).

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 antibacterial drugs, including those for treatment of LRTIs. In addition, the target ASL is not found in most of the essential bacteria of the GI tract; therefore, GI side effects are not anticipated to be a major issue with these agents.

"A majority of bacteria that cause lower respiratory tract infections share a common piece of tRNA,” said Mike Ossi, MD, Chief Scientific Officer of Trana Discovery. "Our tRNA-based drug discovery technology can speed the discovery and development of novel compounds that help treat these infections and ultimately save more lives."

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 CA-LRTIs. 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.

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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