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Uncovering new path for drug development.

Biochemical sleuthing has ended a nearly 50-year-old search to find a megamolecule in bacterial cell walls commonly used as a target for antibiotics. Its presence, however, never had been identified in the bacterium responsible for the most commonly reported sexually transmitted disease in the U.S.

For decades researchers had searched for peptidoglycan--a mesh-like polymer that forms the cell wall in diverse bacteria--in the bacterial pathogen Chlamydiae peptidoglycan in hopes of studying its structure and synthesis as a path to drug development against a class of bacteria responsible for one in 10 cases of pneumonia in children, as well as more than 21,000,000 cases of the blindness-causing disease trachoma.

So, when graduate student Erkin Kuru of Indiana University, Bloomington, and a team of researchers that included biologist Yves Brun and chemist Michael S. VanNieuwenhze announced in October 2012 discovery of the first direct and universal approach for labeling peptidoglycan, one of the first places Kuru sought to put his new set of designer chemicals to work was against Chlamydiae.

"People had been trying for about 50 years to identify peptidoglycan in Chlamydiae but had failed even though there was a lot of indirect evidence pointing to its existence," notes Kuru. 'We immediately thought to put our new chemical tagging method using fluorescent D-amino acids to work in an effort to uncover the molecular signature of peptidoglycans in Chlamydiae'.'

The new method uses nontoxic D-amino acidbased fluorescent dyes to label sites where peptidoglycan is synthesized, allowing for fine spatiotemporal tracking of cell wall dynamics. Antibiotics including penicillins, cephalosporins, and vancomycin all target the peptidoglycan assembly site, yet resistance of bacteria to these antibiotics is on the rise.

'The Chlamydia inside the infected cells lit up with green fluorescent peptidoglycan rings in the middle of the red-stained bacterial cells," says Kuru. "It was amazing."

The ability to detect the peptidoglycan will make it possible to solve the mystery of why C. peptidoglycan has remained undetected for so long. Brun concludes, "Obviously, it must be structurally different from the peptidoglycan of most bacteria, and understanding the basis for this difference will help develop strategies to fight this dangerous pathogen."

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Publication:USA Today (Magazine)
Geographic Code:1USA
Date:Apr 1, 2014
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