Biochemical sleuthing by an Indiana University graduate student has ended a nearly 50-year-old search to find a megamolecule in bacterial cell walls commonly used as a target for antibiotics, but whose presence had never been identified in the bacterium responsible for the most commonly reported sexually transmitted disease in the United States.
For decades researchers had searched for peptidoglycan -- a mesh-like polymer that forms the cell wall in diverse bacteria -- in the bacterial pathogen Chlamydiae in hopes of studying the megamolecule's structure and synthesis as a path to drug development against a class of bacteria responsible for 1 in 10 cases of pneumonia in children and over 21 million cases of the blindness-causing disease trachoma.
So when IU graduate student Erkin Kuru and a team of researchers that included IU biologist Yves Brun and chemist Michael S. VanNieuwenhze announced discovery in October 2012 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," said Kuru, a native of Istanbul, Turkey, doing graduate studies in the IU Bloomington College of Arts and Sciences' Interdisciplinary Biochemistry Program. "We immediately thought to put our new chemical tagging method using fluorescent D-amino acids (FDAAs) to work in an effort to uncover the molecular signature of peptidoglycans in Chlamydiae."
The new method uses nontoxic D-amino acid-based fluorescent dyes to label sites where peptidoglycan is synthesized, allowing for fine spatiotemporal tracking of cell wall dynamics. Antibiotics including the penicillins, the cephalosporins and vancomycin all target the peptidoglycan assembly site, yet resistance of bac
|Contact: Stephen Chaplin|