New study gains significantly better understanding of antibiotic resistance, leading to new antibiotics development

According to recent statistics published in the Nature (cited by Thomas A. Steitz, a Howard Hughes Medical Institute investigator at Yale University), hospitals in the United States see about two million cases of antibiotic-resistant infections each year; 90,000 patients die annually from such infections.

Antibiotic resistance is a big problem for renal transplant recipients and is a big cause of concern in way of long term survival and well being.

Ribosomal mutation dubbed L22 confers resistance to macrolides such as erythromycin. Paradoxically this mutation confers resistance, even though the antibiotic still binds to the mutant ribosome.

The new structural data indicate that the L22 mutation increases the size of a “tunnel” in the ribosome, through which the growing peptide chain moves during synthesis. This tunnel is normally blocked by macrolide antibiotics. In the mutant form, the tunnel widens, which may explain why macrolide antibiotics are no longer effective.

The research was led by Thomas A. Steitz, a Howard Hughes Medical Institute investigator at Yale University, and Peter B. Moore, a professor of chemistry at Yale, published its findings in the April 22, 2005, issue of the journal Cell.

According to Steitz, insights about the ribosomal origins of antibiotic resistance are already being applied to the development of new antibiotics. One company leading the way is Rib-X Pharmaceuticals, which was founded by Steitz and colleagues at Yale.

“About half of current antibiotics target the ribosome, and most of them target the large subunit,” he said. “So, such advances have the potential for significant clinical impact.

Their core idea is to combine antibiotics. So if the resistance develops due to mutation in one targeting site, the other site still can be binded to and confers protection. It is similar to multi-drug therapy of AIDS. However in this case, unlike AIDS therapy, the multiple binding sites are linked in one molecule.

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