A team of scientists in Argentina and Mexico identified mutations that increased the efficiency of a bacterial enzyme that renders penicillin and cephalosporin antibiotics useless. The results could lead to more effective enzyme inhibitors by giving drug designers a sneak peek at the next generation of resistance.
Alejandro Vila, a Howard Hughes Medical Institute international research scholar, and colleagues at the University of Rosario's Institute of Molecular and Cellular Biology in Argentina and at the Biotechnology Institute of the National Autonomous University of Mexico report their findings in the early online edition of the Proceedings of the National Academy of Sciences the week of September 19, 2005.
Staying one step ahead of resistance with new antibiotics and treatments for infections is a huge challenge because bacteria evolve quickly to evade them. When the scientists introduced random mutations into the gene for a bacterial resistance enzyme and grew the bacteria on increasing concentrations of antibiotics, it took only a few days of test tube evolution to increase drug resistance. Eventually, they found four mutations in the evolved enzyme that allowed the bacteria to survive on a drug dose 64 times higher than the dose that kills bacteria hosting the un-evolved enzyme.
"We were mimicking what is going on in the doctor's clinic -- putting selection pressure on the enzyme by giving higher doses of antibiotic," said Vila. "The only ones to survive will be those that have an enzyme that can work more efficiently."