IU researchers' findings aid in fight against E Coli bacteria

A recent study conducted on spontaneous mutations in microorganisms by IU researchers Patricia Foster and Jill Layton may help the effectiveness of antibiotics.\nTheir study indicates that although spontaneous mutations in microorganisms under adverse circumstances are common, the rise in adaptive mutations in Escherichia Coli, a common bacterium found in molecular biology laboratories, is a direct response to a lack of nutrients.\nAt times, mutations in bacteria can cause a resistance to antibiotics. The newfound research provides scientists with more knowledge about mutations in bacteria, which could benefit the effectiveness of drugs in the future.\nUnder favorable circumstances, E Coli reproduces by copying itself every 20 minutes through a process called binary fission. The accuracy associated with DNA replication is especially important because the genes within contain the instructions for bacterium growth and development.\nAmong a variety of enzymes called DNA polymerases responsible for copying DNA molecules, Polymerase I (Pol I), Pol II and Pol III boast remarkably high accuracy, producing exact duplicates with a very little chance of error. In contrast, Pol IV and Pol V lack such ability and may create a structural modification in the DNA, which results in a genetic mutation.\n"The classic idea is that mutations are caused by molecules interacting with the nucleotides or by X-ray and gamma radiation, which cause changes in the DNA," said Albert Ruesink, a professor of biology. "This is essentially a random process and there is no relation between the stimulus and what the nature of the mutation might be."\nThe research shows that when E Coli lacks food, the bacterium responds by changing its metabolic pathways. \n"Something runs out -- in our case, it's their sugar source," Foster said. "The bacteria induce an enzyme that increases the mutations, and the idea is that if they had the right mutation, they would be able to find another source of nutrients." \nThe enzyme, identified in the research as sigma-38, gives rise to Pol IV molecules in quantities as many as four times the usual number. Since Pol IV is highly error-prone, its increased production almost guarantees a mutation of some type. \nSuch environmentally-induced mutation produces two possible results. If the desired improvement is achieved, the bacterium survives and passes its genes onto the next generation equipped with the same favorable DNA revision, thus increasing its chance of survival. Otherwise, the bacterium becomes something useless -- which is what usually happens -- and the complications destroy the organism.\nIn a larger evolutionary perspective, induced mutations grant natural selection more options. \n"In order to evolve, there has to be a pool of variation for the natural selection to occur," Foster said. "This is a way bacteria can increase its variation."\nUnderstanding bacterial mutations is of great interest in the medical field in combating mutation-ready microorganisms. Certain strains of infectious bacteria tend to resist antibiotics because of their spontaneous mutations that render the drugs useless. \n"Think of it as a light switch," Layton said. "If we can figure out a way to shut the enzyme off, it can stall or slow down the process by which these bacteria mutate and become resistant to antibiotics."\nControl over microorganisms presents applications that might prove extremely beneficial in the future. \n"You could, for example, ask a strain of bacteria to utilize toxic chemicals," Foster suggested. "Maybe they won't be so good at it, but we could induce them to mutate so they would get better."\nThe current development is the result of three years of effort, and the research is still an ongoing process. \n"This is just a place on the way," Foster said. "The first step, if you will."\n-- Contact staff writer Jun Chung at juchung@indiana.edu.