Predicting Antibiotic Resistance Among Goals of UH Research

Going back in time to compare evolutionary changes in several thousand generations of E. coli, a University of Houston (UH) biologist hopes to one day be able to isolate a bacterial pathogen and predict the likelihood it will become resistant to a particular antibiotic.

A five-year, $967,431 National Science Foundation CAREER Award is allowing associate professor Timothy Cooper and his team to study the causes and consequences of evolvability in bacterial populations. Better understanding the genetic and physiological bases of evolvability is important in vaccine and antibiotic design, as well as in biotechnology. The ultimate goal is to counter it in the former, while exploiting it in the latter.

“Evolvability is when biological populations have the capacity to adapt to changing conditions,” Cooper said. “By studying how generations of bacteria evolve over time, we are learning ways to predict the outcome of the changes and to understand what drives the differences in the way strains of bacteria evolve. We hope this type of evolutionary biology research will impact medical care by contributing to the ability to predict the evolutionary paths of bacterial populations.”

Evolvability plays a crucial role in determining evolutionary winners and losers among the many variants that arise in any bacterial population in that they are either improved or become extinct. Through his research, Cooper wants to gain the ability to predict these winners and losers, because this knowledge gives an element of predictability to evolution. This would predict such things as antibiotic resistance.

Cooper’s evolvability research with the E. coli began two years ago with the first petri dish of this fast-growing bacteria. He says they are lucky, because the experiments are incredibly simple. His team grew the initial bacteria in a petri dish and took a sample to grow in a test tube with fresh media. That process continued day after day with the bacterial populations growing and a sample being taken from each test tube culture. Cooper now has a set of experimental populations that have evolved for more than 7,000 generations.

“This simplicity is deliberate, so that we can track back what has happened to the strain,” Cooper said. “Every 500 generations, which is about every two months, we freeze a sample of each evolving population to create a living fossil record. Because the frozen samples are revivable, we can compare a past population with its future population.”

The comparative analysis of these past and future populations involves genome sequencing. It allows Cooper’s research team, which will include a UH postdoctoral fellow, two graduate students and an undergraduate student, to determine the underlying genetic changes that have occurred, as well as to look at the effect of those changes.

“At this point, we predict an average of about 15 genetic changes to have occurred in each population evolved for the 7,000 generations,” Cooper said. “Though that number may seem small, it’s sufficient enough to increase the bacteria’s growth rate by up to 50 percent.”

Cooper became interested in studying evolvability because it is a long-standing question in evolutionary biology as something that can be modeled in most natural populations, but not measured. While it’s clear from computational models that evolvability can have a major impact on how evolution unfolds, direct study of the phenomenon is required to assess just how big an impact it does have. His group’s experimental system with fast-evolving bacterial populations allows them to design experiments that can look at it directly.

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