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University of Idaho Researchers Aim to Unlock Plasmid Transfer Secrets
In an effort to take the resistance out of antibiotic-resistant bacteria, University of Idaho researchers are getting down to the genetic level to figure out how multi-drug resistance plasmids increase their resistance.
Thanks to a five-year, $1.7 million grant from the National Institutes of Health Eva Top, professor of biology, and Zaid Abdo, assistant professor of mathematics and statistics, will be able to study drug resistance plasmids and the range of bacterial hosts in which they can be supported.
“More and more bacteria are becoming resistant to antibiotics, making it more difficult to treat infections,” says Top. “Plasmids play an important role in this spread of drug resistance, and we want to find out what determines the range of bacterial hosts they can move into. Very little is known about the range of hosts to which plasmids can transfer, and if and how that range can change over time.”
Plasmids are little pieces of DNA within a bacterial cell that jump from bacterium to bacterium. As they spread, they bring genetic information into the new cell and can rapidly increase the number of antibiotics to which bacteria are resistant.
Spurring the research is a growing trend of bacteria that are becoming resistant to antibiotics, like Methicillin-resistant Staphylococcus aureus (MRSA) infections that can become life-threatening. In extreme cases, doctors can run out of antibiotics to treat the infection.
Several factors have been identified as causes of this resistance, such as genetic changes in the chromosomes – which occur slowly over time and one antibiotic at a time. But the factor Top and Abdo are interested in is plasmids.
Top notes these mobile plasmids can confer resistance to 10 or more antibiotics as they move around. While some plasmids have a narrow range of hosts they can transfer to and stably replicate in, broad-host-range plasmids can transfer and replicate in distantly related bacteria – increasing the resistance spectrum. That is where Top's and Abdo's research will focus and provide a foundation for future opportunities to restrict transfer and spread of resistance.
“Plasmids have always been around and have carried antibiotic resistance,” says Eva Top. “But with the high usage of antibiotics, we need to figure out how the plasmids work before we can fight them.” Top, Abdo and their teams of students and researchers will be working to unlock the mystery behind plasmids: why do some plasmids multiply with the bacteria and sometimes the transfer doesn’t take place?
Utilizing undergraduate and graduate biology students and post-doctoral researchers, Top and her team will look at how the plasmids adapt to new bacteria, and how that changes their host range, with the ultimate goal of stopping the spread of resistance to pathogens. She says there will be a lot of lab work involved: growing bacteria, exposing them to plasmids and monitoring the transfer and stability of plasmids in different bacteria.
Abdo and his team of undergraduate and graduate mathematics and statistics students will be building mathematical models to predict long-term change, based on experimental information gathered.
“Mathematical modeling will help us understand underlying causes, make predictions and propose hypotheses about the mechanisms of plasmid host range evolution,” says Abdo.
With five years of research ahead of them, Top, Abdo and their students will be gaining experience that could ultimately lead to saving hundreds of lives. Their NIH-funded research project is titled: ”Plasmids as Vectors of Antibiotic Resistance: The Evolution of Plasmid Host Range.”