Researchers at the University of Idaho, led by professor Eva Top, discovered two genes that aid a bacteria’s ability to hold onto genetic material coding for antibiotic resistance.
“Bacteria become resistant in two major ways — mutation, and what we study, plasmids,” Top said.
Plasmids are genetic material that bacteria exchange with each other without reproduction, allowing the adoption of traits critical to a bacteria’s survival in a process much faster than inheritance, Top said.
“Nobody really knows where they come from,” Top said. “Some can even transfer between species.”
Top, a researcher at UI’s Institute for Bioinformatics and Evolutionary Studies, and researchers from the University of Florida, the University of Washington and Point Loma Nazarene University received $1.7 million in grant funding from the National Institutes of Health to study the genetics behind plasmids. UI’s Wesley Loftie-Eaton, Jack Milstein, Samuel Hunter, Kelsie Bashford and Kieran Dong worked on the project.
The team identified two genes that help a harmless variant of Pseudomonas bacteria hold onto plasmids coding for antibiotic resistance.
“For a while we were in the age of antibiotics and we thought we were winning,” Top said. “Now resistance is appearing.”
Antibiotics rendered obsolete by evolution may still have use, however, as plasmids often leave a species as quickly as they appear. Top said study of the mechanisms which allow bacteria to hold onto plasmids could lead to a method of blocking those plasmids.
Top said her researchers selected for antibiotic resistance over many generations by exposing the bacteria to the drug. She said DNA sequencing to compare the resistant generations to the previous was done at the Integrated Research and Innovation Center.
Researchers usually identify only one gene for traits like this, Top said, but her team found two that appear to work together. She said one codes for retention of the specific plasmid, while the other codes for retention of plasmids in general.
With the original grant completed, Top said she is requesting additional funds for further research on the subject. Top said her first attempt to obtain the nearly $2 million funding she needs was rejected, but another proposal is on the way.
She said future research will look into the mechanisms behind each gene — how bacteria hold onto specific plasmids and how they hold onto plasmids in general — with the hope of gaining insight into how to block the mechanisms, allowing obsolete antibiotics to work again.
Top said solutions could take many forms, including developing similar plasmids to trick the bacteria and take the place of resistance plasmids. Another solution, she said, would be to find a molecule that physically blocks the plasmid from being absorbed.
The research could lead to solutions to many species’ antibiotic resistance, including a harmful species of what Top’s team studied, Pseudomonas aeruginosa.
The team’s full paper, “Compensatory mutations improve general permissiveness to antibiotic resistance plasmids,” is published in Nature Ecology & Evolution, an online scientific research journal.
Nishant Mohan may be reached at [email protected] or on Twitter @NishantRMohan