Life Science Hour Seminar Series

Name:Eva Top
Title:Compensatory mutations pre-adapt bacteria to diverse antibiotic resistance plasmids
Date:Friday, 2 March 2018
Location:Murie Life Science Bldg, Murie Auditorium.


Horizontal gene transfer mediated by broad-host-range plasmids is an important mechanism of antibiotic resistance spread. While not all bacteria maintain plasmids equally well, plasmid persistence can improve over time. Research on experimental evolution of bacteria with multi-drug resistance plasmids has shown that single mutations in either the chromosome, the plasmid or both can improve the plasmid’s persistence in the absence of antibiotics, and thus promote the spread of antibiotic resistance to human pathogens. However, general evolutionary mechanisms have not yet emerged. Our goal was to identify these mechanisms, and to assess if adaptation to one plasmid pre-adapts the bacteria to other plasmids. We experimentally evolved Pseudomonas sp. H2 containing multi-drug resistance plasmid RP4, determined plasmid persistence and cost using a joint experimental-modeling approach, resequenced evolved clones, and reconstructed key mutations. Plasmid persistence improved in fewer than 600 generations because the fitness cost turned into a benefit. Improved retention of naive plasmids indicated that the host evolved towards increased plasmid permissiveness. Key chromosomal mutations affected two accessory helicases and the RNA polymerase β-subunit. Our and other findings suggest that poor persistence of an antibiotic resistance plasmid can be caused by a high cost involving helicase-plasmid interactions that can be rapidly ameliorated.

About the Speaker:

Eva Top is Professor of Biology at the University of Idaho. She received her Masters and Ph.D. degrees from the Ghent University in Belgium in biological engineering and microbial ecology. Her research is currently focused on the ecology and evolution of multi-drug resistance (MDR) plasmids in bacteria. Since rapid spread of MDR to human pathogens threatens the treatment of infectious diseases, novel therapies are needed that limit the spread of new resistance genes. However, the factors that determine successful transfer and persistence of MDR plasmids are still poorly understood. Her main research questions focus on the evolutionary mechanisms and dynamics of plasmid-bacteria co-evolution. She is also interested in the diversity and evolutionary history of natural MDR plasmids, and studies the effects of spreading dairy manure on the abundance and diversity of MDR plasmid reservoirs in soils.

Top is the Director of the Bioinformatics and Computational Biology graduate program at the University of Idaho (BCB). She is also the Secretary for the International Society for Plasmid Biology and other Mobile Genetic Elements, and is co-organizing the “Plasmid Biology 2018” conference in Seattle this summer. In 2017 she co-chaired the Gordon Research Conference on Microbial Population Biology.

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