Centre for Bioengineering and Biotechnology
University of Waterloo, East Campus 4, Room 2001
200 University Avenue West
Waterloo , Ontario, N2L 3G1 Canada
519-888-4567 Ext 32732
By Nicolas Huguet, CBB Biographer
August 6, 2015
Antibiotic resistant bacteria are a growing health concern. CBB member Prof. Brian Ingalls is using his background in Applied Mathematics and Synthetic Biology to tackle this problem.
Antibiotic resistance is usually conferred by a plasmid -- a DNA molecule that resides in a cell but is not part of the cell’s genome. Prof. Ingalls and his students are addressing the question of how these plasmids can be removed from a population of cells, rendering them antibiotic sensitive. They are pursuing a two-step solution.
One step is plasmid displacement, in which the target (antibiotic resistance) plasmid can be displaced from a cell by a competing plasmid that does not carry antibiotic resistance genes. Prof. Ingalls’ group is taking advantage of a natural feature of plasmid biology that causes some pairs of plasmids to be incompatible, in the sense that when they share a host cell, one plasmid eventually displaces the other. They have engineered plasmids that will compete with antibiotic resistance plasmids in this way, and are currently carrying out proof-of-concept experiments in the lab.
The second step is delivery of the engineered “competitor” plasmid to a bacterial population of interest. Prof. Ingalls’ group is investigating delivery by conjugation, which is a natural process by which genetic material is passed between bacterial cells. Conjugation will not only allow for an initial “sender” population to deliver the engineered “competitor” plasmid to an antibiotic resistant population of pathogens, but will also result in the engineered plasmid being passed from cell to cell within the target population.
Once the bacteria are free of the target plasmid, they can then be treated effectively using antibiotics. Prof. Ingalls is planning to target antibiotic resistance genes in environmental populations such as in hospitals or in waste water treatment plants, where significant gene transfer occurs. By targeting these environments, Prof. Ingalls work could potentially curb the spread of antibiotic resistance, thereby improving public health.
The University of Waterloo acknowledges that much of our work takes place on the traditional territory of the Neutral, Anishinaabeg and Haudenosaunee peoples. Our main campus is situated on the Haldimand Tract, the land granted to the Six Nations that includes six miles on each side of the Grand River. Our active work toward reconciliation takes place across our campuses through research, learning, teaching, and community building, and is centralized within our Office of Indigenous Relations.