Brian Ingalls

Decreasing antibiotic resistance in bacteria

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.

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