Harvill Group Awarded New Grant to Study Transmission

Harvill Group Awarded New Grant to Study Transmission

By: Blue Harvill

Dr. Harvill and lab are studying the mouse-model system of infectious disease transmission in their most recent grant proposal. With collaborators Drs. Bar Peled and Dewan, Dr. Harvill has received funding from the National Institutes of Health for $412,000 to study Bordetella bronchiseptica virulence in mice as an important experimental model of disease transmission.

The goal is to find specific factors involved in transmission, “transmission factors”, through observation in the experimental model they have established. Future interventions may then use these transmission factors as targets.

There is currently a vaccine in use to prevent whooping cough, but it has some major flaws. The vaccine prevents illness and symptoms of whooping cough. Yet, vaccinated individuals can still be subject to colonization by Bordetella pertussis, and can transmit it to others. “Getting vaccinated prevents disease, but does not appear to provide much herd immunity in this case, because the bacteria is still relatively common,” Dr. Harvill elaborates.

B. pertussis and B. bronchiseptica share conserved genes related to transmission. B. bronchiseptica findings may inform future preventions for B. pertussis.

The grant funds new work seeking to identify exactly which genes transmission requires. Isolating genes of the virulence factor (transmission exopolysaccharide) will aid in determining functions. These complex sugars that bacteria secrete into a capsule around their cell body have unknown transmission-related properties. Dr. Harvill explains, “It takes a lot of energy for bacteria to secrete these large sugars, so they must be doing something important.”

Gene expression can be observed at every stage of the transmission process. In the mouse model this includes colonization, shedding, and survival in the environment.

The study seeks to determine the complete structure and properties of the transmission factors. Unsuccessful mutants will enable scientists to identify bacterial transmission requirements. This study will discover the locations and properties of expressed genes. Dr. Harvill also hopes to find out which genes encode cellular and transmission activities.

Expectations of the research include to find sites of vulnerability for the bacteria's metabolism. These will be targets for future interventions. He also hopes to find applications for more pathogens from this study.

This grant allows the Harvill lab to show the importance of experimental models. The study will be a stepping stone for future work on new and more effective vaccines. Dr. Harvill proposes

that, “arguably, transmission between hosts is the most important thing that infectious diseases have to do, but we know very little about the process. Learning how infectious diseases spread can help us learn how to better control them.”

Finally, this study can also inform a better understanding of all disease spread. The implications are not limited to B. bronchiseptica. Experimental modeling provides much better detail, down to the molecular level than mathematical models or clinical observation.

A more detailed understanding of infectious disease may be the key to disease prevention.

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