Team maps genes of 10th costly animal pathogen

PULLMAN, Wash. – A team of scientists at Washington State University recently sequenced and published the genome of their 10th animal disease microorganism.

 

Diseases caused by such agents cost animal industries and subsistence owners worldwide billions of dollars a year. Unraveling the genetic code helps researchers better understand how to combat these pathogens.

 

Kelly Brayton. (Photo by Henry Moore Jr., BCU/WSU)

“My greatest pride is in knowing that I contributed to the body of knowledge that will likely lead to prevention and control for these diseases,” said Kelly Brayton, associate professor and the Caroline Engle Faculty Fellow in the Department of Veterinary Microbiology and Pathology and the Paul G. Allen School for Global Animal Health.

 

The list of disease agents Brayton has pursued is a rogue’s gallery of dangerous microorganisms. They typically lack common names, and most people – except livestock owners – have never heard of them.

 

Brayton has unraveled the genomes for several strains of Anaplasma marginale, the most prevalent, tick-borne livestock disease agent worldwide. She has worked out the genomics of Babesia bovis, an intracellular protozoan parasite that causes disease in cattle; sequenced the genome of Ehrlichia ruminantum, which causes African heartwater disease in ruminants; and compared the genetic makeup of ovine herpesvirus 2 from domestic sheep to that from cows.

The most recently completed genome is that of Theileria equi, an intracellular protozoan parasite that causes piroplasmosis in horses, mules, donkeys and zebras. An intensive campaign eradicated this pathogen from the United States in the 1960s at a cost of $12 million, and until recently the U.S. was considered free of the disease agent. However, three years ago horses in Texas tested positive and, subsequently, positive horses have been detected in 16 states.

 

As with many of the pathogens that Brayton targets, T. equi can establish a lifelong persistent infection – once an animal is infected it is unable to clear the infection with an immune response.

“There are several mechanisms by which a disease agent can evade the immune system,” explained Brayton. “In the simplest terms, immune responses start with recognition that a foreign organism is present. Specifically, proteins on or in that organism are detected as foreign, triggering a cascade of events that leads to the organism’s destruction.

 

“If the organism can evade detection, the immune system misses it and persistent infection results,” she said.

The organism typically evades the host immune response by varying the proteins on its surface.

 

“If that pathogen can change those proteins faster than they can be recognized, or in some cases even change their shape at a molecular level, the immune system doesn’t find it,” Brayton said. “The immune response can be absent, weak or simply lag too far behind the organism’s ability to change.

 

“What was surprising in the T. equi genome was that there wasn’t an obvious mechanism for immune evasion,” she said. The genome sequence is providing Brayton’s collaborator Donald Knowles, WSU professor and U.S. Department of Agriculture scientist, the tools to begin to tease apart the mechanism that T. equi uses to persist in the host.

Proteins that do not stimulate a robust response from the host are more difficult to detect with conventional methodologies. However, if one has the entire DNA sequence of the organism, one has the code for every protein that organism can produce. From there, scientists can look for a protein, or set of proteins, that can stimulate enough of a response to be the basis for a vaccine.

 

Brayton is actively engaged in employing her wealth of genomic data to answer questions about how these pathogens persist in their hosts, how they are transmitted, what makes them pathogenic and how to discover good vaccine candidates.

 

Her genome sequences have been published in various journals, including the Proceedings of the National Academy of Sciences, BMC Genomics and the Journal of General Virology.

 

 

 

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Contact:
Charlie Powell, Public Information Officer, WSU College of Veterinary Medicine, 509-335-7073, cpowell@vetmed.wsu.edu