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New research uncovers genetic resistance to salmonella

Heather Smith Thomas Published on 24 March 2013

As we learn more about the genetics of cattle and gain the tools to find specific genes that affect various traits and differences in animals, we are developing the ability to test individuals and select for (or against) certain traits.

Steve Carlson, DVM, Ph.D. and Tim Day, Ph.D., both at Iowa State University, are involved with a company founded four years ago called PSR Genetics, in Scott City, Kansas. PSR stands for Phenotype Salmonella Resistant.

The company is based on a proprietary genetics platform that allows them to uncover what are termed SNPs (single nucleotide polymorphisms).

Steve Carlson speaks at a conference about salmonella-resistant genetics.

“These are small genetic changes that can often lead to significant changes in the animal,” explains Carlson, who has studied salmonella for most of his career.

Through his earlier experiences working with the USDA, he performed a number of infection experiments in cattle, using salmonella. Along the way, he would occasionally notice an animal that was hard to infect. These individuals had more natural resistance.

“Those animals always seemed to be non-black,” he said. “They might be Red Angus, Hereford, Red and White Holsteins, Shorthorn, Piedmontese, Tarentaise, Salers, Simmental, etc.

We haven’t tested Charolais yet, but that would be another breed possibly exhibiting resistance.”

The new company used this information to find a SNP that led to this resistance. “I guided a number of experiments, which did indeed show significant and natural resistance through what they called the PSR SNP,” Carlson said.

The company first started looking at dairy cattle, since salmonella in dairy animals can be a significant and insidious problem.

But they couldn’t find many Red and White Holsteins that had two copies of the PSR SNP. So they began looking at beef cattle, where it does seem to be more prevalent in the non-black cattle.

First came testing in the lab, using blood cells from various animals. “Salmonella resistance is fairly easy to determine with blood cells because salmonella likes to physically invade cells.

This was an easy way to screen for this trait, just using blood samples from cattle and counting the salmonella invading these cells,” Carlson says.

The next step was to infect the cattle with strains of salmonella that are quite virulent or even lethal. After being experimentally infected with a virulent strain of salmonella, the cattle lacking any copies of the PSR gene were so ill they had to be euthanized within three days.

Cattle with one copy of the gene were susceptible but resisted illness and death for twice as long. Black cattle with two copies of the gene survived the infection for up to 10 days.

Non-black cattle with two copies of the gene were significantly more resistant, and the researchers could not produce illness (nor any shedding in feces) in these animals, even when using 10 times the typical challenge dose of bacteria.

“The non-black genotype and phenotype has been worked out through a number of other researchers. It is conferred through a gene called MCR.

Non-black is a recessive phenotype; you must have two recessive alleles (one from each parent) for the animal to be non-black,” says Carlson.

Other researchers have uncovered many interesting things about the MCR genes. The dominant MCR gene encodes a receptor that is needed for black pigmentation and also has other functions.

The recessive mcr/mcr cattle are not only non-black, but research has suggested that they metabolize antibiotics faster (thus shorter withdrawal time) and also have an elevated pain threshold – and thus are less likely to go off feed when illness strikes.

“Salmonella lethality is not of huge economic importance in cattle. What may be more important is the fact that the cattle with less resistance may have the bacterium in their intestines and shed it and have intermittent diarrhea,” Carlson says.

The company also did some research looking at less virulent strains of salmonella and lower doses of the pathogen.

Interestingly, they found that these non-black cattle that have two copies of the PSR gene tended to not shed the salmonella when infected and had very few bacteria that would colonize in the intestines; therefore, these resistant cattle would not pass it on to the susceptible cattle.

The few salmonella bacteria found in the intestinal tract of resistant cattle tended to be inactive, not causing disease.

Food safety issues

Next, the company wanted to investigate a new phenomenon with salmonella. Some researchers, primarily at Clay Center, Nebraska, found that at slaughter many cattle lymph nodes contain salmonella, even in healthy animals.

“They found that anywhere from 1 to 30 percent of slaughtered cattle unfortunately contained infected lymph nodes. Anecdotal reports suggest that these numbers may be even higher in some localities,” says Carlson.

“What probably happens is these cattle get a low-grade salmonella infection in their intestines and the immune system cells try to take care of it by engulfing the salmonella bacteria and escorting them off to the lymph nodes, where the immune system is supposed to kill the bacteria.

But salmonella is really good at resisting this tactic. So all it does is move the salmonella bacteria from the intestinal tract to the lymph nodes.

The problem with this translocation event is that some of these lymph nodes get incorporated into hamburger when the animal is slaughtered and processed,” he says.

“It is unclear why we are just starting to see these problems – whether it’s something new about these particular strains of salmonella or some other unknown factor.

The packers are having difficulty dealing with it even though they are trying very hard to mitigate this problem.

There have been a few hamburger-associated outbreaks in the past few years, and they’ve done a really good job at instituting the recalls and getting rid of that beef,” says Carlson.

PSR Genetics was able to acquire a couple of these problematic salmonella strains from the Clay Center researchers and do an experimental infection.

What they found was that the non-black cattle with two copies of the PSR gene had no detectable salmonella in their lymph nodes.

By contrast, all the other genotypes of cattle they worked with had some salmonella in their lymph nodes.

The next logical step was to look at E. coli because these two bacteria are closely related, and E. coli has become an increasingly prevalent problem in processed meat during the past 20 years.

A genetic test

The company is now working to develop a licensable genetic test that could be offered to cattle producers as a food safety tool to minimize some of these food safety pathogens.

This might be of major interest to producers who are trying to raise natural, healthy beef.

“The beef packers have some issues making this work, mainly because there are so many black cattle produced today,” says Carlson. “Currently, the company is trying to get this genetic test available to producers.

It’s been a bit of a struggle, however, because of the popularity of black cattle. Thus it will probably be more of a niche market for producers who want to market their animals on their own,” says Carlson.

This test might be of interest to producers who are not raising black cattle – to find out if their animals are resistant to two important food safety pathogens, which would be a great marketing tool.

“The company is still working on getting this test to the marketplace. There are a number of producer groups who can help push this forward and will appreciate this kind of test,” he says.  end mark

Heather Smith Thomas is a freelancer based in Idaho.

PHOTO

Steve Carlson speaks to a conference on the research identifying salmonella-resistant genetics. Photo courtesy of PSR Genetics.

/MORE: More research needed

“Black cattle that have 2 copies of the PSR gene are partially resistant to Salmonella; they have a moderate level of resistance.

The PSR gene helps the most, however, in non-black cattle that have 2 copies of the PSR gene,” says Carlson.  nbsp;

The company wants to do further research and is looking for partners to help them look for what they call a complementary genotype.

“Within the black cattle population—since there are so many black ones out there—the researchers feel there could be some animals that have 2 copies of the PSR SNP and also possess a complementary genotype that gives them the full resistance observed in their non-black counterparts.”

This type of research would not be terribly difficult, but it would be laborious and time-consuming, doing laboratory tests with blood from a large number of animals.

At this point they’ve only looked at about 1000 of the approximately 50 million black cattle.  They have just scratched the surface, so even though they’ve not yet found one, a complementary genotype in some of these cattle is possible.

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