Mycoplasma Bovis: A Challenging Pathogen.

 By Heather Smith Thomas.

 Mycoplasma bovis is a devastating and often overlooked pathogen that affects cattle and bison.  In cattle, it can cause many diseases, including mastitis in dairy cows, arthritis in cows and calves, pneumonia in calves, and infections that may cause late-term abortion. Not all infected animals get sick.  Most of them shed the bacteria without signs.

Dr. Murray Jelinski, Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, says there are many different types of mycoplasmas that infect other animals and humans, but tend to be specific to each host.  “Cattle can have several types including Mycoplasma bovirhinis and M. canis, but those are not pathogenic.  We find them in cattle but they are not a cause of disease.  The one that concerns us is M. bovis.  The first cases in cattle in North America were reported in the early 1960’s—and associated with arthritis and mastitis.  The first case of M. bovis was mastitis in a dairy cow in California, and the pathogen was named Mycoplasma agalactia var bovis,” he says.  

“Later it was just called M. bovis and we started to see more cases where it was involved with arthritis.  If you look back in European literature from the 1950’s people were talking about this organism, but no one knew what it was.  Then it was found in some cases of arthritis in Canada and the U.S.  In the 1980’s there were more reports and people were wondering if M. bovis might be involved in pneumonia.  They already knew it could cause mastitis in lactating cows, and pneumonia in calves—particularly dairy calves where the housing wasn’t ideal,” says Jelinski.

Dr. Jennifer Davies, University of Calgary, is a pathologist and director of the diagnostic lab at the University.  “This disease manifests in different ways, depending on the production system and age of the animal.  This bacterium can affect all age groups in beef (cow-calf and feedlot) and dairy, but the manifestations are different,” she says.

In feedlot beef animals it causes chronic disease that is poorly responsive to antibiotic therapy.  In dairy cattle, M. bovis is a significant player in mastitis.  This could also occur in beef cows but is seen more often in dairy cows because of the way they are managed and the fact they have more mammary tissue.

“This bacterium is quite different from other bacterial agents that cause respiratory disease or mastitis.  It is the smallest living organism that can replicate.   Along with tiny size, these bacteria lost a lot of their genetic material as they evolved.  They can’t produce the products they need to survive on their own and are dependent on living in a host that can provide what they need.  The good news is that they don’t survive very well out in the environment.  They survive on mucous membranes of cattle, particularly in the nasal cavities,” she explains.  Thus these bacteria are mainly spread from one animal to another by direct contact, though they may live long enough on feed or in water to be transmitted to another animal.

M. bovis is also different than most other bacteria in that it is extremely good at evading the immune system.  “As a result, the body cannot clear the infection.  Coupled with the fact that this organism is not particularly responsive to most antibiotics we use, it may become a chronic pneumonia or chronic mastitis,” she says.

Because of their structure, Mycoplasma bacteria often don’t elicit much immune response, and it may take a while for signs of disease to appear.  This pathogen multiplies very slowly.  “The slower the organism grows, the less robust the immune response will be in the body.  It’s quiet and sneaky, like tuberculosis,” Jelinski says.

“Mycoplasmas are the smallest self-replicating bacteria.  They don’t even have a well-defined cell wall; they don’t have many of the regular metabolic genes to keep them going.  One of the problems we have is that they are really hard to culture because they grow so slowly.  It can be hard to find them in a tissue sample because they are so hard to culture if you are not used to working with them,” he explains.  

This bacterium also keeps changing its surface proteins.  “The immune system might have recognized it last week but can’t recognize it this week.  Mycoplasma are very adaptable and this is one reason they create chronic infections,” says Jelinski.  This also enables them to be resistant to antibiotics.

If these bacteria get into the bloodstream they can go to many other places in the body, but often end up in the large joints, like the stifle.  “This is when the animal gets arthritis,” says Davies.  “There is inflammatory reaction in the joint and the inflammation often includes the tendons and tissue around the joints.  This results in severe and chronic lameness, which also does not respond to treatment very well,” she says.

“In the dairy industry there is increasing incidence of Mycoplasma bovis in cases of mastitis, and that’s a problem,” says Jelinski.  “Just like in the lungs, once it gets in the udder it is very difficult—if not impossible—to treat.  Yet it is still a small percentage of the total cases of mastitis in the world,” he says.

Dr. Chris Chase, Department of Veterinary and Biomedical Sciences, South Dakota State University, says this bacterium is not very well understood in terms of how it evades the immune system and is unresponsive to antibiotics.  “In the pig industry Mycoplasma hyopneumoniae is a big issue and presents a different picture than M. bovis and causes a pneumonia that isn’t quite as chronic and doesn’t form all the little abscesses in the lungs that we see in cattle.  It took researchers 20 years to come up with the basic knowledge about the disease in pigs to develop a vaccine, with many people working on it, and we don’t have nearly as much research on M. bovis in cattle,” he says.

“We started seeing it in baby calves in North Dakota in the mid 1990’s.  Those calves had a droopy ear and head tilt (like they had a head cold or ear infection).  When we necropsied and cultured those, we got a pure culture of M. bovis but in recent years it seems that M. bovis has become more virulent.  It has gone from being a secondary problem (after initial infection with something else) to a primary problem in young calves,” Chase says.

Dairy calves are susceptible, especially if they may consume milk that contains the pathogen, since M. bovis often causes mastitis in dairy cows.  “If we see the head tilt in dairy calves we’d just assume they ingested the pathogen from waste milk (if a dairy feeds milk from mastitis cows to calves).  Seeing it in beef calves, however, told us that can’t always be the case because beef cows rarely get Mycoplasma mastitis.”

These infections are difficult to successfully treat; there are no really good antibiotics that work, or vaccines.  “Some people resort to using autogenous vaccines.  There was a commercial vaccine marketed for a while with a conditional license, but none of the vaccines have been shown to be very efficacious; we don’t know what’s important to include in a vaccine.  There are multiple strains of these bacteria, so some people when they make the vaccines put 3 to 10 different strains in it, hoping they might be able to cover most of the ones that could be causing problems,” he says.

This is a frustrating challenge because we don’t know what the best antigen would be, to include in a vaccine.  “It’s not like other bacteria that cause pneumonia.  It took us a long time to figure out how to grow M. bovis in culture, and it grows very slowly and is more difficult.”  

Researchers figured out a way to grow the Mycoplasma bacterium that causes disease in pigs, and get the right antigen and make it do what they need it to do for a vaccine, but no one has been able to do that yet with M. bovis.  It is one thing to culture it, but it’s a whole different challenge to grow it and make it good for a vaccine. The slower the organism grows, the less aggressive the immune response will be in the body.  This pathogen is very quiet and sneaky.

“Also we don’t have any antibiotics that do a good job with it, partly because it grows so slowly, and it doesn’t have a cell wall.  We can’t use something like penicillin that affects the cell wall, and it’s not a gram negative.  It’s not a typical bacterium, so our antibiotics are not affective against it,” says Chase.
Many antibiotics are effective against fast-growing bacteria and since M. bovis grows slowly, those antibiotics are ineffective.  “There are many things about this pathogen that make it resistant to our efforts to treat the animal.”