Understanding Mycoplasma Bovis

Background

The design of the bovine respiratory tract makes it easy for BRD bacteria like Mannheimia, Pasteurella, Histophilus and Mycoplasma to move deep into the lung and find places to hide and makes it hard for the animal’s immune system to counterattack them. The bovine lung is so susceptible to infection and damage that it has been used as an “animal model” of chronic obstructive pulmonary disease (COPD) in humans.  

Injectable macrolide antibiotics (e.g. Micotil, Hymatil, Tilcomed, Draxxin, Tylosin 200, Zactran, Zuprevo) have allowed veterinarians and feedlot operators to control and treat BRD effectively, because macrolides are preferentially transported to the lung tissue, not randomly distributed through the whole body like some other antibiotics. But BRD bacteria develop resistance when similar antibiotics are used year after year or are used repeatedly in the same animal.  

Genetic testing for AMR is becoming increasingly adopted in human and veterinary medicine. In time, this will become the standard for AMR testing, but first researchers must identify the genes associated with AMR to gain a better understanding of how different strains differ in their virulence, that is, why are some more likely to cause disease than others. This has implications with respect to developing an effective vaccine for mycoplasmosis in cattle, which has eluded researchers and the pharmaceutical industry for decades.

Objectives

• Assess the macrolide resistance of Mycoplasma bovis along the respiratory tract using whole genome sequencing   
• Understand the virulence factors and determine if some strains prefer to infect specific tissues such as lungs or joints 

What They Did

Veterinarians from three large feedlot practices collected deep nasopharyngeal samples from healthy cattle and BRD cases and tissue samples from the lungs and joints of cattle that died or were euthanized due to chronic BRD or arthritis at 31 commercial feedlots in Western Canada between 2006 and 2018. Mycoplasma was cultured, isolated, and tested for resistance to a variety of macrolide antibiotics. Antibiotic resistance was compared between animal type (healthy, sick, or dead), and changes in antibiotic resistance over time were examined. 

What They Learned

Macrolide resistance was highest in Mycoplasma from cattle that died or were euthanized in the chronic pen. For example, Draxxin had the lowest level of macrolide resistance (84%) in Mycoplasma from mortalities. These cattle had typically received and failed to respond to repeated antibiotic treatments, which strongly favored the survival of resistant bacteria. Macrolide resistance was intermediate in sick cattle. These were also likely treated with macrolides at least once, which would also favor the survival of resistant bacteria. Mycoplasma from healthy cattle had the lowest level of macrolide resistance, but resistance was still surprisingly high. For example, Draxxin resistance averaged 30% in Mycoplasma from healthy cattle. Over half of the healthy cattle were sampled on arrival, suggesting that they likely arrived at the feedlot carrying macrolide resistance. 

Micotil was registered in Canada in 1990, long before the first samples were collected in this study in 1990. But Draxxin (fall 2007), Zactran (March 2010) and Zuprevo (June 2012) were all registered after the study started. So, Mycoplasma from cattle that died in 2007-2008 were compared to samples from 2017-18 to see how resistance changed as more macrolide antibiotics became available. Macrolide resistance was significantly higher in Mycoplasma isolated from cattle that died in 2017-18 compared to those that died in 2007-08. Resistance was also highly correlated among the different macrolides; Mycoplasma isolates that were resistant to one macrolide antibiotic were usually resistant to the other macrolides as well.  

It was also found that the M. bovis isolated in the lungs and joints were more genetically similar to each other that the M. bovis isolated from the upper respiratory tract.  

What It Means

The team found valuable information by peering into the DNA of M. bovis which showed a rich collection of genes and genetic markers that could help predict AMR, virulence, the tissue most likely to be infected and whether virulence is capable of being transferred to other mycoplasmas. This all contributes to the knowledge on how we approach antibiotic management. 

Rotating classes of antibiotics may help maintain their effectiveness in the long run. In fact, the antibiotic susceptibility results from this study suggest that oxytetracycline may have been a better choice for treating Mycoplasma than any of the macrolides in recent years. Actual BRD treatment outcomes under different antibiotic treatment regimens would be needed to confirm this. 

While additional research is needed, these preliminary research results are very encouraging and will be useful in informing ongoing efforts to develop an effective M. bovis vaccine.