A new study has found that a highly antibiotic-resistant strain of the MRSA superbug – methicillin-resistant Staphylococcus aureus — has emerged in livestock over the past 50 years, possibly due to the widespread use of antibiotics in pig farming.
The strain, called CC398, has become the dominant type of MRSA in European cattle over the past fifty years. It is also a growing cause of human MRSA infections.
The study found that CC398 maintained antibiotic resistance for decades in pigs and other farm animals. And it’s able to adapt quickly to human hosts while maintaining that antibiotic resistance.
The results highlight the potential threat that this strain of MRSA poses to public health. It has been associated with an increasing number of human infections, in people who have and have not had direct contact with livestock.
“Historically high levels of antibiotic use may have led to the evolution of this highly antibiotic-resistant strain of MRSA in pig farms,” said study lead author Dr Gemma Murray, previously at the Cambridge University Department of Veterinary Medicine and now at the Wellcome Sanger Institute.
She added: “We found that the antibiotic resistance of this livestock-associated MRSA is extremely stable – it has persisted for several decades, and also as the bacteria has spread to different species of livestock.
The use of antibiotics in European livestock is much lower than it has been in the past. But the researchers say continued reductions in antibiotic use on pig farms – due to recent policy changes – are likely to have a limited impact on the presence of this strain of MRSA in pigs as it is so stable.
Although livestock-associated CC398 is found in a wide range of livestock species, it is most commonly associated with pigs. Its increase was particularly evident in Danish pig farms where the proportion of herds positive for MRSA increased from less than 5% in 2008 to 90% in 2018. MRSA does not cause disease in pigs.
“Understanding the emergence and success of CC398 in European livestock – and its ability to infect humans – is vitally important to managing the risk it poses to public health,” said Dr Lucy Weinert of the Department of Veterinary Medicine, University of Cambridge, senior author of the paper.
The success of CC398 in cattle and its ability to infect humans is linked to three mobile genetic elements in the MRSA genome. These are pieces of genetic material that give MRSA certain characteristics, including its resistance to antibiotics and its ability to evade the human immune system.
Researchers have pieced together the evolutionary history of two particular mobile genetic elements called Tn916 and CCSdude that confer antibiotic resistance to MRSA, and found that they persisted stably in CC398 in pigs for decades. They also persist when CC398 jumps to humans, bringing with them high levels of resistance to antibiotics commonly used in agriculture.
In contrast, a third mobile genetic element called ?Sa3 – which allows MRSA strain CC398 to evade the human immune system – was found to have frequently disappeared and reappeared over time, both in CC398 associated with man and livestock. This suggests that CC398 can adapt quickly to human hosts.
“Cattle-associated MRSA cases in humans still represent only a small fraction of all MRSA cases in human populations, but the fact that they are increasing is a worrying sign,” Weinert said.
The intensification of agriculture, coupled with high levels of antibiotic use in livestock, has raised particular concerns about livestock as reservoirs of antibiotic-resistant human infections.
Zinc oxide has been used for many years in pig farms to prevent diarrhea in piglets. Due to concerns about its impact on the environment and its potential promotion of antibiotic resistance in livestock, the European Union will ban its use from this month. But the authors say this ban may not help reduce the prevalence of CC398 because genes conferring antibiotic resistance are not always linked to genes conferring resistance to zinc treatment.
MRSA was first identified in human patients in 1960. Due to its resistance to antibiotics, it is much more difficult to treat than other bacterial infections. The World Health Organization now considers MRSA to be one of the greatest global threats to human health.