Highly antibiotic-resistant strain of MRSA that arose in pigs can jump to humans
A new study has shown that a highly antibiotic-resistant strain of the superbugs MRSA-methicillin-resistant Staphylococcus aureus-has emerged in livestock over the past 50 years, probably as a result of the widespread use of antibiotics in pig farming.
The strain, called CC398, has become the dominant type of MRSA in European livestock over the past fifty years. It is also a growing cause of human MRSA infections.
The study found that CC398 has maintained its antibiotic resistance in pigs and other livestock for decades. And it is able to quickly adapt to human hosts while maintaining this antibiotic resistance.
The results highlight the potential threat this MRSA strain poses to public health. It has been linked to an increasing number of human infections, in people who may or may not have had direct contact with livestock.
“Historically high levels of antibiotic use may have led to the evolution of this highly antibiotic-resistant MRSA strain on pig farms,” said Dr. Gemma Murray, a lead author of the study, previously in the Department of Veterinary Medicine at the University of Cambridge and now at the Wellcome Sanger Institute.
She added: “We found that the antibiotic resistance in this livestock-related MRSA is extremely stable — it’s been going on for decades, and also because the bacteria has spread across different animal species.”
The use of antibiotics in European livestock is much lower than in the past. But the researchers say the continued reduction in antibiotic use on pig farms – as a result of recent policy changes – will likely have limited impact on the presence of this MRSA strain in pigs because it is so stable.
Although cattle-associated CC398 is found in a wide variety of animal species, it is most commonly associated with pigs. The increase is particularly evident in Danish pig farms where the proportion of MRSA positive herds has 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 farming – and its ability to infect humans – is vital in managing the risk it poses to public health,” said Dr. Lucy Weinert of the University of Cambridge’s Department of Veterinary Medicine, senior author of the paper.
CC398’s success in livestock and its ability to infect humans is linked to three mobile genetic elements in the MRSA genome. These are chunks of genetic material that give the MRSA certain characteristics, including antibiotic resistance and the ability to evade the human immune system.
The researchers reconstructed the evolutionary history of two specific mobile genetic elements called Tn916 and SCCmec that confer antibiotic resistance in MRSA, and found that they were stable in CC398 in pigs for decades. They also persist when CC398 jumps to humans, carrying with it a high degree of resistance to antibiotics commonly used in agriculture.
In contrast, a third mobile genetic element called φSa3, which allows the CC398 strain of MRSA to evade the human immune system, has often disappeared and reappeared over time in both the human-associated and livestock-associated CC398. . This suggests that CC398 can quickly adapt to human hosts.
“Cases of livestock-related MRSA 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.
Intensification of agriculture, combined with high antibiotic use in livestock, has raised particular concerns about livestock as a reservoir of antibiotic-resistant human infections.
Zinc oxide has been used for years on pig farms to prevent diarrhea in piglets. Due to concerns about its environmental impact and possible 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 the genes conferring antibiotic resistance are not always linked to the genes conferring resistance to zinc treatment.
MRSA was first diagnosed 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 one of the world’s greatest threats to human health.
The findings are published today in the journal eLife†
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Marta Matuszewska et al, Stable antibiotic resistance and rapid human adaptation in livestock-associated MRSA, eLife (2022). DOI: 10.7554/eLife.74819
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