The emergence of antibiotic-resistant superbugs has long been blamed on the use (or misuse) of antibiotics in humans and livestock. However, a new study published in Nature has upended over 50 years of antibiotic research, now suggesting that MRSA, the most common of the superbugs, first developed resistance to the antibiotic methicillin around 200 years ago. That predates antibiotic use in medical and agricultural settings, and is almost 140 years before Staphylococcus aureus was first detected in human patients in 1960.
If MRSA did not arise from the overuse of antibiotics, then what caused specific S. aureus genes to become resistant to common treatment?
According to a large group of international researchers, the answer to that question is natural biological processes in hedgehogs.
During unrelated hedgehog surveys done from Demark and Sweden, scientists noticed a high prevalence of MRSA-carrying mecC, or mecC-MRSA. Methicillin resistance in S. aureus is mediated by the mecA and mecC genes. Up to 60% of the hedgehogs surveyed carried mecC-MRSA, which causes 1 in 200 of all MRSA infections in humans, although it is almost always transferred via a secondary host. Still, the number was high enough to surprise researchers, who then recorded high levels of MRSA in hedgehogs in Europe and New Zealand, as well.
Using whole-genome sequencing, the team was able to trace the genes that give mecC-MRSA its antibiotic resistance all the way back to first appearance—around the 19th century.
Based on the results, the researchers now believe antibiotic resistance evolved in S. aureus as an adaptation to having to exist side-by-side on the skin of hedgehogs with the fungus Trichophyton erinacei, which produces its own antibiotics.
“Our study suggests that it wasn’t the use of penicillin that drove the initial emergence of MRSA, it was a natural biological process,” said senior author Ewan Harrison, researcher at the Wellcome Sanger Institute and the University of Cambridge. “We think MRSA evolved in a battle for survival on the skin of hedgehogs, and subsequently spread to livestock and humans through direct contact.”
Although the authors say the findings are not a reason to steer clear of hedgehogs. Humans rarely get infections with mecC-MRSA, and if they do, it’s typically through intermediate hosts like dairy cows and other domesticated animals.
Still, the research is clear that hedgehogs are a natural reservoir of zoonotic mecC-MRSA lineages that predate the antibiotic era. But, our spiky friends are not the only ones.
“This study is a stark warning that when we use antibiotics, we have to use them with care. There’s a very big wildlife ‘reservoir’ where antibiotic-resistant bacteria can survive. It isn’t just hedgehogs—all wildlife carries many different types of bacteria, as well as parasites, fungi and viruses,” said senior author Mark Holmes, a researcher in the University of Cambridge’s Department of Veterinary Medicine. “Wild animals, livestock and humans are all interconnected: we all share one ecosystem. It isn’t possible to understand the evolution of antibiotic resistance unless you look at the whole system.”