Although modern medicine has led to the spread of resistant staphylococci, the use of antibiotics apparently did not produce the notorious germs: They emerged naturally in hedgehogs 200 years ago, according to a study. Presumably, a skin fungus in these wild animals was responsible for this, which produces an antimicrobial substance to assert itself against bacteria. In contrast, Staphylococcus aureus developed resistance early on. But the results suggest that it was not until the era of antibiotics that the resistant strains were able to spread to humans and livestock.
The former miracle weapons of medicine are losing their effectiveness: Antibiotic-resistant bacteria are considered to be one of the greatest threats in the fight against infectious diseases. The spread of these pathogens has to do with a basic evolutionary principle. Because through the sometimes wasteful use of antibiotics in medicine and livestock farming, humans expose bacteria to permanent selection pressure: microbes with genetically determined resistance to the active ingredients can survive and then advance to become the dominant form of pathogen. The methicillin-resistant strains of Staphylococcus aureus (MRSA) are particularly notorious in this context. If these pathogens, also known as hospital germs, spread in the human body, there are hardly any treatment options and there is a threat to life.
It was previously assumed that these resistant bacteria developed through the massive use of penicillin and later through the use of other antibiotics in livestock or humans. However, an earlier emergence also seemed possible: because almost all antibiotics are originally natural active ingredients with which fungi, for example, try to prevail against bacterial competitors. Thus, bacteria could naturally have developed strategies against these active ingredients. In this context, an international research team has now followed a lead: Studies have shown that hedgehogs also carry MRSA bacteria.
Resistance with a spiky history?
As part of their study, the researchers sequenced and analyzed more than 1000 S. aureus isolates from hedgehogs from different areas of their range. As a result, they were initially able to prove more precisely that the animals often carry a strain of MRSA, which is referred to as mecC-MRSA. By examining certain characteristics in the genome of these pathogens, they then investigated the question of when they might have produced their resistance genes. In addition, the researchers set out to search for possible drivers of the development of the resistant strains in the prickly fellows.
“Using sequencing technology, we traced the genes that give mecC-MRSA bacteria their antibiotic resistance back to when they first appeared and found that they apparently existed as early as the 19th century,” says senior author Ewan Harrison of the University of Cambridge. Thus, they existed well before the clinical use of the first antibiotics. “Our study shows that the use of penicillin was not responsible for the initial occurrence of MRSA, but a natural biological process. We believe that MRSA later spread to livestock and humans through direct contact, ”says the scientist. At least some of the current antibiotic-resistant strains of bacteria could come from hedgehogs, the results suggest.
Cause: natural competition
But why did the super germs develop in these animals of all places? The study shows that a skin fungus could have been responsible for this: the pathogen Trichophyton erinacei is widespread in hedgehogs. The researchers were able to prove that this fungus produces antimicrobial substances whose effects are based on a principle similar to that of penicillin and other antibiotics. Co-cultivations of the fungus with different S. aureus strains made it clear: In methicillin-sensitive versions, a bacteria-free zone of inhibition developed around Trichophyton erinacei – the resistant MRSA bacteria, on the other hand, grow undisturbed in the vicinity of the fungus. “We therefore believe that the MRSA strains developed on the skin of hedgehogs during the struggle for survival,” says Harrison.
According to the researchers, however, the results are no reason to fear hedgehogs. Because direct transmissions of MRSA bacteria from these animals to humans are probably rather rare. However, they see the study results again as a warning to use antibiotics cautiously so as not to promote the spread of resistant strains: “We have to be careful when using antibiotics. There is a large ‘reservoir’ in the animal world in which antibiotic-resistant bacteria can survive – and from there it is only a small step until they are ingested by farm animals and then infect humans, “says co-author Mark Holmes of the Cambridge University. “Wild animals, farm animals and humans are all interconnected: We share an ecosystem. It is not possible to understand the development of antibiotic resistance if one does not look at the entire system, ”concludes the scientist.
Source: University of Cambridge, Articles: Nature, doi: 10.1038 / s41586-021-04265-w