"Nature" shocked!

Resistance of bacteria to antibiotics can lead to infections in humans

The misuse of antibiotics is accelerating this process, and antibiotic resistance has risen to high-risk levels globally

On 5 January 2022, researchers from the University of Cambridge, the Wellcome Sanger Institute, the Danish National Serum Institute and the Royal Botanic Gardens collaborated to publish a paper on antibiotics titled "Methicillin resistance emerges earlier than Clinical Use of Antibiotics

The study found that superbugs arose in hedgehogs about 200 years ago, before antibiotics were discovered and used

This is the result of co-evolution of Staphylococcus aureus to the hedgehog dermatophyte

The study overturns the widely held view that the misuse of antibiotics led to the emergence of superbugs, because superbugs appeared in hedgehogs long before antibiotics were used, which is more likely a natural evolutionary biological process

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common antibiotic-resistant bacterial pathogens, causing approximately 171,000 invasive infections each year in Europe alone

MRSA was first discovered in 1960 after the introduction of methicillin (celbenin) as an option for the treatment of penicillin S.

Subsequently, methicillin resistance emerged in many S.

Currently, the World Health Organization considers MRSA to be an important threat to human health

Methicillin resistance in S.

mecA and mecC are resistant to almost all β-lactam antibiotics, including penicillinase-intolerant penicillins (such as penicillin G), penicillinase-resistant penicillins (such as methicillin), and cephalosporins (such as cefoxitin)

Surveys of hedgehogs from Denmark and Sweden show surprisingly high prevalence of MRSA carrying mecC (mecC-MRSA), suggesting that the evolution of these bacteria may have been driven by natural selection in wildlife rather than antibiotics as is now commonly believed clinical use

mecC-MRSA is widely distributed in hedgehogs

The researchers first examined the geographic distribution and population structure of mecC-MRSA in European hedgehogs

The researchers analysed 828 samples of the nose, skin and feet of 276 hedgehogs from 16 wildlife rescue centres in 10 European countries and two in New Zealand

Surprisingly, mecC-MRSA was present in England and Wales (66%, 81 out of 123), Czech Republic (50%, 6 out of 12), Denmark (50%, 11 out of 22) only), Portugal (29%, 2 of 7) and New Zealand (6%, 1 of 17)
.

Thus, mecC-MRSA has a broad geographic distribution in hedgehogs
.

T.
erinacei produces β-lactam

The researchers found that Trichophyton erinacei (T.
erinacei) produces two beta-lactam antibiotics, providing a natural selection environment
.

In this setting, MRSA isolates have an advantage over susceptible isolates
.

Simply put, hedgehogs carry fungi and bacteria on their skin, and the two animals have fought a protracted battle for survival
.
Fungi secrete antibiotics to kill bacteria, but bacteria have evolved antibiotic resistance, known as MRSA
.

Evolutionary history of mecC-MRSA

Next, the researchers deduced the evolutionary history of Staphylococcus aureus (methicillin-sensitive S.
aureus, MSSA) CC130, CC425 and CC1943, which constitute the most successful mecC-MRSA clones in Europe
.

To this end, we collected and sequenced 786 mecC-MRSA and 127 MSSA CC130, CC425 and CC1943 isolates to represent known geographic distributions (mainly Western and Central Europe) and hosts (mainly humans, cattle, sheep) , goats and wild animals)
.

The researchers used core genome SNP diversity and isolation dates to infer these isolates, as well as 205 mecC-MRSA and 9 MSSA CC130, CC425, and CC1943 isolates collected from hedgehogs
.

To sequence and analyze the data, the researchers traced the genes that make mecC-MRSA resistant to resistance and traced them back to when they first emerged, finding them in the 19th century
.

This suggests that the initial emergence of MRSA was not caused by penicillin use, but rather a natural biological process
.
Wellcome Sanger and researcher Ewan Harrison, from the University of Cambridge, said: "We think MRSA evolved in a struggle for survival on the hedgehog's skin and then spread to livestock and humans through direct contact
.
" 

Population dynamics of mecC-MRSA

Hedgehogs constitute a large library of mecC-MRSA clones, and mecC-MRSA isolates occur much less frequently in humans, domestic animals, and other wild animals
.

Hedgehog isolates were present in 9 of the 16 mecC-MRSA lineages, including the 8 largest (more than 25 isolates) and the 3 earliest (200-130 years ago) lineages
.

The two largest mecC-MRSA CC130 lineages (CC130:A9 and CC130:A10) accounted for 67% (232 of 344) and 65% (520 of all mecC-MRSA isolates from hedgehogs, humans and other sources, respectively) ), with the widest geographic coverage in Western and Central Europe
.
 

Taken together, these studies suggest that methicillin resistance emerged prior to antibiotic use as a result of a co-evolutionary adaptation of S.
aureus to the hedgehog-colonizing dermatophyte
.

The study overturns the widely held view that the misuse of penicillin led to the emergence of superbugs, because superbugs appeared in hedgehogs long before antibiotics were used, which is more likely a natural evolutionary biological process
.

Since almost all antibiotics we use today come from nature, it is likely that resistance to them already exists in nature
.
In humans or livestock, any overuse of antibiotics will favor resistant strains of bacteria, so it's only a matter of time before antibiotics start to lose their effectiveness
.
"Wildlife, livestock and humans are all interconnected
.

We share an ecosystem
.
Only by looking at the whole system can we understand the evolution of antibiotic resistance
.
"

When we understand the world, we should not be trapped in a corner, let alone think in a static way, because nothing in the world is absolute truth
.

It is worth mentioning that these findings cannot be a reason to fear hedgehogs, as mecC-MRSA is rarely infected in humans and has been present in hedgehogs for over 200 years
.

Not only hedgehogs carry antibiotic-resistant bacteria, all wild animals carry many different types of bacteria, parasites, fungi or viruses and other microbes
.

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