by The widespread use of antibiotics in agriculture has led to the emergence of bacteria that are more resistant to the human immune system, scientists have warned.
Research suggests that the antimicrobial colistin, used for decades as a growth promoter in pig and chicken farms in China, has led to the emergence of AND coli strains that are more likely to evade our immune system’s first line of defense.
Although colistin is now banned as a livestock feed additive in China and many other countries, the findings raise an alarm about a significant new threat posed by the overuse of antibiotic drugs.
“This is potentially much more dangerous than antibiotic resistance,” said Prof. Craig MacLean, who led the research at the University of Oxford. “It highlights the danger of the indiscriminate use of antimicrobials in agriculture. We accidentally ended up compromising our immune systems to get fatter chickens.
The findings could also have significant implications for the development of new antibiotic drugs in the same class as colistin, known as antimicrobial peptides (AMPs), which the scientists say could pose a particular risk of compromising innate immunity.
AMPs are compounds produced by most living organisms in their innate immune response, which is the first line of defense against infection. Colistin is based on a bacterial AMP – microbes use the compounds to protect themselves from competitors – but it is chemically similar to some AMPs produced in the human immune system.
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The extensive use of colistin in livestock since the 1980s has triggered the emergence and spread of AND coli bacteria carrying colistin resistance genes, ultimately leading to widespread restrictions on the drug’s use in agriculture. But the latest study suggests that the same genes also allow pathogens to more easily evade the AMPs that form a cornerstone of our own immune response.
In the studio, AND coli carriers of a resistance gene, called MCR-1, have been exposed to AMPs known to play important roles in innate immunity in chickens, pigs and humans. The bacteria were also tested for their susceptibility to human blood serum.
Scientists have found out AND coli carriers of the MCR-1 gene were at least twice as resistant to being killed by human serum. On average, the gene increased human and animal AMP resistance by 62% compared to bacteria lacking the gene. The study, published in the journal eLife, also demonstrated that the resistant AND coli was twice as likely to kill moth larvae injected with the infection, compared to the control AND coli put under tension.
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MacLean said it is not possible to estimate how this might translate into real-world consequences, such as the risk of a AND coli infection leading to sepsis and death. And the prevalence of these strains of AND coli have declined sharply since China banned the use of colistin as a growth promoter, suggesting that these genes pose other “fitness disadvantages” for pathogens. However, the findings highlight a fundamental risk that has not yet been widely considered.
“The danger is that if bacteria develop resistance to [AMP-based drugs]it could also make bacteria resistant to one of the pillars of our immune system,” MacLean said.
Antimicrobial resistance poses a dire global threat — the United Nations has warned that up to 10 million people a year could die from superbugs by 2050 — and so the need for new antibiotics is pressing. There is growing interest in the potential of AMPs as drugs, and some of those under development include drugs based on human AMPs.
MacLean and colleagues are not calling for halting development of such drugs, but say extremely careful risk assessments are needed on the likelihood of resistance emerging and the potential consequences. “For MPAs, there are potentially very serious negative consequences,” she said.
Dr Jessica Blair, from the University of Birmingham, who was not involved in the study, said: ‘Antimicrobial peptides, including colistin, have been heralded as a potential part of the solution to the rise in multidrug-resistant infections. This study, however, suggests that resistance to these antimicrobials may have unintended consequences on the ability of pathogens to cause infection and survive within the host.”
Dr. George Tegos, of New York’s Mohawk Valley Health System, said no broad conclusions about the potential risks of AMPs could be drawn from a single study, but added that the findings “raise reasonable and sensible concerns.”
Cóilín Nunan, consultant to the Alliance to Save Our Antibiotics, who was not involved in the study, said: ‘This new study shows that colistin resistance is probably even more dangerous than previously thought… It is also remarkable that the UK government is still against banning the mass preventive medication of intensively farmed animals with antibiotics, even though the EU banned their use more than a year ago.”
