The emergence of antibiotic-resistant, disease-causing bacteria is often due to overuse of antibiotics in humans and livestock. But researchers have set their sights on another potential driver of resistance: antidepressants. We tracked what caused drug resistance in
“Bacteria develop drug resistance to not just one but multiple antibiotics even after several days of exposure,” said lead author Jianhua Guo, who works at the Australian Center for Water and Environmental Biotechnology at the University of Queensland in Brisbane. said. He says it’s both interesting and terrifying.
Globally, antibiotic resistance is a significant public health threat. In 2019, an estimated 1.2 million people died as a direct result of it, with more projected to rise.
early clues
Guo became interested in the potential contribution of non-antibiotic agents to antibiotic resistance in 2014. That’s because research in his lab found that more antibiotic resistance genes circulated in samples of household wastewater than in samples of hospital wastewater, where antibiotic use is high.
Guo’s group and others have also observed that antidepressants, one of the world’s most widely prescribed drugs, kills or inhibits the growth of certain bacteria. They trigger an “SOS response” and trigger cellular defense mechanisms, allowing bacteria to better survive subsequent antibiotic treatment.
In a 2018 paper, the group reported that Escherichia coli It acquired resistance to multiple antibiotics after exposure to fluoxetine, commonly marketed as Prozac. In the latest study, he looked at 13 antibiotics from his five other antidepressants and six of his drugs to explore how antidepressant resistance manifests itself. Escherichia coli developed.
In bacteria grown in well-oxygenated laboratory conditions, antidepressants caused cells to generate reactive oxygen species. It is a toxic molecule that activates microbial defense mechanisms. Most notably, this activated the bacterial efflux pump system. This is a common efflux system that many bacteria use to eliminate various molecules, including antibiotics. This probably explains why bacteria were able to tolerate antibiotics without having specific resistance genes.
but exposure Escherichia coli The shift to antidepressants has also led to increased microbial mutation rates and subsequent selection of various resistance genes. However, bacteria grown under anaerobic conditions had much lower levels of reactive oxygen species and developed antibiotic resistance much slower.
In addition, at least one antidepressant, sertraline, facilitated gene transfer between bacterial cells. This is a process that can hasten the spread of resistance throughout a population. Allows resistance to hops in between.
growing awareness
Kiran Patil, who studies microbiome-chemical interactions at the University of Cambridge, UK, has found that over the past five years, many non-antibiotic drugs that target human cells have also affected bacteria, leading to antibiotic resistance. He said there is growing awareness of the potential contribution. “The strength of this study is the mechanistic detail,” says Patil.
To understand how antidepressants promote antibiotic resistance, researchers should use Identifying which molecule in the bacterium the drug targets and the drug’s effect on a broader range of clinically relevant bacterial species. In 2018, Meyer and her colleagues investigated 835 drugs that do not target microbes and found that 24% inhibited the growth of at least one of her strains of human gut bacteria.
Patil and Maier present evidence for assessing the real impact of antidepressants on resistance, including whether antidepressants accumulate antibiotic-resistant bacteria, particularly disease-causing bacteria, in humans, animals, or the environment. said that it is important to collect
Significant amounts of antidepressants have been found in wastewater, but reported levels tend to be below the concentrations at which Guo’s group observed significant effects. Escherichia coliHowever, some of the antidepressants that showed strong effects in this study would be expected to reach that concentration in the large intestine of people taking the drug.
Follow-up survey
According to Meyer, some studies are now linking antidepressants and other non-antibiotic medications to changes in bacteria, and how such drugs affect the microbiome of people taking them. Preliminary research gives a ‘first hint’ of what might be affected.
However, in healthy people Escherichia coli Meyer says it is primarily found in the large intestine, where anaerobic conditions exist, so it is possible that the processes described in this paper do not occur at the same rate in humans. Bacterial growth conditions should be used that model the possible site of action of the depressant, Patil said.
Guo said his lab is currently examining the microbiome of mice given antidepressants. Early unpublished data suggest that drugs can alter the gut microbiota of animals and facilitate gene transfer.
But Guo and Maier caution people not to stop taking antidepressants based on this research. “If you have depression, you need to treat it in the best way possible. Bacteria are next,” says Meyer.
Researchers and pharmaceutical companies need to quantify the contribution of non-antibiotic drugs to antibiotic resistance, says Guo. “Non-antibiotic drugs are a big concern that we shouldn’t overlook,” he says.
This article is reproduced with permission and was first published on January 24, 2023.
