Jianhua Guo is a professor at the Australian Center for Water Environmental Biotechnology. His research focuses on the removal of contaminants from wastewater and the environmental aspects of antimicrobial resistance. One of these aspects is the overuse of antibiotics that promotes resistance to these drugs.
Guo wondered if the same could be true for other types of drugs. His lab has found that they definitely are. Certain antidepressants (SSRIs and SNRIs) promote resistance to different classes of antibiotics. This resistance is inherited for 33 generations of bacteria, even after the antidepressants are removed.
so much work
Antidepressants are among the most prescribed and taken drugs. They account for about 5% of the pharmaceutical market share, about the same as antibiotics. It also accounts for four of the top 10 most-prescribed psychiatric drugs in the United States.
Guo’s lab grew to assess the potential impact of antidepressants on antibiotic resistance. Escherichia coli We measured how well bacteria grew on agar plates infused with various antibiotics for 60 days in the presence of physiologically relevant concentrations of five commonly prescribed antidepressants. They looked at antibiotics with different mechanisms of action. Some inhibit her DNA synthesis of bacteria, some inhibit protein synthesis, some inhibit cell wall synthesis, and so on. They found that the antidepressants they tested induced resistance to multiple antibiotics within a day.
The group did a number of experiments trying to determine how this happened, starting with sequencing the DNA, mRNA, and protein of antibiotic-resistant bacteria. caused bacteria to produce reactive oxygen species, which can damage cellular components. The drug also caused the bacteria to express more of an efflux pump protein that pumps the antibiotic out of the cell. Genetic mutations in bacterial chromosomes that promote multidrug resistance were also more common.
The scientists then looked at time-lapse microscopy images of DNA moving between bacterial cells, a process that allows resistance genes to spread rapidly. guess what? SSRIs accelerated it, increased its occurrence, and allowed resistant strains to spread horizontally to their peers (in addition to vertically to progeny).
Persistence can lead to resistance
Antidepressants also increased the proportion of bacterial cells that persisted in the presence of high concentrations of antibiotics. I don’t have any genetic mutations. They are still normal bacteria. They’re just randomly more resistant to antibiotics than their peers. Researchers have generated a mathematical model of bacterial evolution. This suggests that antidepressants enhance the rate at which both normal and persistent bacteria evolve into full-fledged multidrug-resistant strains.
Antibiotic resistance is a major threat to human health. Antidepressants are prescribed and used in such high volumes that the fact that they can induce antibiotic resistance should not be considered a minor side effect. It may also be taken into account in the design of new, more effective antidepressants.
PNAS2023 Doi: 10.1073/pnas.2208344120
