Antidepressants help bacteria resist antibiotics

In the presence of antidepressants, the Gram-negative bacterium E. coli can fend off antibiotics.
— Credit: Steve Gschmeissner/Science Photo Library

Liam Drew writes in Nature:

The emergence of disease-causing bacteria that are resistant to antibiotics is often attributed to the overuse of antibiotics in people and livestock. But researchers have homed in on another potential driver of resistance: antidepressants. By studying bacteria grown in the laboratory, a team has now tracked how antidepressants can trigger drug resistance¹.

“Even after a few days exposure, bacteria develop drug resistance, not only against one but multiple antibiotics,” says senior author Jianhua Guo, who works at the Australian Centre for Water and Environmental Biotechnology at the University of Queensland in Brisbane. This is both interesting and scary, he says.

Globally, antibiotic resistance is a significant public-health threat. An estimated 1.2 million people died as a direct result of it in 2019², and that number is predicted to climb.

Early clues

Guo became interested in the possible contributions of non-antibiotic drugs to antibiotic resistance in 2014, after work by his lab found more antibiotic-resistance genes circulating in domestic wastewater samples than in samples of wastewater from hospitals, where antibiotic use is higher.

Guo’s group and other teams also observed that antidepressants — which are among the most widely prescribed medicines in the world — killed or stunted the growth of certain bacteria. They provoke “an SOS response”, Guo explains, triggering cellular defence mechanisms that, in turn, make the bacteria better able to survive subsequent antibiotic treatment.

In a 2018 paper, the group reported that Escherichia coli became resistant to multiple antibiotics after being exposed to fluoxetine³, which is commonly sold as Prozac. The latest study examined 5 other antidepressants and 13 antibiotics from 6 classes of such drugs and investigated how resistance in E. coli developed.

In bacteria grown in well-oxygenated laboratory conditions, the antidepressants caused the cells to generate reactive oxygen species: toxic molecules that activated the microbe’s defence mechanisms. Most prominently, this activated the bacteria’s efflux pump systems, a general expulsion system that many bacteria use to eliminate various molecules, including antibiotics. This probably explains how the bacteria could withstand the antibiotics without having specific resistance genes.

But exposure of E. coli to antidepressants also led to an increase in . . .

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