Article: How antidepressants help bacteria resist antibiotics

[Andy]

"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."

.....

"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."

https://www.nature.com/articles/d41586-023-00186-y

 

[Andy]

Antidepressants can induce mutation and enhance persistence toward multiple antibiotics, 2023, Guo et al

Significance
Antibiotic resistance is a global threat to public health and associated with the overuse of antibiotics. Although non-antibiotic drugs occupy 95% of the drug market, their impact on the emergence and spread of antibiotic resistance remains unclear. Here we demonstrate that antidepressants, one of the most frequently prescribed drugs, can induce antibiotic resistance and persistence. Such effects are associated with increased reactive oxygen species, enhanced stress signature responses, and stimulation of efflux pump expression. Mathematical modeling also supported a role for antidepressants in the occurrence of antibiotic-resistant mutants and persister cells. Considering the high consumption of antidepressants (16,850 kg annually in the United States alone), our findings highlight the need to re-evaluate the antibiotic-like side effects of antidepressants.

Abstract
Antibiotic resistance is an urgent threat to global health. Antidepressants are consumed in large quantities, with a similar pharmaceutical market share (4.8%) to antibiotics (5%). While antibiotics are acknowledged as the major driver of increasing antibiotic resistance, little attention is paid to the contribution of antidepressants in this process. Here, we demonstrate that antidepressants at clinically relevant concentrations induce resistance to multiple antibiotics, even following short periods of exposure. Antibiotic persistence was also enhanced. Phenotypic and genotypic analyses revealed the enhanced production of reactive oxygen species following exposure to antidepressants was directly associated with increased resistance. An enhanced stress signature response and stimulation of efflux pump expression were also associated with increased resistance and persistence. Mathematical modeling also predicted that antidepressants would accelerate the emergence of antibiotic-resistant bacteria, and persister cells would help to maintain the resistance. Overall, our findings highlight the antibiotic resistance risk caused by antidepressants.

Paywall, https://www.pnas.org/doi/10.1073/pnas.2208344120

 

[Peter T]

The Nature article just mentions fluoxetine and sertraline by name, though it also refers to ‘five other antidepressants’ in the sentence mentioning fluoxetine and I have not checked the source articles. However ‘antidepressants’ potentially covers quite a diverse range of pharmaceuticals, which raises the possibility that this encouragement of antibiotic resistance in bacteria is not specific to antidepressants alone but may also result from other drugs.