Abstract
Several classes of non-antibiotic drugs, including psychoactive drugs, proton-pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs), and others, appear to have strong antimicrobial properties. We considered whether psychoactive drugs induce the SOS response in E. coli bacteria and, consequently, induce Shiga toxins in Shiga-toxigenic E. coli (STEC). We measured the induction of an SOS response using a recA-lacZ E. coli reporter strain, as RecA is an early, reliable, and quantifiable marker for activation of the SOS stress response pathway. We also measured the production and release of Shiga toxin 2 (Stx2) from a classic E. coli O157:H7 strain, derived from a food-borne outbreak due to spinach. Some, but not all, serotonin selective reuptake inhibitors (SSRIs) and antipsychotic drugs induced an SOS response. The use of SSRIs is widespread and increasing; thus, the use of these antidepressants could account for some cases of hemolytic-uremic syndrome due to STEC and is not attributable to antibiotic administration. SSRIs could have detrimental effects on the normal intestinal microbiome in humans. In addition, as SSRIs are resistant to environmental breakdown, they could have effects on microbial communities, including aquatic ecosystems, long after they have left the human body.
Highlights
Maier et al reported on the effects of more than 1000 drugs commonly used in human medicine and tested them for their ability to inhibit the growth of commensal bacteria in conditions mimicking the gastrointestinal tract [4]
serotonin selective reuptake inhibitors (SSRIs) is shown in Figure 1B, in which paroxetine appeared to induce RecA expression, while duloxetine had a lesser effect on RecA
The 60 and 70 μg/mL concentrations of duloxetine did strongly inhibit bacterial growth, but this growth inhibition was not accompanied by Shiga toxin 2 (Stx2) production
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In the early years of this discovery, the antimicrobial activity was often described enthusiastically, for example, as providing new therapeutic strategies for drug-resistant pathogens These antimicrobial effects of non-antibiotic drugs have been more often regarded negatively because of their ability to disrupt the gut microbiome [3]. Many antibiotics induce the SOS response and often trigger increased Stx toxin production by STEC, which is why the CDC and other public health agencies state that antibiotics are contra-indicated in STEC infection. We tested whether antidepressant medications in the serotonin selective reuptake inhibitor (SSRI) class could activate the SOS response using a recA-lacZ reporter strain as an initial screen. Fluoxetine and paroxetine were the most potent SSRIs as inducers of the SOS response and of Stx toxin production. Together with recent findings that SSRIs are detectable in wastewater effluent and in natural surface waters in many countries, may provide a warning for the possible environmental effects of these drugs long after they have left the human body
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