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Efflux inhibition by selective serotonin reuptake inhibitors in Escherichia coli
Abstract
OBJECTIVES: To evaluate the antimicrobial and synergistic (hypothetically due to the inhibition of efflux pumps) effects of selective serotonin reuptake inhibitors (SSRIs) in Escherichia coli strains overproducing various resistance-nodulation-division (RND) efflux pumps. METHODS: MICs of various SSRIs and of clinically relevant antibiotics in the presence and absence of sertraline were determined for E. coli strains overproducing the RND efflux pumps AcrAB, AcrEF, MdtEF and MexAB. The effect of sertraline on Nile red efflux was evaluated in a real-time efflux assay. Expression of marA and acrB was monitored using quantitative RT-PCR. RESULTS: In MIC assays there was limited synergy of sertraline with tetracycline, oxacillin, linezolid and clarithromycin, depending on the individual pump overexpressed and on whether rich or minimal medium was used. Sertraline, as the most potent SSRI with regard to bacterial growth inhibition, led to rapid dose-dependent Nile red efflux inhibition, and was also found to increase the expression of marA and acrB. CONCLUSIONS: A possible explanation for the discrepancy between the MIC and real-time efflux assays was that sertraline is a weak inducer of marA and acrB, thereby reducing its initial antibacterial and sensitizing effects over time. The results indicate that sertraline may be useful as a model efflux pump inhibitor for in vitro short-term experiments in E. coli, but is unlikely to be clinically useful as a co-drug against Gram-negative bacteria.
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“In addition, the antimicrobial activity of some antidepressants has been confirmed by the synergistic effect of some SSRIs in combination with antibiotics, as well as their effects against some antibiotic-resistant bacteria (Bohnert et al., 2011;Munoz-Bellido et al., 1996, 2000).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Bohnert et al., 2011
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Has the era of untreatable infections arrived?
Livermore, D. M. (2009) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkp255 · Cited by 619
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Antimicrobial activity of psychotropic drugs
Munoz-Bellido, J. L., Munoz-Criado, S., & Garcı̀a-Rodrı̀guez, J. A. (2000) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(99)00154-5 · Cited by 249
Chimeric Analysis of the Multicomponent Multidrug Efflux Transporters from Gram-Negative Bacteria
Tikhonova, E. B., Wang, Q., & Zgurskaya, H. I. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.23.6499-6507.2002 · Cited by 160
Bohnert, J. A., Karamian, B. A., & Nikaido, H. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00620-10 · Cited by 155
Self-citationJellen-Ritter, A., & Kern, W. V. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.5.1467-1472.2001 · Cited by 150
Self-citationNon-Target Gene Mutations in the Development of Fluoroquinolone Resistance in Escherichia coli
Kern, W. V., Oethinger, M. D., Jellen-Ritter, A., & Levy, S. B. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.4.814-820.2000 · Cited by 140
Self-citationReversal of resistance in microorganisms by help of non-antibiotics
Kristiansen, J. E., Hendricks, O., Delvin, T., Butterworth, T. S., Aagaard, L., Christensen, J. B., Flores, V. C., & Keyzer, H. (2007) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkm071 · Cited by 109
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria
Li, X.-Z., Plésiat, P., & Nikaido, H. (2015) · Clinical Microbiology Reviews · doi:10.1128/cmr.00117-14 · Cited by 1,648
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“confirmed by the synergistic effect of some SSRIs in combination with antibiotics; as well as their effects against some antibiotic-resistant bacteria (Bohnert et al., 2011; Munoz-Bellido et al., 1996, 2000).”
BackgroundRND-type drug efflux pumps from Gram-negative bacteria: molecular mechanism and inhibition
Venter, H., Mowla, R., Ohene‐Agyei, T., & Ma, S. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00377 · Cited by 286
Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function
Cussotto, S., Strain, C. R., Fouhy, F., Strain, R. G., Peterson, V. L., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2019) · Psychopharmacology · doi:10.1007/s00213-018-5006-5 · Cited by 266
Metadata
- Authors
- Bohnert, J. A., Szymaniak-Vits, M., Schuster, S., & Kern, W. V.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Bohnert, Jürgen A.
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-23
- Volume
- 66
- Issue
- 9
- Pages
- 2057-2060
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- OpenAlex
- W2129997370
- Cited by
- 114
- References
- 15
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 10 · 2022: 13 · 2021: 2 · 2020: 11 · 2019: 6 · 2018: 9 · 2017: 9 · 2016: 7 · 2015: 7 · 2013: 4 · 2012: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- selective serotonin reuptake inhibitors, sertraline, efflux pump inhibition, RND efflux pumps, Escherichia coli, antimicrobial synergy, acrAB, Kahramanmaraş, AcrB, antibiotic resistance, tetracycline, oxacillin, linezolid, clarithromycin
- MeSH terms
- Anti-Bacterial Agents, DNA-Binding Proteins, Dose-Response Relationship, Drug, Drug Synergism, Escherichia coli, Fluorescent Dyes, Membrane Proteins, Microbial Sensitivity Tests, Oxazines, Protein Kinases, Gene Expression Regulation, Bacterial, Selective Serotonin Reuptake Inhibitors, Reverse Transcriptase Polymerase Chain Reaction, Sertraline, Drug Resistance, Multiple, Bacterial, Escherichia coli Proteins
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