Abstract
This study investigates the effects of antidepressants fluoxetine, sertraline, and amitriptyline on the development of antibiotic resistance in clinical Acinetobacter baumannii isolates. The isolates were exposed to fluoxetine, sertraline, and amitriptyline for 30 days, respectively. The bacteria that developed resistance to gentamicin, imipenem, colistin, and ciprofloxacin were isolated and expression levels of some antibiotic-resistance genes were determined by quantitative reverse-transcriptase PCR. Before and after the exposure, minimum inhibitory concentration (MIC) values of the bacteria were determined by the microdilution method. The statistical analysis was performed using Student’s t test. A time-dependent increase was observed in the number of bacteria that developed resistance and increased the MIC value. After exposure to fluoxetine and sertraline, decreases were observed for efflux and outer membrane porin genes in isolates that developed colistin resistance, and increases were observed in isolates that developed ciprofloxacin resistance. These observations suggest that these antidepressants have similar effects on the development of resistance. While the exposure to fluoxetine did not result in the development of resistance to imipenem, it was observed after exposure to sertraline and amitriptyline, and a common decrease in ompA gene expression was determined in these isolates. To our knowledge, the comparative effects of selected antidepressants on the development of antibiotic resistance in A. baumannii are reported and presented in the literature here for the first time.
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References
Altamura AC, Moro AR, Percudani M (1994) Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 26(3):201–214. https://doi.org/10.2165/00003088-199426030-00004
Alvano SA, Zieher LM (2020) An updated classification of antidepressants: a proposal to simplify treatment. Pers Med Psychiatry. https://doi.org/10.1016/j.pmip.2019.04.002
Ayaz M, Subhan F, Ahmed J, Khan AU, Ullah F, Ullah I, Ali G, Syed NH, Hussain S (2015) Sertraline enhances the activity of antimicrobial agents against pathogens of clinical relevance. J Biol Res-Thessalon 22(1):4. https://doi.org/10.1186/s40709-015-0028-1
Brooks BW, Foran CM, Richards SM et al (2003) Aquatic ecotoxicology of fluoxetine. Toxicol Lett 142:169–183. https://doi.org/10.1016/s0378-4274(03)00066-3
Catel-Ferreira M, Marti S, Guillon L et al (2016) The outer membrane porin OmpW of Acinetobacter baumannii is involved in iron uptake and colistin binding. FEBS Lett 590:224–231. https://doi.org/10.1002/1873-3468.12050
Centers for disease control and prevention (2019) Antibiotic resistance threats in the United States 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report508.pdf. Accessed 15 October 2021
Clinical and Laboratory Standards Institute (2009) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard. In: CLSI Publication M7-A8, eighth ed. CLSI, Wayne
Dal T, Dal MS, Ağır I (2012) Acinetobacter baumannii’de antibiyotik direnci ve AdeABC aktif pompa sistemleri: Literatürün gözden geçirilmesi. Van Tıp Derg 19(3):137–148. https://jag.journalagent.com/vtd/pdfs/VTD_19_3_137_148.pdf.
De Sousa AK, Rocha JE, de Souza TG, de Freitas TS, Ribeiro-Filho J, Coutinho HDM (2018) New roles of fluoxetine in pharmacology: antibacterial effect and modulation of antibiotic activity. Microb Pathog 123:368–371. https://doi.org/10.1016/j.micpath.2018.07.040
Do TTT, Dao UPN, Bui HT, Nguyen TT (2017) Effect of electrostatic interaction between fluoxetine and lipid membranes on the partitioning of fluoxetine investigated using second derivative spectrophotometry and FTIR. Chem Phys Lipids 207:10–23. https://doi.org/10.1016/j.chemphyslip.2017.07.001
Eleaume H, Jabbouri S (2004) Comparison of two standardisation methods in real-time quantitative RT-PCR to follow Staphylococcus aureus genes expression during in vitro growth. J Microbiol Methods 59:363–370. https://doi.org/10.1016/j.mimet.2004.07.015
European Committee on Antimicrobial Susceptibility Testing (2018) Breakpoint tables for interpretation of MICs and zone diameters. Version 8.0, 2018. http://www.eucast.org. Accessed 15 August 2021
Jassim KA, Ghaima KK, Saadedin SMK (2016) AdeABC efflux pump genes in multidrug resistant Acinetobacter baumannii isolates. Avicenna J Clin Microbiol Infect. https://doi.org/10.17795/ajcmi-40898
Jin M, Lu J, Chen Z et al (2018) Antidepressant fluoxetine induces multiple antibiotics resistance in Escherichia coli via ROS mediated mutagenesis. Environ Int 120:421–430. https://doi.org/10.1016/j.envint.2018.07.046
Johnson DJ, Sanderson H, Brain RA et al (2007) Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae. Ecotoxicol Environ Saf 67(1):128–139. https://doi.org/10.1016/j.ecoenv.2006.03.016
Kart D, Gürpınar SS, Eryılmaz M (2020) Assessment of the anti-quorum sensing effect of Lactobacillus sp. metabolites on expression levels of QS-related genes in Pseudomonas aeruginosa PAO1. Turk Hij Deney Biyol Derg 77(3):311–318. https://doi.org/10.5505/TurkHijyen.2019.57873
Landers TF, Cohen B, Wittum TE, Larson EL (2012) A review of antibiotic use in food animals: perspective, policy, and potential. Public Health Rep 127(1):4–22. https://doi.org/10.1177/003335491212700103
Lari AR, Ardebili A, Hashemi A (2018) AdeR-AdeS mutations & overexpression of the AdeABC efflux system in ciprofloxacin-resistant Acinetobacter baumannii clinical isolates. Indian J Med Res 147:413–421. https://doi.org/10.4103/ijmr.IJMR_644_16
Laudy AE, Kulińska E, Tyski S (2017) The impact of efflux pump inhibitors on the activity of selected non-antibiotic medicinal products against gram-negative bacteria. Molecules 22(1):114. https://doi.org/10.3390/molecules22010114
Lopes BS (2012) Role of insertion sequences in the control of antibiotic resistance in Acinetobacter baumannii. Edinburgh University. Doctoral thesis.
Mastrianni KR, Lee LA, Brewer WE et al (2016) Variations in enzymatic hydrolysis efficiencies for amitriptyline and cyclobenzaprine in urine. J Anal Toxicol 40(9):732–737. https://doi.org/10.1093/jat/bkw062
McConnell MJ, Pérez-Ordóñez A, Pérez-Romero P et al (2012) Quantitative real-time PCR for detection of Acinetobacter baumannii colonization in the hospital environment. J Clin Microbiol 50(4):1412–1414. https://doi.org/10.1128/JCM.06566-11
Morehead MS, Scarbrough C (2018) Emergence of global antibiotic resistance. Prim Care 45:467–484. https://doi.org/10.1016/j.pop.2018.05.006
Munita JM, Arias CA (2016) Mechanisms of antibiotic resistance. Microbiol Spect. https://doi.org/10.1128/microbiolspec.VMBF-0016-2015
Munoz-Bellido JL, Munoz-Criado S, Garcia-Rodriguez JA (2000) Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors. Int J Antimicrob Agents 14(3):177–180. https://doi.org/10.1016/s0924-8579(99)00154-5
Şahin G, Giray B, Erkekoğlu P (2008) Trisiklik Antidepresanlar ile zehirlenmelerde tedavi yaklaşımları. Turkiye Klinikleri J Med Sci 28:533–543. http://www.eczaakademi.org/images/upld2/ecza_akademi/makale/20101027112044Bgiray_TCA.pdf
Sepahvand S, Davarpanah MA, Roudgari A et al (2017) Molecular evaluation of colistin-resistant gene expression changes in Acinetobacter baumannii with real-time polymerase chain reaction. Infect Drug Resist 10:455. https://doi.org/10.2147/IDR.S141196
Wang JH, Liu ZQ, Wang W et al (2001) Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther 70(1):42–47. https://doi.org/10.1067/mcp.2001.116513
Wieczorek P, Sacha P, Hauschild T et al (2008) Multidrug resistant Acinetobacter baumannii– the role of AdeABC (RND family) efflux pump in resistance to antibiotics. Folia Histochem Cytobiol 46(3):257–267. https://doi.org/10.2478/v10042-008-0056-x
World Health Organization (2020a) Antibiotic resistance. https://www.who.int/news-room/factsheets/detail/antibiotic-resistance. Accessed 23 August 2021
World Health Organization (2020b) Depression. https://www.who.int/news-room/factsheets/ detail/depression. Accessed 23 August 2021
Yang Z, Lu T, Zhu Y et al (2019) Aquatic ecotoxicity of an antidepressant, sertraline hydrochloride, onmicrobial communities. Sci Total Environ 654:129–134. https://doi.org/10.1016/j.scitotenv.2018.11.164
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This study was supported by the Scientific and Technological Research Council of Turkey [Grant number: TUBITAK-119S907].
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Ethical approval was received from Ethics Committee of Ankara University Faculty of Medicine [Reference No: I5-195-19].
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Communicated by Erko Stackebrandt.
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Gurpinar, S.S., Kart, D. & Eryilmaz, M. The effects of antidepressants fluoxetine, sertraline, and amitriptyline on the development of antibiotic resistance in Acinetobacter baumannii. Arch Microbiol 204, 230 (2022). https://doi.org/10.1007/s00203-022-02853-6
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DOI: https://doi.org/10.1007/s00203-022-02853-6