Antidepressant drug against bacterial pathogens: Effect of citalopram on biofilm forming hospital-acquired infectious (HAIs) agents

The development of multidrug resistance in bacterial pathogens in many ways including by the formation of biofilms has been considered as one of the major challenges that human beings face. As the biofilms form complex structures that help the bacteria to evade the host defense mechanisms resulting in serious socio-economic implications due to longer morbidity and higher mortality, there is an urgent need for new antimicrobial compounds with promising mechanisms of action. Drug repurposing is a novel method to find out the antibacterial activities of well-defined drugs in use, and here, citalopram, an antidepressant that comes under the SSRI category was investigated for its potential against three of the major hospitalacquired infection-causing bacteria, viz., Enterococcus faecalis, Escherichia coli and Staphylococcus aureus. In the present study, analyses were performed for the antimicrobial activities by well-diffusion protocols, for the minimal inhibitory concentrations (MICs) by microdilution method, the effect of the drug on pre-formed and mature biofilms by crystal violet method, synergic effects of the drug and selected antibiotics on the bacterial pathogens by checkerboard assay, etc., using standard protocols. The drug citalopram displayed potential activities against all of the selected bacterial pathogens and its MICs were found to be 62.5 mu g/ml against E. faecalis, 125 mu g/ml each against S. aureus and E. coli. The drug also showed remarkable antibiofilm activities and, at MIC levels, the eradication was 96.3%, 82% and 89% of mature biofilms by S. aureus, E. coli and E. faecalis. When combined with ampicillin and rifampicin, the drug citalopram displayed enhanced synergic effects against the pathogens. The drug was found to possess promising antibacterial and antibiofilm activities against three of the major hospital-acquired infections causing microbial pathogenic organisms, viz., E. faecalis, S. aureus, and E. coli. As the drug exhibited enhanced activities when combined with commercially available antibiotics, further studies could be conducted for a repurposed use of citalopram as an antibiotic.