Ketamine used in the therapy of depressive disorders impacts protein profile, proliferation rate, and phagocytosis resistance of enterococci

Introduction A low concentration of ketamine is used to cause an anti-depressive effect. The mechanism of ketamine's action in depression is believed to result, among others, from its anti-inflammatory activity. Despite the fact that only high concentrations of ketamine inhibit bacterial growth, it is clear that even a sub-inhibitory concentration of chemicals may change bacterial properties. Considering the above, in the current study we aimed to evaluate the in vitro influence of ketamine on proliferation of enterococci and their interactions with monocytes. Materials and Methods The studied strains were isolated as etiological agents of infection at Medical University of Gdansk. The proliferation and metabolic activity were determined using the FACSVerse flow cytometer after addition of CFDA-SE to bacterial suspension. For the determination of phagocytosis resistance, THP-1 human monocytes cell line was used. Suspension of monocytes which engulfed CFDA-SE-stained bacteria was then stained with propidium iodide to evaluate cytotoxicity of enterococci. Results The result of the study showed unexpected response of bacterial cells to ketamine at an early stage of culture. In 57.7% of strains, both proliferation rate and metabolic activity were boosted. This group of strains was also less susceptible to phagocytosis than in culture without ketamine. Different response of isolates to ketamine was also visible in changes of proteins' profile determined by MALDI-TOF. Conclusions The analysis of bacteria at an early stage in the growth curve demonstrated the bacterial diversity in response to ketamine and let us set the hypothesis that microbiome susceptibility to ketamine may be one of the elements which should be taken into consideration when planning the successful pharmacotherapy of depression

Automated summary

This study evaluated the in vitro effects of low concentration ketamine on enterococci proliferation and their interactions with monocytes. The results showed that in the early stage of culture, 57.7% of enterococci strains had enhanced proliferation rate and metabolic activity when exposed to ketamine. These strains were also less susceptible to phagocytosis compared to cultures without ketamine. The response of isolates to ketamine was also evident in changes of protein profiles determined by MALDI-TOF.