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Gallium activity against M. tuberculosis

Gallium is a metal that has been previously shown to inhibit the growth and kill M. tuberculosis in vitro. Gallium formulations are registered for use in humans for healthcare imaging and it is FDA approved. Recently, gallium compounds are included in several clinical trials as a potential drug to re-purpose for use in treatment of tuberculosis and non-tubercular mycobacteria.

The purpose of this study was to evaluate a combination of Gallium and such antituberculosis antibiotics as linezolid and levofloxacin against a multidrug resistant (MDR) M. tuberculosis strain resistant to rifampicin and isoniazid and to analyse the potential synergistic activity antibacterial compounds through metabolomics.

The work on this project has been possible through a tight collaboration within INNOVA4TB consortium: culturing of MDR M. tuberculosis strain was done at the SD Centre, Ukraine; Oleksandr Ilchenko, a PhD student of Odessa National University, Ukraine has conducted the largest part of this study supported by his advisers; metabolomic analysis was done at Umea University, Sweden; Cristina Prat, IGTP has been part of the project conceptualisation group together with Olena Rzhepishevska and colleagues from Umeå University.

 

We determined the minimal inhibitory concentration of gallium on the test strain in MGIT Bactec incubator. Further, sub-minimal inhibitory concentrations of gallium, linezolid and levofloxacin were used to determine the growth inhibition of M. tuberculosis based on time to detection value. Metabolites were extracted from cultures growing in presence of gallium, levofloxacin, linezolid, and their combinations.

Gas and liquid chromatography - mass spectrometry has been performed and multivariate analysis was used to analyse the results.

The results have been presented during INNOVA4TB webinars and research meetings, Metabolomics Conference 2022, Valencia, Spain (supported by INNOVA4TB conference participation grant) and UCMR Days Conference, Umea, Sweden.

Leading partners: UMU

Collaborating partners: ONU, SD Centre, IGTP, and UNIZAR

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