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Multidrug and efflux transporters of the model microbe Dictyostelium discoideum

Multidrug and efflux transporters of the model microbe Dictyostelium discoideum

Ferrara, Bill T., Saleh, Salma Mounir and Thompson, Elinor ORCID: 0000-0002-6434-9290 (2020) Multidrug and efflux transporters of the model microbe Dictyostelium discoideum. In: Access Microbiology. Microbiology Society, London, UK. ISSN 2516-8290 (Online) (doi:https://doi.org/10.1099/acmi.ac2020.po0194)

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Abstract

The evolutionarily ubiquitous multidrug and toxin efflux (MATE) proteins mediate anticancer and antibiotic resistance, while transporting toxins, ions and flavonoids in plants. MATEs of the model amoeba Dictyostelium discoideumhave not been studied although sequences of its pair group with the two Homo sapiens MATEs. Ddmate1 and 2 are both transcribed, Ddmate2 more so, with peaks in vegetative and slug life-cycle stages. Ddmate1 was upregulated in response to a toxin, ethidium bromide, at the lowest concentration tested. Removing MATE function by inhibitor or mutation increased intracellular levels of various compounds, confirming these as efflux transporters. Plasma membrane localisation was revealed using a GFP-MATE1 reporter-line. MATE1 and MATE2 phenotypes indicated roles beyond detoxification: on Klebsiella lawns these mutants produced significantly smaller plaques than WT, and their axenic growth rates were also lower. The transporters’ impact on use of Dictyostelium for novel drug research was tested using flavonoids. LCMS and fluorescence-imaging revealed differential flavonoid uptake. Flavanones such as naringenin did not cross into cells, whereas flavonols localised to mitochondria and cytoplasm. Ddmate1transcription was upregulated, however, in response to naringenin, which is known to reduce levels of kidney-disease protein PKD2 in both Dictyostelium and animal cells. Increased flavonol intracellular concentrations confirmed that efflux not import was impeded in MATE1andMATE2, and kaempferol therefore further reduced MATE1-cells’ growth. These D. discoideum MATEs may usefully model the HsMATEs, aid understanding of flavonoids’ effects, and should be considered when using this model eukaryote to screen drugs.

Item Type: Conference Proceedings
Title of Proceedings: Access Microbiology
Uncontrolled Keywords: MATE transporter, efflux, dictyostelium, flavonoid
Subjects: Q Science > QH Natural history > QH301 Biology
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Biology & Biotechnology Research Group
Faculty of Engineering & Science > School of Science (SCI)
Last Modified: 18 Aug 2020 13:11
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None
Selected for REF2021: None
URI: http://gala.gre.ac.uk/id/eprint/28318

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