Expression of <i>Plasmodium</i> major facilitator superfamily protein in transporters – Δ <i>Candida</i> identifies a drug transporter
<b>Aim:</b> To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; '<i>Pf</i>MFSDT') as a drug transporter, using <i>Candida glabrata</i> for orthologous protein expression.<b>Methods:</b> Complementary Determining Sequence encoding <i>Pf</i>MFSDT was integrated into the genome of genetically engineered <i>C. glabrata</i> strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter.<b>Results & conclusion:</b> The modified <i>C. glabrata</i> strain exhibited plasma membrane localization of <i>Pf</i>MFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole. The nanomolar inhibitory effects of the drugs on the intra-erythrocytic growth of <i>Plasmodium falciparum</i> highlight their antimalarial properties. This study proposes <i>Pf</i>MFSDT as a drug transporter, expanding the repertoire of the currently known antimalarial 'resistome'.
Authors
- Preeti Maurya (ORCID: https://orcid.org/0009-0005-2462-9334)
- Christoph Arenz (ORCID: https://orcid.org/0000-0001-7613-9437)
- Shailja Singh (ORCID: https://orcid.org/0000-0001-5286-6605)
- Aashima Gupta (ORCID: https://orcid.org/0000-0003-4302-3731)
- Harshita Singh (ORCID: https://orcid.org/0000-0002-3124-5348)
- Haider Thaer Abdulhameed Almuqdadi (ORCID: https://orcid.org/0009-0008-3743-7480)
- Ravi Jain (ORCID: https://orcid.org/0000-0001-7844-1031)
- Naseem A. Gaur (ORCID: https://orcid.org/0000-0002-1224-8789)
- Mohit Kumar
Institutions
- Jawaharlal Nehru University (IN)
- Humboldt-Universität zu Berlin (DE)
- International Centre for Genetic Engineering and Biotechnology (IN)
- Nahrain University (IQ)
- Jamia Millia Islamia (IN)
Publication Details
- Journal
- Future Microbiology
- Published
- 2024-09-05
- DOI
- https://doi.org/10.1080/17460913.2024.2389750
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Department of Biotechnology, Ministry of Science and Technology, India