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From ancestor to pathogen: Expansion and evolutionary adaptations of multidrug resistance causing MFS efflux pumps in mycobacteria.
Gene
December 2024
Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow 226025, UP, India. Electronic address:
Multidrug resistance (MDR) in Mycobacterium tuberculosis (Mtb) is a growing threat. Efflux pumps, particularly those belonging to the Major Facilitator Superfamily (MFS), play a key role in MDR. This study investigated MFS transporters across Mycobacterium spp.
View Article and Find Full Text PDFStructure and function of EfpA as a lipid transporter and its inhibition by BRD-8000.3.
Proc Natl Acad Sci U S A
October 2024
Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
EfpA, the first major facilitator superfamily (MFS) protein identified in (Mtb), is an essential efflux pump implicated in resistance to multiple drugs. EfpA-inhibitors have been developed to kill drug-tolerant Mtb. However, the biological function of EfpA has not yet been elucidated.
View Article and Find Full Text PDFDifferential Expression Analysis Reveals Possible New Quaternary Ammonium Compound Resistance Gene in Highly Resistant sp. HRI.
Microorganisms
September 2024
Department of Microbiology and Biochemistry, University of the Free State, Bloemfontein 9301, South Africa.
During the COVID-19 pandemic, the surge in disinfectant use emphasised their pivotal role in infection control. While the majority of antimicrobial resistance research focuses on antibiotics, resistance to biocides, which are present in disinfectants and sanitisers, is escalating. sp.
View Article and Find Full Text PDFStructure and inhibition mechanisms of essential transporter efflux protein A.
bioRxiv
September 2024
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
A broad chemical genetics screen in to identify inhibitors of established or previously untapped targets for therapeutic development yielded compounds (BRD-8000.3 and BRD-9327) that inhibit the essential efflux pump EfpA. To understand the mechanisms of inhibition by these compounds, we determined the structures of EfpA with inhibitors bound at 2.
View Article and Find Full Text PDFTranscriptomic and functional analyses on a Botrytis cinerea multidrug-resistant (MDR) strain provides new insights into the potential molecular mechanisms of MDR and fitness.
Mol Plant Pathol
September 2024
Department of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, Uppsala Biocenter, Uppsala, Sweden.
Botrytis cinerea is a notorious pathogen causing pre- and post-harvest spoilage in many economically important crops. Excessive application of site-specific fungicides to control the pathogen has led to the selection of strains possessing target site alterations associated with resistance to these fungicides and/or strains overexpressing efflux transporters associated with multidrug resistance (MDR). MDR in B.
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