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Status |
Public on Jun 10, 2024 |
Title |
The cyclic-AMP binding domain of the efflux pump Rv3728 acts as a regulator of phosphatidyl-myo-inositol mannosides composition in Mycobacterium tuberculosis |
Organism |
Mycobacterium tuberculosis H37Rv |
Experiment type |
Genome variation profiling by high throughput sequencing
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Summary |
Tuberculosis (TB) is an ancient disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). The rise of antimicrobial resistance (AMR) threatens to bring Mtb to the forefront of bacterial pathogens as the current treatments are increasingly becoming ineffective. Understanding the development of AMR and the virulence processes of Mtb is crucial for the identification of new drug targets and the rational design of anti-TB treatments. One of the established mechanisms of resistance is through the function of efflux proteins, which are transmembrane transporters that bind and remove antibiotic molecules out from the cell. Here, we determine the role of Rv3728, a major facilitator superfamily (MFS) efflux pump protein, which also predicted to bind 3',5'-cyclic adenosine monophosphate (cAMP). Using bioinformatic tools and cAMP binding assay, we confirm that Rv3728 binds to cAMP and identified E597 and R606 as important residues involved in binding. Although Rv3728 deletion has no impact on bacterial resistance and tolerance to different antibiotics, it affects membrane permeability and alters the acylation profile of phosphatidyl-myo-inositol mannosides lipids.
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Overall design |
Mycobacterium tuberculosis H37Rv KO and WT.
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Contributor(s) |
Larrouy-Maumus G, Tounta V, Chakraborty M, Liu Y, Fernandes N, Williams R, Meier T, Vaubourgeix J, Botella H, Visweswariah SS |
Citation missing |
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Submission date |
Jun 03, 2024 |
Last update date |
Jun 10, 2024 |
Contact name |
Gerald J Larrouy-Maumus |
Organization name |
Imperial College London
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Street address |
South Kensington Campus
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City |
London |
ZIP/Postal code |
SW7 2AZ |
Country |
United Kingdom |
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Platforms (1) |
GPL34550 |
NextSeq 2000 (Mycobacterium tuberculosis H37Rv) |
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Samples (5)
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Relations |
BioProject |
PRJNA1119542 |