Mutants of the Bacillus subtilis multidrug transporter Bmr with altered sensitivity to the antihypertensive alkaloid reserpine - PubMed (original) (raw)
. 1993 May 25;268(15):11086-9.
Affiliations
- PMID: 8098708
Free article
Mutants of the Bacillus subtilis multidrug transporter Bmr with altered sensitivity to the antihypertensive alkaloid reserpine
M Ahmed et al. J Biol Chem. 1993.
Free article
Abstract
The Bacillus subtilis multidrug transporter Bmr effluxes structurally diverse toxic compounds out of bacterial cells. Antihypertensive alkaloid reserpine reverses Bmr-mediated multidrug resistance by inhibiting drug transport. We have obtained a mutant of the bmr gene that provides a normal level of multidrug resistance, which can, however, only be reversed by very high concentrations of reserpine. Reduction of Bmr sensitivity to reserpine has been caused by the substitution of Leu for Val286 in the Bmr molecule. This mutation also led to a dramatic decrease of [3H]reserpine binding to membrane vesicles prepared from the Bmr-overexpressing bacteria. Leucine is larger than valine by one methylene group. Substitution of Val286 with a smaller residue, glycine, had an opposite effect. It led to increased sensitivity of Bmr to reserpine and increased affinity of reserpine binding to the membranes prepared from Bmr-overexpressing bacteria. Neither of the mutations significantly changed the sensitivity of Bmr to rescinnamine, a structural analog of reserpine. The results suggest that Val286 is involved in the formation of the reserpine-binding site of the Bmr molecule.
Similar articles
- Mutations affecting substrate specificity of the Bacillus subtilis multidrug transporter Bmr.
Klyachko KA, Schuldiner S, Neyfakh AA. Klyachko KA, et al. J Bacteriol. 1997 Apr;179(7):2189-93. doi: 10.1128/jb.179.7.2189-2193.1997. J Bacteriol. 1997. PMID: 9079903 Free PMC article. - Two highly similar multidrug transporters of Bacillus subtilis whose expression is differentially regulated.
Ahmed M, Lyass L, Markham PN, Taylor SS, Vázquez-Laslop N, Neyfakh AA. Ahmed M, et al. J Bacteriol. 1995 Jul;177(14):3904-10. doi: 10.1128/jb.177.14.3904-3910.1995. J Bacteriol. 1995. PMID: 7608059 Free PMC article. - The multidrug efflux transporter of Bacillus subtilis is a structural and functional homolog of the Staphylococcus NorA protein.
Neyfakh AA. Neyfakh AA. Antimicrob Agents Chemother. 1992 Feb;36(2):484-5. doi: 10.1128/AAC.36.2.484. Antimicrob Agents Chemother. 1992. PMID: 1605617 Free PMC article. - Prokaryote multidrug efflux proteins of the major facilitator superfamily: amplified expression, purification and characterisation.
Ward A, Hoyle C, Palmer S, O'Reilly J, Griffith J, Pos M, Morrison S, Poolman B, Gwynne M, Henderson P. Ward A, et al. J Mol Microbiol Biotechnol. 2001 Apr;3(2):193-200. J Mol Microbiol Biotechnol. 2001. PMID: 11321573 Review. - The ostensible paradox of multidrug recognition.
Neyfakh AA. Neyfakh AA. J Mol Microbiol Biotechnol. 2001 Apr;3(2):151-4. J Mol Microbiol Biotechnol. 2001. PMID: 11321567 Review.
Cited by
- Penetration of Triphenylphosphonium Derivatives through the Cell Envelope of Bacteria of Mycobacteriales Order.
Nazarov PA, Majorov KB, Apt AS, Skulachev MV. Nazarov PA, et al. Pharmaceuticals (Basel). 2023 May 2;16(5):688. doi: 10.3390/ph16050688. Pharmaceuticals (Basel). 2023. PMID: 37242470 Free PMC article. - Novel antimicrobial strategies to treat multi-drug resistant Staphylococcus aureus infections.
Douglas EJA, Wulandari SW, Lovell SD, Laabei M. Douglas EJA, et al. Microb Biotechnol. 2023 Jul;16(7):1456-1474. doi: 10.1111/1751-7915.14268. Epub 2023 May 13. Microb Biotechnol. 2023. PMID: 37178319 Free PMC article. Review. - Evaluation of efflux pump inhibitory activity of some plant extracts and using them as adjuvants to potentiate the inhibitory activity of some antibiotics against Staphylococcus aureus.
Al-Sallami D, Alsultan A, Abbas KH, Clarke SR. Al-Sallami D, et al. Open Vet J. 2023 Jan;13(1):42-47. doi: 10.5455/OVJ.2023.v13.i1.5. Epub 2023 Jan 9. Open Vet J. 2023. PMID: 36777436 Free PMC article. - Biosynthesis Investigations of Terpenoid, Alkaloid, and Flavonoid Antimicrobial Agents Derived from Medicinal Plants.
Huang W, Wang Y, Tian W, Cui X, Tu P, Li J, Shi S, Liu X. Huang W, et al. Antibiotics (Basel). 2022 Oct 9;11(10):1380. doi: 10.3390/antibiotics11101380. Antibiotics (Basel). 2022. PMID: 36290037 Free PMC article. Review. - Critical discussion on drug efflux in Mycobacterium tuberculosis.
Remm S, Earp JC, Dick T, Dartois V, Seeger MA. Remm S, et al. FEMS Microbiol Rev. 2022 Feb 9;46(1):fuab050. doi: 10.1093/femsre/fuab050. FEMS Microbiol Rev. 2022. PMID: 34637511 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases