LmrCD is a major multidrug resistance transporter in Lactococcus lactis
- 22 June 2006
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 61 (3), 771-781
- https://doi.org/10.1111/j.1365-2958.2006.05267.x
Abstract
When Lactococcus lactis is challenged with drugs it displays a multidrug resistance (MDR) phenotype. In silico analysis of the genome of L. lactis indicates the presence of at least 40 putative MDR transporters, of which only four, i.e. the ABC transporters LmrA, LmrC and LmrD, and the major facilitator LmrP, have been experimentally associated with the MDR. To understand the molecular basis of the MDR phenotype in L. lactis, we have performed a global transcriptome analysis comparing four independently isolated drug-resistant strains of L. lactis with the wild-type strain. The results show a strong and consistent upregulation of the lmrC and lmrD genes in all four strains, while the mRNA levels of other putative MDR transporters were not significantly altered. Deletion of lmrCD renders L. lactis sensitive to several toxic compounds, and this phenotype is associated with a reduced ability to secrete these compounds. Another gene, which is strongly upregulated in all mutant strains, specifies LmrR (YdaF), a local transcriptional repressor of lmrCD that belongs to the PadR family of transcriptional regulators and that binds to the promoter region of lmrCD. These results demonstrate that the heterodimeric MDR ABC transporter LmrCD is a major determinant of both acquired and intrinsic drug resistance of L. lactis.Keywords
This publication has 47 references indexed in Scilit:
- Nucleotide-Binding Sites of the Heterodimeric LmrCD ABC-Multidrug Transporter of Lactococcus lactis Are AsymmetricBiochemistry, 2005
- Use of an Efflux-Deficient Streptococcus pneumoniae Strain Panel To Identify ABC-Class Multidrug Transporters Involved in Intrinsic Resistance to Antimicrobial AgentsAntimicrobial Agents and Chemotherapy, 2005
- ydaG and ydbA of Lactococcus lactis Encode a Heterodimeric ATP-binding Cassette-type Multidrug TransporterPublished by Elsevier BV ,2004
- Characterization of YvcC (BmrA), a Multidrug ABC Transporter Constitutively Expressed in Bacillus subtilisBiochemistry, 2004
- Molecular Cloning and Characterization of an ABC Multidrug Efflux Pump, VcaM, in Non-O1 Vibrio choleraeAntimicrobial Agents and Chemotherapy, 2003
- Multidrug resistance in cancer: role of ATP–dependent transportersNature Reviews Cancer, 2002
- Phylogeny of multidrug transportersSeminars in Cell & Developmental Biology, 2001
- Microbial genome analyses: comparative transport capabilities in eighteen prokaryotesJournal of Molecular Biology, 2000
- Microbial genome analyses: global comparisons of transport capabilities based on phylogenies, bioenergetics and substrate specificitiesJournal of Molecular Biology, 1998
- A general system for generating unlabelled gene replacements in bacterial chromosomesMolecular Genetics and Genomics, 1996