Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factors.

Abstract:

:The increase in bacterial resistance to multiple drugs represents a serious and growing health risk. One component of multidrug resistance (MDR) is a group of multidrug transporters that are often regulated at the transcriptional level by repressors and/or activators. Some of these transcription factors are also multidrug-binding proteins, frequently recognizing the same array of drugs that are effluxed by the transporters that they regulate. How a single protein can recognize such chemically disparate compounds is an intriguing question from a structural standpoint and an important question in future drug development endeavours. Unlike the multidrug transporters, the cytosolic multidrug-binding regulatory proteins are more tractable systems for structural analyses. Here, we describe recent crystallographic studies on MarR, BmrR and QacR, three bacterial transcription regulators that are also multidrug-binding proteins. Although our understanding of multidrug binding and transcriptional regulation by MarR is in its initial stages, the structure of a BmrR-TPP+-DNA complex has revealed important insights into the novel transcription activation mechanism of the MerR family, and the structures of a QacR-DNA complex and QacR bound to six different drugs have revealed not only the mechanism of induction of this repressor but has afforded the first view of any MDR protein bound to multiple drugs.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Schumacher MA,Brennan RG

doi

10.1046/j.1365-2958.2002.03039.x

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

885-93

issue

4

eissn

0950-382X

issn

1365-2958

pii

3039

journal_volume

45

pub_type

杂志文章,评审
  • Cloning, characterization and disruption of a (p)ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2).

    abstract::An internal segment of the (p)ppGpp synthetase gene, relA, of Streptomyces coelicolor A3(2) was amplified from genomic DNA using the polymerase chain reaction and used as a hybridization probe to isolate the complete gene from a cosmid library. relA lies downstream of a gene (apt) that apparently encodes adenine phosp...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1996.390919.x

    authors: Chakraburtty R,White J,Takano E,Bibb M

    更新日期:1996-01-01 00:00:00

  • Magnesium depletion triggers production of an immune modulating diterpenoid in Mycobacterium tuberculosis.

    abstract::Mycobacterium tuberculosis (Mtb) is the causative agent of the human disease Tuberculosis, and remains a worldwide health threat responsible for ∼1.7 million deaths annually. During infection, Mtb prevents acidification of the engulfing phagosome, thus blocking endocytic progression and eventually leading to stable re...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2011.07545.x

    authors: Mann FM,VanderVen BC,Peters RJ

    更新日期:2011-03-01 00:00:00

  • Nucleoid-associated PhaF phasin drives intracellular location and segregation of polyhydroxyalkanoate granules in Pseudomonas putida KT2442.

    abstract::The PhaF is a nucleoid-associated like protein of Pseudomonas putida KT2442 involved in the polyhydroxyalkanoate (PHA) metabolism. Its primary structure shows two modular domains; the N-terminal PHA granule-binding domain (phasin domain) and the C-terminal half containing AAKP-like tandem repeats characteristic of the...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07450.x

    authors: Galán B,Dinjaski N,Maestro B,de Eugenio LI,Escapa IF,Sanz JM,García JL,Prieto MA

    更新日期:2011-01-01 00:00:00

  • The unusual mycobacterial chaperonins: evidence for in vivo oligomerization and specialization of function.

    abstract::The pathogen Mycobacterium tuberculosis expresses two chaperonins, one (Cpn60.1) dispensable and one (Cpn60.2) essential. These proteins have been reported not to form oligomers despite the fact that oligomerization of chaperonins is regarded as essential for their function. We show here that the Cpn60.2 homologue fro...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2012.08150.x

    authors: Fan M,Rao T,Zacco E,Ahmed MT,Shukla A,Ojha A,Freeke J,Robinson CV,Benesch JL,Lund PA

    更新日期:2012-09-01 00:00:00

  • Generation of the heterodimeric precursor GP3 of the Chlamydomonas cell wall.

    abstract::The cell wall of the unicellular green alga Chlamydomonas reinhardtii exclusively consists of hydroxyproline-containing glycoproteins. Protein chemical analysis of its polypeptide constituents was hindered by their cross-linking via peroxidase-catalysed intermolecular isodityrosine formation and transaminase-dependent...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07302.x

    authors: Voigt J,Kiess M,Getzlaff R,Wöstemeyer J,Frank R

    更新日期:2010-09-01 00:00:00

  • Identification of competence pheromone responsive genes in Streptococcus pneumoniae by use of DNA microarrays.

    abstract::Natural genetic transformation in Streptococcus pneumoniae is controlled in part by a quorum-sensing system mediated by a peptide pheromone called competence-stimulating peptide (CSP), which acts to coordinate transient activation of genes required for competence. To characterize the transcriptional response and regul...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03907.x

    authors: Peterson SN,Sung CK,Cline R,Desai BV,Snesrud EC,Luo P,Walling J,Li H,Mintz M,Tsegaye G,Burr PC,Do Y,Ahn S,Gilbert J,Fleischmann RD,Morrison DA

    更新日期:2004-02-01 00:00:00

  • The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation.

    abstract::Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains. These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination. Tr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb01014.x

    authors: Suker J,Feavers IM,Achtman M,Morelli G,Wang JF,Maiden MC

    更新日期:1994-04-01 00:00:00

  • A secondary RNA polymerase sigma factor from Streptococcus pyogenes.

    abstract::The important human pathogen Streptococcus pyogenes (the group A streptococcus or GAS) causes diseases ranging from mild, self-limiting pharyngitis to severe invasive infections. Regulation of the expression of GAS genes in response to specific environmental differences within the host is probably key in determining t...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02657.x

    authors: Opdyke JA,Scott JR,Moran CP Jr

    更新日期:2001-10-01 00:00:00

  • Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor.

    abstract::Staphylococcus aureus is a leading cause of infective endocarditis (IE). Platelet activation promoted by S. aureus resulting in aggregation and thrombus formation is an important step in the pathogenesis of IE. Here, we report that the fibrinogen/fibronectin-binding proteins FnBPA and FnBPB are major platelet-activati...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04922.x

    authors: Fitzgerald JR,Loughman A,Keane F,Brennan M,Knobel M,Higgins J,Visai L,Speziale P,Cox D,Foster TJ

    更新日期:2006-01-01 00:00:00

  • Genetic instability of the Streptomyces chromosome.

    abstract::The Streptomyces wild-type chromosome is linear in all examples studied. The ends of the chromosome or telomeres consist of terminal inverted repeats of various sizes with proteins covalently bound to their 5' ends. The chromosome is very unstable and undergoes very large deletions spontaneously at rates higher than 0...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2958.1998.00652.x

    authors: Volff JN,Altenbuchner J

    更新日期:1998-01-01 00:00:00

  • A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp.

    abstract::Roughly 10% of all genes in Escherichia coli are controlled by the global transcription factor Lrp, which responds to nutrient availability. Bioinformatically, we identified lrp as one of several putative targets for the sRNA MicF, which is transcriptionally downregulated by Lrp. Deleting micF results in higher Lrp le...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2012.07994.x

    authors: Holmqvist E,Unoson C,Reimegård J,Wagner EG

    更新日期:2012-05-01 00:00:00

  • Genetic characterization of a Rhizobium meliloti lactose utilization locus.

    abstract::We identified several linked genes of a lactose regulon in Rhizobium meliloti. These were lacZ, the structural gene for beta-galactosidase; lacR, the lactose repressor gene; and two genes encoding proteins of unknown function, lacW and lacX. Insertion mutants in lacW and lacZ belonged to a single genetic complementati...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb00298.x

    authors: Jelesko JG,Leigh JA

    更新日期:1994-01-01 00:00:00

  • The transferrin-iron import system from pathogenic Neisseria species.

    abstract::Two pathogenic species within the genus Neisseria cause the diseases gonorrhoea and meningitis. While vaccines are available to protect against four N. meningitidis serogroups, there is currently no commercial vaccine to protect against serogroup B or against N. gonorrhoeae. Moreover, the available vaccines have signi...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/mmi.12002

    authors: Noinaj N,Buchanan SK,Cornelissen CN

    更新日期:2012-10-01 00:00:00

  • Differential fiu-lacZ fusion regulation linked to Escherichia coli colony development.

    abstract::Colonies of strains carrying a stable lambdaplacMu15 translational fusion displayed sharply defined intense staining at the centre on Xgal medium. The fusion was in fiu (ferric ion uptake), encoding an iron-regulated outer membrane protein (IROMP) controlled via four overlapping ferric uptake regulator (Fur) boxes in ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01423.x

    authors: Newman DL,Shapiro JA

    更新日期:1999-07-01 00:00:00

  • Variations in the surface proteins and restriction enzyme systems of Mycoplasma pulmonis in the respiratory tract of infected rats.

    abstract::Restriction and modification (R-M) systems are generally thought to protect bacteria from invasion by foreign DNA. This paper proposes the existence of an alternative role for the phase-variable R-M systems encoded by the hsd loci of Mycoplasma pulmonis. Populations of M. pulmonis cells that arose during growth in dif...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02464.x

    authors: Gumulak-Smith J,Teachman A,Tu AH,Simecka JW,Lindsey JR,Dybvig K

    更新日期:2001-05-01 00:00:00

  • An RNA trap helps bacteria get the most out of chitosugars.

    abstract::Small regulatory RNAs (sRNAs) are well known to command bacterial protein synthesis by modulating the translation and decay of target mRNAs. Most sRNAs are specifically regulated by a cognate transcription factor under certain growth or stress conditions. Investigations of the conserved Hfq-dependent MicM sRNA in Esch...

    journal_title:Molecular microbiology

    pub_type: 评论,杂志文章

    doi:10.1111/j.1365-2958.2009.06806.x

    authors: Vogel J

    更新日期:2009-09-01 00:00:00

  • Identification of novel virulence factors associated with signal transduction pathways in Alternaria brassicicola.

    abstract::Alternaria brassicicola is an important, necrotrophic fungal pathogen that causes black spot disease on Brassicas. In order to study pathogenicity mechanisms, gene deletion mutants were generated for 21 putative regulatory genes including kinases and transcription factors subjectively selected from the annotated A. br...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06689.x

    authors: Cho Y,Kim KH,La Rota M,Scott D,Santopietro G,Callihan M,Mitchell TK,Lawrence CB

    更新日期:2009-06-01 00:00:00

  • BrgE is a regulator of Myxococcus xanthus development.

    abstract::We report here the identification and characterization of a member of the Myxococcus xanthus SdeK signal transduction pathway, BrgE. This protein was identified as an SdeK-interacting component using a yeast two-hybrid screen, and we further confirmed this interaction by the glutathione S-transferase (GST) pulldown as...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04726.x

    authors: Pham VD,Shebelut CW,Zumstein EJ,Singer M

    更新日期:2005-08-01 00:00:00

  • Action of receiver and activator modules of UhpA in transcriptional control of the Escherichia coli sugar phosphate transport system.

    abstract::Induction of the sugar-phosphate transport system in Escherichia coli by external glucose-6-phosphate is regulated by the UhpABC regulatory proteins. UhpA protein is required for uhpT transcription and is related to response regulators of two-component regulatory systems. UhpA and its homologues appear to be composed ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.tb02358.x

    authors: Webber CA,Kadner RJ

    更新日期:1995-03-01 00:00:00

  • Differential mRNA stability of the cspA gene in the cold-shock response of Escherichia coli.

    abstract::Exposure of bacterial cells to temperature changes induces the synthesis of a set proteins. We investigated the control of expression of the cspA gene, coding for the major cold-shock protein of Escherichia coli. This protein was shown to be transiently induced upon shift to low temperature. We demonstrated that the c...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1996.363898.x

    authors: Goldenberg D,Azar I,Oppenheim AB

    更新日期:1996-01-01 00:00:00

  • Soluble sugar permeases of the phosphotransferase system in Escherichia coli: evidence for two physically distinct forms of the proteins in vivo.

    abstract::The bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS) consists of a set of cytoplasmic energy-coupling proteins and various integral membrane permeases/sugar phosphotransferases, each specific for a different sugar. We have conducted biochemical analyses of three PTS permeases (enzymes II), the g...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03394.x

    authors: Aboulwafa M,Saier M Jr

    更新日期:2003-04-01 00:00:00

  • The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signalling pathway.

    abstract::In the intracellular pathogen Brucella abortus, the general stress response (GSR) signalling system determines survival under acute stress conditions in vitro, and is required for long-term residence in a mammalian host. To date, the identity of the Brucella sensor kinase(s) that function to perceive stress and direct...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12809

    authors: Kim HS,Willett JW,Jain-Gupta N,Fiebig A,Crosson S

    更新日期:2014-11-01 00:00:00

  • The involvement of NAD(P)H dehydrogenase subunits, NdhD3 and NdhF3, in high-affinity CO2 uptake in Synechococcus sp. PCC7002 gives evidence for multiple NDH-1 complexes with specific roles in cyanobacteria.

    abstract::Random gene tagging was used to obtain new mutants of the marine cyanobacterium, Synechococcus sp. PCC7002, with defects in the CO2-concentrating mechanism (CCM). Two of these mutants, K22 and A41, showed poor growth at limiting CO2. Isolation and sequencing of a 6. 6 kb genomic region revealed the existence of five p...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01457.x

    authors: Klughammer B,Sültemeyer D,Badger MR,Price GD

    更新日期:1999-06-01 00:00:00

  • Visualization of the subcellular location of sporulation proteins in Bacillus subtilis using immunofluorescence microscopy.

    abstract::We describe the application of immunofluorescence microscopy to visualization of the subcellular localization of proteins involved in coat morphogenesis and chromosome packaging during the process of sporulation in Bacillus subtilis. In confirmation and extension of previous findings, we show that SpolVA, which is res...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.mmi_18030459.x

    authors: Pogliano K,Harry E,Losick R

    更新日期:1995-11-01 00:00:00

  • CooB is required for assembly but not transport of CS1 pilin.

    abstract::CS1 pili are filamentous proteinaceous appendages found on many enterotoxigenic Escherichia coli (ETEC) strains isolated from human diarrhoeal disease. They are thought to effect colonization of the upper intestine by facilitating binding to human ileal epithelial cells. We have identified a gene, cooB, which lies dir...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01471.x

    authors: Scott JR,Wakefield JC,Russell PW,Orndorff PE,Froehlich BJ

    更新日期:1992-02-01 00:00:00

  • Live cell imaging of SOS and prophage dynamics in isogenic bacterial populations.

    abstract::Almost all bacterial genomes contain DNA of viral origin, including functional prophages or degenerated phage elements. A frequent but often unnoted phenomenon is the spontaneous induction of prophage elements (SPI) even in the absence of an external stimulus. In this study, we have analyzed SPI of the large, degenera...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13147

    authors: Helfrich S,Pfeifer E,Krämer C,Sachs CC,Wiechert W,Kohlheyer D,Nöh K,Frunzke J

    更新日期:2015-11-01 00:00:00

  • The complete nucleotide sequence of the Pasteurella multocida toxin gene and evidence for a transcriptional repressor, TxaR.

    abstract::The osteolytic toxin of Pasteurella multocida induces bone resorption in vivo and in vitro (Foged et al., 1988; Kimman et al., 1987). In this report the toxin-encoding toxA gene is sequenced, and the deduced primary structure of the toxin shows a protein of 1285 amino acids, containing a striking homology to a metal-b...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1990.tb00652.x

    authors: Petersen SK

    更新日期:1990-05-01 00:00:00

  • Rcs signalling-activated transcription of rcsA induces strong anti-sense transcription of upstream fliPQR flagellar genes from a weak intergenic promoter: regulatory roles for the anti-sense transcript in virulence and motility.

    abstract::In Salmonella enterica, an activated Rcs signalling system inhibits initiation of transcription of the flhD master operon. Under these conditions, where motility is shut down, microarray experiments showed an increased RNA signal for three flagellar genes -fliPQR- located upstream of rcsA. We show here that it is the ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06851.x

    authors: Wang Q,Harshey RM

    更新日期:2009-10-01 00:00:00

  • A role for the FtsQLB complex in cytokinetic ring activation revealed by an ftsL allele that accelerates division.

    abstract::The cytokinetic apparatus of bacteria is initially formed by the polymerization of the tubulin-like FtsZ protein into a ring structure at midcell. This so-called Z-ring facilitates the recruitment of many additional proteins to the division site to form the mature divisome machine. Although the assembly pathway leadin...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12905

    authors: Tsang MJ,Bernhardt TG

    更新日期:2015-03-01 00:00:00

  • The large subunit of Leishmania topoisomerase I functions as the 'molecular steer' in type IB topoisomerase.

    abstract::Kinetoplastid topoisomerase IB is an unusual bisubunit enzyme where reconstitution of the large (LdTOPIL or L) and small (LdTOPIS or S) subunits shows functional activity. It is yet to be deciphered whether one subunit or both navigate the heterodimer to its cellular DNA targets. Tethering a specific DNA-binding prote...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.06002.x

    authors: BoseDasgupta S,Ganguly A,Das BB,Roy A,Khalkho NV,Majumder HK

    更新日期:2008-01-01 00:00:00