MexAB-OprM hyperexpression in NalC-type multidrug-resistant Pseudomonas aeruginosa: identification and characterization of the nalC gene encoding a repressor of PA3720-PA3719.


:MexAB-OprM is a multidrug efflux system that contributes to intrinsic and acquired multidrug resistance in Pseudomonas aeruginosa, the latter as a result of mutational hyperexpression of the mexAB-oprM operon. While efflux gene hyperexpression typically results from mutations in the linked mexR repressor gene, it also occurs independently of mexR mutations in so-called nalC mutants that demonstrate more modest mexAB-oprM expression and, thus, more modest multidrug resistance than do mexR strains. Using a transposon insertion mutagenesis approach, nalC mutant strains were selected and the disrupted gene, PA3721, identified. Amplification and sequencing of this gene from previously isolated spontaneous nalC mutants revealed the presence of mutations in all instances and as such, PA3721 has been renamed nalC. PA3721 (nalC) encodes a probable repressor of the TetR/AcrR family and occurs upstream of an apparent two-gene operon, PA3720-PA3719, whose expression was negatively regulated by PA3721. Thus, PA3720-PA3719 was hyperexpressed in transposon insertion and spontaneous nalC mutants. The loss of PA3719 but not of PA3720 expression in a spontaneous nalC mutant reduced MexAB-OprM expression to wild-type levels and compromised multidrug resistance, an indication that hyperexpression of PA3719 only was necessary for the nalC phenotype. Introduction of PA3719 into wild-type P. aeruginosa on a multicopy plasmid was, in fact, sufficient to promote elevated MexAB-OprM expression and multidrug resistance characteristic of a nalC strain. Thus, the nalC (PA3721) mutation serves only to enhance PA3720-PA3719 expression, with expression of PA3719 (encodes a 53 amino acid protein of predicted pI 10.4) directly or indirectly impacting MexAB-OprM expression. Intriguingly, nalC strains produce markedly elevated levels of stable MexR protein suggesting that PA3720-PA3719 hyperexpression somehow modulates MexR repressor activity. The deduced products of PA3720-PA3719 show no homology to sequences presently in the GenBank databases, however, and as such provide no clues as to how this might occur.


Mol Microbiol


Molecular microbiology


Cao L,Srikumar R,Poole K




Has Abstract


2004-09-01 00:00:00














  • PhoP/PhoQ: macrophage-specific modulators of Salmonella virulence?

    abstract::The regulation of gene expression by the two-component regulatory system PhoP/PhoQ is necessary for Salmonella typhimurium survival within macrophages, defensin resistance, acid resistance, and murine typhoid fever pathogenesis. Salmonella experience multiple environments during mammalian infection and survival requir...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审


    authors: Miller SI

    更新日期:1991-09-01 00:00:00

  • A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern.

    abstract::The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Kyes SA,Christodoulou Z,Raza A,Horrocks P,Pinches R,Rowe JA,Newbold CI

    更新日期:2003-06-01 00:00:00

  • A co-activator of nitrogen-regulated transcription in Saccharomyces cerevisiae.

    abstract::In Saccharomyces cerevisiae, the transcription factors Gln3p and Nil1p of the GATA family play a determinant role in expression of genes that are subject to nitrogen catabolite repression. Here we report the isolation of a new yeast mutant, gan1-1, exhibiting dramatically decreased NAD-linked glutamate dehydrogenase (...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Soussi-Boudekou S,André B

    更新日期:1999-02-01 00:00:00

  • The transcription of bradyzoite genes in Toxoplasma gondii is controlled by autonomous promoter elements.

    abstract::Experimental evidence suggests that apicomplexan parasites possess bipartite promoters with basal and regulated cis-elements similar to other eukaryotes. Using a dual luciferase model adapted for recombinational cloning and use in Toxoplasma gondii, we show that genomic regions flanking 16 parasite genes, which encomp...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Behnke MS,Radke JB,Smith AT,Sullivan WJ Jr,White MW

    更新日期:2008-06-01 00:00:00

  • The pYV plasmid of Yersinia encodes a lipoprotein, YlpA, related to TraT.

    abstract::A series of lipoproteins was detected in the membrane fraction of Yersinia enterocolitica W227, a typical strain from serotype O:9. At least two of them, YlpA and YlpB, are encoded by the pYV plasmid. The sequence of ylpA reveals the presence of a typical lipoprotein signal peptide. The mature YlpA protein would be 22...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: China B,Michiels T,Cornelis GR

    更新日期:1990-09-01 00:00:00

  • Cellobiohydrolase A (CbhA) from the cellulolytic bacterium Cellulomonas fimi is a beta-1,4-exocellobiohydrolase analogous to Trichoderma reesei CBH II.

    abstract::The gene cbhA from the cellulolytic bacterium Cellulomonas fimi encodes a protein of 872 amino acids designated cellobiohydrolase A (CbhA). Mature CbhA contains 832 amino acid residues and has a predicted molecular mass of 85,349 Da. It is composed of five domains: an N-terminal catalytic domain, three repeated sequen...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Meinke A,Gilkes NR,Kwan E,Kilburn DG,Warren RA,Miller RC Jr

    更新日期:1994-05-01 00:00:00

  • Autonomous plasmid-like replication of a conjugative transposon.

    abstract::Integrative and conjugative elements (ICEs), a.k.a. conjugative transposons, are mobile genetic elements involved in many biological processes, including pathogenesis, symbiosis and the spread of antibiotic resistance. Unlike conjugative plasmids that are extra-chromosomal and replicate autonomously, ICEs are integrat...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Lee CA,Babic A,Grossman AD

    更新日期:2010-01-01 00:00:00

  • Cytotoxic activity of a recombinant chimaeric protein between Pseudomonas aeruginosa exotoxin A and Corynebacterium diphtheriae diphtheria toxin.

    abstract::A segment of the exotoxin A gene of Pseudomonas aeruginosa, coding for the N-terminal end of domain I and domain II of the toxin (ETA), was genetically fused to the diphtheria toxin gene of Corynebacterium diphtheriae, coding for the N-terminal end of A fragment of diphtheria toxin (DT). The resulting hybrid protein (...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Guidi-Rontani C

    更新日期:1992-05-01 00:00:00

  • Transmembrane signal transduction by the Escherichia coli osmotic sensor, EnvZ: intermolecular complementation of transmembrane signalling.

    abstract::The Escherichia coli regulatory proteins, EnvZ and OmpR, are crucially involved in expression of the outer membrane proteins OmpF/OmpC in response to the medium osmolarity. The EnvZ protein is presumably a membrane-located osmotic sensor (or signal transducer), which exhibits both kinase and phosphatase activities spe...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Tokishita S,Mizuno T

    更新日期:1994-08-01 00:00:00

  • Nucleotide sequence and analysis of the N-terminal coding region of the Spodoptera-active delta-endotoxin gene of Bacillus thuringiensis aizawai 7.29.

    abstract::The nucleotide sequence of a 2711bp DNA segment which contains the N-terminal coding sequence and the 5' flanking region of a crystal protein gene (bta) from Bacillus thuringiensis subsp. aizawai 7.29 has been determined. The coding region encodes an 824 amino-acid polypeptide corresponding to a carboxy-terminally tru...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Sanchis V,Lereclus D,Menou G,Chaufaux J,Guo S,Lecadet MM

    更新日期:1989-02-01 00:00:00

  • Acidianus, Sulfolobus and Metallosphaera surface layers: structure, composition and gene expression.

    abstract::The cell walls of Sulfolobales species consist of proteinaceous S-layers assembled from two polypeptides, SlaA and SlaB. We isolated the large S-layer protein of Acidianus ambivalens and both S-layer subunits of Sulfolobus solfataricus and Metallosphaera sedula, respectively. The slaAB genes, lying adjacently in the c...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Veith A,Klingl A,Zolghadr B,Lauber K,Mentele R,Lottspeich F,Rachel R,Albers SV,Kletzin A

    更新日期:2009-07-01 00:00:00

  • DNA replication-coupled inactivation of DnaA protein in vitro: a role for DnaA arginine-334 of the AAA+ Box VIII motif in ATP hydrolysis.

    abstract::The DnaA protein, which initiates chromosomal replication in Escherichia coli, is negatively regulated by both the sliding clamp of DNA polymerase III holoenzyme and the IdaB protein. We have found that, when the amount of minichromosome is limited in an in vitro replication system, minichromosomal replication-stimula...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Su'etsugu M,Kawakami H,Kurokawa K,Kubota T,Takata M,Katayama T

    更新日期:2001-04-01 00:00:00

  • An E. coli promoter induced by the cessation of growth.

    abstract::The production of the bacterial DNA replication inhibitor Microcin B17 is induced as cultures enter stationary phase. Using S1 nuclease protection assays we have shown that this induction is the result of increased levels of transcription initiation from a promoter located upstream from mcbA, the structural gene for M...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Connell N,Han Z,Moreno F,Kolter R

    更新日期:1987-09-01 00:00:00

  • The role of a stress-response protein in Salmonella typhimurium virulence.

    abstract::We recently described the use of selective transposon mutagenesis to generate a series of avirulent mutants of a pathogenic strain of Salmonella typhimurium. Cloning and sequencing of the insertion sites from two of these mutants reveals that both have identical locations within an open reading frame that is highly ho...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Johnson K,Charles I,Dougan G,Pickard D,O'Gaora P,Costa G,Ali T,Miller I,Hormaeche C

    更新日期:1991-02-01 00:00:00

  • Characterization of a replicon of the moderately promiscuous plasmid, pGSH5000, with features of both the mini-replicon of pCU1 and the ori-2 of F.

    abstract::The dominant, polA1-independent replicon of pGSH500, rep beta (1.8 kb), consists of a cis-acting oriV region of 245 bp; a repB gene that is essential for autonomous replication and 18, 30 to 36 bp iterons which constitute the inc/cop region. The molecular organization of rep beta resembles that of mini-pCU1 (IncN). Fu...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: da Silva-Tatley FM,Steyn LM

    更新日期:1993-03-01 00:00:00

  • Extensive alanine scanning reveals protein-protein and protein-DNA interaction surfaces in the global regulator FlhD from Escherichia coli.

    abstract::FlhD and FlhC are the transcriptional activators of the flagellar regulon. The heterotetrameric complex formed by these two proteins activates the transcription of the class II flagellar genes. The flagellar regulon consists not only of flagellar genes, but also of the chemotactic genes and some receptor proteins. Rec...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Campos A,Matsumura P

    更新日期:2001-02-01 00:00:00

  • The conserved cytoplasmic module of the transmembrane chemoreceptor McpC mediates carbohydrate chemotaxis in Bacillus subtilis.

    abstract::Escherichia coli cells use two distinct sensory circuits during chemotaxis towards carbohydrates. One circuit requires the phosphoenolpyruvate-dependent phosphotransferase system (PTS) and is independent of any specific chemoreceptor, whereas the other uses a chemoreceptor-dependent sensory mechanism analogous to that...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Kristich CJ,Glekas GD,Ordal GW

    更新日期:2003-03-01 00:00:00

  • Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy.

    abstract::Long-term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Low AS,MacKenzie FM,Gould IM,Booth IR

    更新日期:2001-11-01 00:00:00

  • Axiom of determining transcription start points by RNA polymerase in Escherichia coli.

    abstract::To investigate the determining factors in the selection of the transcription start points (tsp) by RNA polymerase of Escherichia coli, we systematically deleted or substituted single base pairs (bps) at 25 putative critical positions in the two extended -10 promoters, P1 and P2, of the gal operon. These changes extend...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Lewis DE,Adhya S

    更新日期:2004-11-01 00:00:00

  • Identification, cloning and sequence analysis of the Bacillus sphaericus 1593 41.9 kD larvicidal toxin gene.

    abstract::A number of strains of the widespread aerobic soil bacterium, Bacillus sphaericus, possess crystalline inclusions of a toxin lethal to a variety of insect (larvae) which are vectors of major tropical diseases. Partial amino acid sequence data from one strain, B. sphaericus 2362 have permitted us to design oligonucleot...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Hindley J,Berry C

    更新日期:1987-09-01 00:00:00

  • Hop-family Helicobacter outer membrane adhesins form a novel class of Type 5-like secretion proteins with an interrupted β-barrel domain.

    abstract::The human stomach pathogen Helicobacter pyloriattaches to healthy and inflamed gastric tissue through members of a paralogous family of 'Helicobacter outer membrane proteins' (Hops), including adhesins BabA, SabA, HopQ, LabA and HopZ. Hops share a conserved 25 kDa C-terminal region that is thought to form an autotrans...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Coppens F,Castaldo G,Debraekeleer A,Subedi S,Moonens K,Lo A,Remaut H

    更新日期:2018-10-01 00:00:00

  • Adaptation of the Brucellae to their intracellular niche.

    abstract::Members of the bacterial genus Brucella are facultative intracellular pathogens that reside predominantly within membrane-bound compartments within two host cell types, macrophages and placental trophoblasts. Within macrophages, the brucellae route themselves to an intracellular compartment that is favourable for surv...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审


    authors: Roop RM 2nd,Bellaire BH,Valderas MW,Cardelli JA

    更新日期:2004-05-01 00:00:00

  • Chromosomal mapping, expression and synthesis of lipopolysaccharide in Pseudomonas aeruginosa: a role for guanosine diphospho (GDP)-D-mannose.

    abstract::Pseudomonas aeruginosa can express two distinct forms of lipopolysaccharide (LPS), called A-band and B-band. As an attempt to understand the molecular biology of the synthesis and regulation of these LPS antigens, a recombinant plasmid, pFV3, containing genes for A-band expression was isolated previously. In the prese...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Lightfoot J,Lam JS

    更新日期:1993-05-01 00:00:00

  • The function of CreA, the carbon catabolite repressor of Aspergillus nidulans, is regulated at the transcriptional and post-transcriptional level.

    abstract::The creA gene of A. nidulans encodes a wide-domain regulatory protein mediating carbon catabolite repression. Northern blot analysis of creA mRNA revealed a complex expression profile: the addition of monosaccharides to a carbon-starved culture of A. nidulans provoked a strong transient stimulation of creA transcript ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Strauss J,Horvath HK,Abdallah BM,Kindermann J,Mach RL,Kubicek CP

    更新日期:1999-04-01 00:00:00

  • An oligopeptide permease responsible for the import of an extracellular signal governing aerial mycelium formation in Streptomyces coelicolor.

    abstract::Morphological differentiation in the filamentous bacterium Streptomyces coelicolor is believed to involve a mechanism of extracellular signalling that culminates with the formation of an aerial mycelium. We have identified a gene cluster designated bldK in which insertional and deletion mutations cause a block in aeri...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Nodwell JR,McGovern K,Losick R

    更新日期:1996-12-01 00:00:00

  • Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans.

    abstract::Candida albicans is the single, most frequently isolated human fungal pathogen. As with most fungal pathogens, the factors which contribute to pathogenesis in C. albicans are not known, despite more than a decade of molecular genetic analysis. Candida albicans was thought to be asexual until the discovery of the MTL l...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Magee BB,Legrand M,Alarco AM,Raymond M,Magee PT

    更新日期:2002-12-01 00:00:00

  • RecA-mediated excision repair: a novel mechanism for repairing DNA lesions at sites of arrested DNA synthesis.

    abstract::In Escherichia coli, bulky DNA lesions are repaired primarily by nucleotide excision repair (NER). Unrepaired lesions encountered by DNA polymerase at the replication fork create a blockage which may be relieved through RecF-dependent recombination. We have designed an assay to monitor the different mechanisms through...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Bichara M,Pinet I,Lambert IB,Fuchs RP

    更新日期:2007-07-01 00:00:00

  • Regulation of quorum sensing in Vibrio harveyi by LuxO and sigma-54.

    abstract::The bioluminescent marine bacterium Vibrio harveyi controls light production (lux) by an elaborate quorum-sensing circuit. V. harveyi produces and responds to two different autoinducer signals (AI-1 and AI-2) to modulate the luciferase structural operon (luxCDABEGH) in response to changes in cell-population density. U...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Lilley BN,Bassler BL

    更新日期:2000-05-01 00:00:00

  • Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus.

    abstract::Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Gora KG,Cantin A,Wohlever M,Joshi KK,Perchuk BS,Chien P,Laub MT

    更新日期:2013-03-01 00:00:00

  • Leishmania mexicana can utilize amino acids as major carbon sources in macrophages but not in animal models.

    abstract::Leishmania parasites target macrophages in their mammalian hosts and proliferate within the mature phagolysosome compartment of these cells. Intracellular amastigote stages are dependent on sugars as a major carbon source in vivo, but retain the capacity to utilize other carbon sources. To investigate whether amastigo...

    journal_title:Molecular microbiology

    pub_type: 杂志文章


    authors: Saunders EC,Naderer T,Chambers J,Landfear SM,McConville MJ

    更新日期:2018-04-01 00:00:00