CRS-MIS in Candida glabrata: sphingolipids modulate echinocandin-Fks interaction.

Abstract:

:Infections with the azole-refractory yeast Candida glabrata are now commonly treated with the echinocandins caspofungin (CSF) or micafungin (MCF). True resistance (>  32-fold decreased susceptibility) to these lipopeptide inhibitors of cell wall synthesis is rare and strictly associated with mutations in integral membrane proteins Fks1 or Fks2. In contrast, mutants exhibiting 4- to 32-fold CSF reduced susceptibility (CRS) were readily selected in vitro, and surprisingly demonstrated 4- to 32-fold MCF increased susceptibility (MIS). Sequencing and gene deletion demonstrated that CRS-MIS is Fks-independent. To explore alternative mechanisms, we initially employed Saccharomyces cerevisiae, and observed that CRS was conferred by multiple mutations (fen1Δ, sur4Δ, cka2Δ and tsc10-ts) disrupting sphingolipid biosynthesis. Following this lead, C. glabrata fen1Δ and cka2Δ deletants were constructed, and shown to exhibit CRS-MIS. Sphingolipid analysis of CRS-MIS laboratory mutants and clinical isolates demonstrated elevated dihydrosphingosine (DHS) and phytosphingosine (PHS) levels, and consistent with this sequencing revealed fen1, sur4, ifa38 and sur2 mutations. Moreover, exogenous DHS or PHS conferred a CRS-MIS phenotype on wild-type C. glabrata. Exogenous PHS failed, however, to suppress CRS-MIS in a sur2 mutant blocked in conversion of DHS to PHS, implying that accumulation of these intermediates confers CRS-MIS. We conclude that membrane sphingolipids modulate echinocandin-Fks interaction.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Healey KR,Katiyar SK,Raj S,Edlind TD

doi

10.1111/j.1365-2958.2012.08194.x

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

303-13

issue

2

eissn

0950-382X

issn

1365-2958

journal_volume

86

pub_type

杂志文章
  • The stable BRP signal peptide causes lethality but is unable to provoke the translocation of cloacin DF13 across the cytoplasmic membrane of Escherichia coli.

    abstract::The bacteriocin release protein (BRP) mediates the secretion of cloacin DF13. The BRP precursor is slowly processed to yield the mature BRP and its stable signal peptide which is also involved in cloacin DF13 secretion. The function of the stable BRP signal peptide was analysed by constructing two plasmids. First, the...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01406.x

    authors: van der Wal FJ,Oudega B,Kater MM,ten Hagen-Jongman CM,de Graaf FK,Luirink J

    更新日期:1992-08-01 00:00:00

  • Bacillus subtilis GlnR contains an autoinhibitory C-terminal domain required for the interaction with glutamine synthetase.

    abstract::The Bacillus subtilis GlnR transcription factor regulates gene expression in response to changes in nitrogen availability. Glutamine synthetase transmits the nitrogen regulatory signal to GlnR. The DNA-binding activity of GlnR is activated by a transient protein-protein interaction with feedback-inhibited glutamine sy...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06162.x

    authors: Wray LV Jr,Fisher SH

    更新日期:2008-04-01 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

    doi:10.1111/j.1365-2958.1991.tb02122.x

    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

  • Phenotypic repertoire of the FNR regulatory network in Escherichia coli.

    abstract::The FNR protein in Escherichia coli is an O(2) sensor that modifies global gene expression to adapt the cell to anaerobic growth. Regulation of FNR involves continuous cycling of the protein between its active and inactive states under aerobic conditions without apparent function. This raises the question of what bene...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07437.x

    authors: Tolla DA,Savageau MA

    更新日期:2011-01-01 00:00:00

  • Testing the '+2 rule' for lipoprotein sorting in the Escherichia coli cell envelope with a new genetic selection.

    abstract::We report a novel strategy for selecting mutations that mislocalize lipoproteins within the Escherichia coli cell envelope and describe the mutants obtained. A strain carrying a deletion of the chromosomal malE gene, coding for the periplasmic maltose-binding protein (MalE), cannot use maltose unless a wild-type copy ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01647.x

    authors: Seydel A,Gounon P,Pugsley AP

    更新日期:1999-11-01 00:00:00

  • SeqA-mediated stimulation of a promoter activity by facilitating functions of a transcription activator.

    abstract::It was demonstrated recently that the SeqA protein, a main negative regulator of Escherichia coli chromosome replication initiation, is also a specific transcription factor. SeqA specifically activates the bacteriophage lambda pR promoter while revealing no significant effect on the activity of another lambda promoter...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03392.x

    authors: Słomińska M,Konopa G,Ostrowska J,Kedzierska B,Wegrzyn G,Wegrzyn A

    更新日期:2003-03-01 00:00:00

  • Expanded linkage map of Erwinia chrysanthemi strain 3937.

    abstract::In this paper we describe the chromosomal location of various loci in Erwinia chrysanthemi strain 3937. Auxotrophic markers were obtained by chemical mutagenesis, antibiotic resistances were isolated spontaneously and mutations in sugar utilization were obtained by means of Mu insertions. These markers were located on...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1989.tb00204.x

    authors: Hugouvieux-Cotte-Pattat N,Reverchon S,Robert-Baudouy J

    更新日期:1989-05-01 00:00:00

  • Overexpression, solubilization and refolding of a genetically engineered derivative of the penicillin-binding protein 3 of Escherichia coli K12.

    abstract::Replacement of the amino-terminal 40-amino-acid region of the 588-amino-acid precursor of the membrane-bound penicillin-binding protein 3 (PBP3) by the decapeptide MKGKEFQAWI was carried out by altering the amino-coding end of the ftsI gene. Insertion of the modified gene into a runaway-replication plasmid under the c...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1988.tb00058.x

    authors: Belder JB,Nguyen-Distèche M,Houba-Herin N,Ghuysen JM,Maruyama IN,Hara H,Hirota Y,Inouye M

    更新日期:1988-07-01 00:00:00

  • The DivJ, CbrA and PleC system controls DivK phosphorylation and symbiosis in Sinorhizobium meliloti.

    abstract::Sinorhizobium meliloti is a soil bacterium that invades the root nodules it induces on Medicago sativa, whereupon it undergoes an alteration of its cell cycle and differentiates into nitrogen-fixing, elongated and polyploid bacteroid with higher membrane permeability. In Caulobacter crescentus, a related alphaproteoba...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12347

    authors: Pini F,Frage B,Ferri L,De Nisco NJ,Mohapatra SS,Taddei L,Fioravanti A,Dewitte F,Galardini M,Brilli M,Villeret V,Bazzicalupo M,Mengoni A,Walker GC,Becker A,Biondi EG

    更新日期:2013-10-01 00:00:00

  • The Escherichia coli unc transcription terminator enhances expression of uncC, encoding the epsilon subunit of F1-ATPase, from plasmids by stabilizing the transcript.

    abstract::The effect of the unc transcription terminator on expression of uncC, encoding the epsilon subunit of Escherichia coli F1-ATPase, from plasmids was studied. The cloned sequence in pTK1 included the uncC ribosome binding site, the uncC structural gene, and the unc transcription terminator. The cloned region in pSD37 wa...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1990.tb02043.x

    authors: Patel AM,Dallmann HG,Skakoon EN,Kapala TD,Dunn SD

    更新日期:1990-11-01 00:00:00

  • Selective inactivation of SIDER2 retroposon-mediated mRNA decay contributes to stage- and species-specific gene expression in Leishmania.

    abstract::Despite their high genomic synteny, the Leishmania major and Leishmania infantum species exhibit extensive differences in mRNA expression patterns throughout the parasite's development. Yet, the underlying mechanisms for this species-specific differential gene expression are largely unknown. Here we report that Short ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07226.x

    authors: Müller M,Padmanabhan PK,Papadopoulou B

    更新日期:2010-07-01 00:00:00

  • A Francisella virulence factor catalyses an essential reaction of biotin synthesis.

    abstract::We recently identified a gene (FTN_0818) required for Francisella virulence that seemed likely involved in biotin metabolism. However, the molecular function of this virulence determinant was unclear. Here we show that this protein named BioJ is the enzyme of the biotin biosynthesis pathway that determines the chain l...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12460

    authors: Feng Y,Napier BA,Manandhar M,Henke SK,Weiss DS,Cronan JE

    更新日期:2014-01-01 00:00:00

  • pH-regulated activation and release of a bacteria-associated phospholipase C during intracellular infection by Listeria monocytogenes.

    abstract::Listeria monocytogenes grows in the cytosol of mammalian cells and spreads from cell to cell without exiting the intracellular milieu. During cell-cell spread, bacteria become transiently entrapped in double-membrane vacuoles. Escape from these vacuoles is mediated in part by a bacterial phospholipase C (PC-PLC), whos...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2000.01708.x

    authors: Marquis H,Hager EJ

    更新日期:2000-01-01 00:00:00

  • Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase.

    abstract::Toxin-antitoxin loci have been identified in almost all free-living prokaryotes, often in high copy numbers. The biological function and molecular targets of the abundant vapBC loci are not yet known. Here we analyse the vapBC loci of Salmonella LT2 and Shigella plasmid pMYSH6000. Both loci encode putative PIN (PilT N...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06694.x

    authors: Winther KS,Gerdes K

    更新日期:2009-05-01 00:00:00

  • What are archaebacteria: life's third domain or monoderm prokaryotes related to gram-positive bacteria? A new proposal for the classification of prokaryotic organisms.

    abstract::The evolutionary relationship within prokaryotes is examined based on signature sequences (defined as conserved inserts or deletions shared by specific taxa) and phylogenies derived from different proteins. Archaebacteria are indicated as being monophyletic by a number of proteins related to the information transfer p...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2958.1998.00978.x

    authors: Gupta RS

    更新日期:1998-08-01 00:00:00

  • Clonally variant gene families in Plasmodium falciparum share a common activation factor.

    abstract::The genome of the malaria parasite Plasmodium falciparum contains several multicopy gene families, including var, rifin, stevor and Pfmc-2TM. These gene families undergo expression switching and appear to play a role in antigenic variation. It has recently been shown that forcing parasites to express high copy numbers...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06846.x

    authors: Howitt CA,Wilinski D,Llinás M,Templeton TJ,Dzikowski R,Deitsch KW

    更新日期:2009-09-01 00:00:00

  • Cloning and characterization of fxp, the flexible pilin gene of Aeromonas hydrophila.

    abstract::The flexible pilus of Aeromonas hydrophila is a morphologically and biochemically unique organelle which binds eukaryotic cell surfaces and whose expression is induced by specific physiochemical conditions. fxp, the structural gene coding for the flexible pilus subunit, was localized on a 7.6kb plasmid of A. hydrophil...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01449.x

    authors: Ho AS,Sohel I,Schoolnik GK

    更新日期:1992-09-01 00:00:00

  • The endosomal sorting complex required for transport machinery influences haem uptake and capsule elaboration in Cryptococcus neoformans.

    abstract::Iron availability is a key determinant of virulence in the pathogenic fungus Cryptococcus neoformans. Previous work revealed that the ESCRT (endosomal sorting complex required for transport) protein Vps23 functions in iron acquisition, capsule formation and virulence. Here, we further characterized the ESCRT machinery...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12985

    authors: Hu G,Caza M,Cadieux B,Bakkeren E,Do E,Jung WH,Kronstad JW

    更新日期:2015-06-01 00:00:00

  • A haem cofactor is required for redox and light signalling by the AppA protein of Rhodobacter sphaeroides.

    abstract::The AppA protein of Rhodobacter sphaeroides is unique in its ability to sense and transmit redox signals as well as light signals. By functioning as antagonist to the PpsR transcriptional repressor, it regulates the expression of photosynthesis genes in response to these environmental stimuli. Here we show binding of ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.05724.x

    authors: Han Y,Meyer MH,Keusgen M,Klug G

    更新日期:2007-05-01 00:00:00

  • Transcriptional coupling of DNA repair in sporulating Bacillus subtilis cells.

    abstract::In conditions of halted or limited genome replication, like those experienced in sporulating cells of Bacillus subtilis, a more immediate detriment caused by DNA damage is altering the transcriptional programme that drives this developmental process. Here, we report that mfd, which encodes a conserved bacterial protei...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12417

    authors: Ramírez-Guadiana FH,Del Carmen Barajas-Ornelas R,Ayala-García VM,Yasbin RE,Robleto E,Pedraza-Reyes M

    更新日期:2013-12-01 00:00:00

  • Role of Escherichia coli DNA polymerase I in chromosomal DNA replication fidelity.

    abstract::We have investigated the possible role of Escherichia coli DNA polymerase (Pol) I in chromosomal replication fidelity. This was done by substituting the chromosomal polA gene by the polAexo variant containing an inactivated 3'-->5' exonuclease, which serves as a proofreader for this enzyme's misinsertion errors. Using...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06921.x

    authors: Makiela-Dzbenska K,Jaszczur M,Banach-Orlowska M,Jonczyk P,Schaaper RM,Fijalkowska IJ

    更新日期:2009-12-01 00:00:00

  • Vital role for the Plasmodium actin capping protein (CP) beta-subunit in motility of malaria sporozoites.

    abstract::Summary Successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. Sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. A unique feature of this motor machinery is the presence of very short subpellicular ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06828.x

    authors: Ganter M,Schüler H,Matuschewski K

    更新日期:2009-12-01 00:00:00

  • Local silencing controls the oxidative stress response and the multidrug resistance in Candida glabrata.

    abstract::In Candida glabrata, the sirtuins Sir2 and Hst1 control the expression of a wide number of genes including adhesins required for host colonization and niacin transporters needed for growth. Given that these sirtuins can be inactivated during infection, we asked if their inhibition could modify the response of C. glabr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12247

    authors: Orta-Zavalza E,Guerrero-Serrano G,Gutiérrez-Escobedo G,Cañas-Villamar I,Juárez-Cepeda J,Castaño I,De Las Peñas A

    更新日期:2013-06-01 00:00:00

  • Structural and genetic analysis of the bvg locus in Bordetella species.

    abstract::The bvg locus contains two genes, bvgA and bvgS, which control the expression of the virulence-associated genes in Bordetella species by a system similar to the two-component systems used by a variety of bacterial species to respond to environmental stimuli. We determined the nucleotide sequence of the bvg loci of Bor...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1991.tb02093.x

    authors: Aricò B,Scarlato V,Monack DM,Falkow S,Rappuoli R

    更新日期:1991-10-01 00:00:00

  • Clostridium difficile toxin expression is inhibited by the novel regulator TcdC.

    abstract::Clostridium difficile, an emerging nosocomial pathogen of increasing clinical significance, produces two large protein toxins that are responsible for the cellular damage associated with the disease. The precise mechanisms by which toxin synthesis is regulated in response to environmental change have yet to be discove...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.05739.x

    authors: Matamouros S,England P,Dupuy B

    更新日期:2007-06-01 00:00:00

  • CPMK2, an SLT2-homologous mitogen-activated protein (MAP) kinase, is essential for pathogenesis of Claviceps purpurea on rye: evidence for a second conserved pathogenesis-related MAP kinase cascade in phytopathogenic fungi.

    abstract::Cpmk2, encoding a mitogen-activated protein (MAP) kinase from the ascomycete Claviceps purpurea, is an orthologue of SLT2 from Saccharomyces cerevisiae, the first isolated from a biotrophic, non-appressorium-forming pathogen. Deletion mutants obtained by a gene replacement approach show impaired vegetative properties ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.03133.x

    authors: Mey G,Held K,Scheffer J,Tenberge KB,Tudzynski P

    更新日期:2002-10-01 00:00:00

  • Switching aconitase B between catalytic and regulatory modes involves iron-dependent dimer formation.

    abstract::In addition to being the major citric acid cycle aconitase in Escherichia coli the aconitase B protein (AcnB) is also a post-transcriptional regulator of gene expression. The AcnB proteins represent a distinct branch of the aconitase superfamily that possess a HEAT-like domain (domain 5). The HEAT domains of other pro...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04610.x

    authors: Tang Y,Guest JR,Artymiuk PJ,Green J

    更新日期:2005-06-01 00:00:00

  • Structural dynamics of translating ribosomes: 16S ribosomal RNA bases that may move twice during translocation.

    abstract::Recent footprinting, sedimentation and neutron-scattering results obtained in vivo or on pre-translocation and post-translocation ribosomal complexes are integrated with cross-linking and immunoelectron microscopy information. It is proposed that the 30S subunit pulses during translocation and that its pre- and post-t...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2958.1994.tb00378.x

    authors: Laughrea M

    更新日期:1994-03-01 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

    doi:10.1111/j.1365-2958.1987.tb00512.x

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

    更新日期:1987-09-01 00:00:00

  • Disulphide bridge formation in the periplasm of Escherichia coli: beta-lactamase:: human IgG3 hinge fusions as a model system.

    abstract::We report the construction and the expression in Escherichia coli of three different fusion genes encoding the extended human IgG3 hinge region (Hi) fused in-phase to the C-terminal end of bacterial TEM1 beta-lactamase (Bla). In the first fusion gene blahi, TEM1 beta-lactamase (Bla). In the first fusion gene blahi, th...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01394.x

    authors: De Sutter K,Remaut E,Fiers W

    更新日期:1992-08-01 00:00:00