Abstract:
UNLABELLED:Biofilm formation is responsible for increased antibiotic tolerance in pathogenic bacteria. Cyclic di-GMP (c-di-GMP) is a widely used second-messenger signal that plays a key role in bacterial biofilm formation. c-di-GMP is synthesized by diguanylate cyclases (DGCs), a conserved class of enzymes absent in mammals and hence considered attractive molecular targets for the development of antibiofilm agents. Here, the results of a virtual screening approach aimed at identifying small-molecule inhibitors of the DGC PleD from Caulobacter crescentus are described. A three-dimensional (3D) pharmacophore model, derived from the mode of binding of GTP to the active site of PleD, was exploited to screen the ZINC database of compounds. Seven virtual hits were tested in vitro for their ability to inhibit the activity of purified PleD by using circular dichroism spectroscopy. Two drug-like molecules with a catechol moiety and a sulfonohydrazide scaffold were shown to competitively inhibit PleD at the low-micromolar range (50% inhibitory concentration [IC50] of ∼11 μM). Their predicted binding mode highlighted key structural features presumably responsible for the efficient inhibition of PleD by both hits. These molecules represent the most potent in vitro inhibitors of PleD identified so far and could therefore result in useful leads for the development of novel classes of antimicrobials able to hamper biofilm formation. IMPORTANCE:Biofilm-mediated infections are difficult to eradicate, posing a threatening health issue worldwide. The capability of bacteria to form biofilms is almost universally stimulated by the second messenger c-di-GMP. This evidence has boosted research in the last decade for the development of new antibiofilm strategies interfering with c-di-GMP metabolism. Here, two potent inhibitors of c-di-GMP synthesis have been identified in silico and characterized in vitro by using the well-characterized DGC enzyme PleD from C. crescentus as a structural template and molecular target. Given that the protein residues implied as crucial for enzyme inhibition are found to be highly conserved among DGCs, the outcome of this study could pave the way for the future development of broad-spectrum antibiofilm compounds.
journal_name
J Bacterioljournal_title
Journal of bacteriologyauthors
Fernicola S,Paiardini A,Giardina G,Rampioni G,Leoni L,Cutruzzolà F,Rinaldo Sdoi
10.1128/JB.00742-15subject
Has Abstractpub_date
2015-09-28 00:00:00pages
147-56issue
1eissn
0021-9193issn
1098-5530pii
JB.00742-15journal_volume
198pub_type
杂志文章abstract::Cultural characteristics and serological relationships of pathogenic marine vibrios isolated from fish in the Pacific Northwest were studied. These organisms were compared with cultures of Vibrio anguillarum, a known fish pathogen. On the basis of morphological and cultural characteristics, the Pacific Northwest strai...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.100.3.1242-1247.1969
更新日期:1969-12-01 00:00:00
abstract::Transcription of an aqpZ-lac fusion in a single copy on the Escherichia coli chromosome increased as cells entered the stationary growth phase. This was true in a variety of media, and increased transcription in enriched medium required the RpoS sigma factor. Expression of the aqpZ-lac fusion was not affected by up- o...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.184.15.4304-4307.2002
更新日期:2002-08-01 00:00:00
abstract::Selection for chlorate resistance yields mol (formerly chl) mutants with defects in molybdenum cofactor synthesis. Complementation and genetic mapping analyses indicated that the Klebsiella pneumoniae mol genes are functionally homologous to those of Escherichia coli and occupy analogous genetic map positions. Hypoxan...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.174.19.6298-6302.1992
更新日期:1992-10-01 00:00:00
abstract::Interest in finding small RNAs (sRNAs) in bacteria has significantly increased in recent years due to their regulatory functions. Development of high-throughput methods and more sophisticated computational algorithms has allowed rapid identification of sRNA candidates in different species. However, given their various...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.02359-14
更新日期:2015-01-01 00:00:00
abstract::A mutant of Escherichia coli, previously shown to contain abnormal nucleoside triphosphate pools, was found to be defective in its ability to synthesize thymidine nucleotides. The defect is not in the enzyme thymidylate synthetase but in deoxycytidine triphosphate deaminase, an enzyme that supplies deoxyuridine monoph...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.105.2.666-672.1971
更新日期:1971-02-01 00:00:00
abstract::The SOS response in bacteria includes a global transcriptional response to DNA damage. DNA damage is sensed by the highly conserved recombination protein RecA, which facilitates inactivation of the transcriptional repressor LexA. Inactivation of LexA causes induction (derepression) of genes of the LexA regulon, many o...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.187.22.7655-7666.2005
更新日期:2005-11-01 00:00:00
abstract::Bacillus subtilis undergoes a highly distinctive division during spore formation. It yields two unequal cells, the mother cell and the prespore, and septum formation is completed before the origin-distal 70% of the chromosome has entered the smaller prespore. The mother cell subsequently engulfs the prespore. Two diff...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.01949-06
更新日期:2007-05-01 00:00:00
abstract::Cells of Candida albicans WO-1 switch frequently and reversibly between two colony-forming phenotypes, white and opaque. In the white form, budding cells appear similar to those of most other strains of C. albicans, but in the opaque form, budding cells are larger, are bean shaped, and possess pimples on the wall. The...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.172.1.224-235.1990
更新日期:1990-01-01 00:00:00
abstract::Desulfovibrio vulgaris Hildenborough, a sulfate-reducing bacterium classified as an obligate anaerobe, swam to a preferred oxygen concentration of 0.02 to 0.04% (0.24 to 0.48 microM), a level which also supported growth. Oxygen concentrations of 0.08% and higher arrested growth. We propose that in zones of transition ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.179.17.5598-5601.1997
更新日期:1997-09-01 00:00:00
abstract::Trehalose was found to be utilized more readily than glucose for the growth of Bacillus popilliae NRRL B-2309MC. The pathway of degradation of trehalose was elucidated and found to differ from that reported for other organisms. Trehalase and trehalose phosphorylase activities could not be detected. Rather, trehalose w...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.119.2.484-493.1974
更新日期:1974-08-01 00:00:00
abstract::A comparison of the distribution of CO oxidation activity between soluble and particulate protein fractions obtained after disruption of CO-grown Rhodopseudomonas gelatinosa 1 by French pressure cell breakage and osmotic lysis of spheroplasts suggested that, in situ, the enzyme complex was associated with the cell mem...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.153.1.571-573.1983
更新日期:1983-01-01 00:00:00
abstract::Agrobacterium radiobacter NCIB 11883 was grown in lactose-limited continuous culture at a dilution rate of 0.045/h. Washed cells transported [14C]lactose and [methyl-14C]beta-D-thiogalactoside, a nonmetabolisable analog of lactose, at similar rates and with similar affinities (Km for transport, less than 1 microM). Tr...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.172.4.1703-1710.1990
更新日期:1990-04-01 00:00:00
abstract::Using a system of chromatography through columns of DEAE-Bio-Gel, HTP-Bio-Gel, and CM-Bio-Gel, we isolated and characterized six different (1 leads to 3)-beta-glucanases from cell wall autolysates and cell extracts of Saccharomyces cerevisiae haploid strain 2180B. These enzymes were designated glucanases I, II, IIIA, ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.156.3.1204-1213.1983
更新日期:1983-12-01 00:00:00
abstract::SecA facilitates protein transport across the eubacterial plasma membrane by its association with cargo proteins and the SecYEG translocon, followed by ATP-driven conformational changes that promote protein translocation in a stepwise manner. Whether SecA functions as a monomer or a dimer during this process has been ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.188.1.335-338.2006
更新日期:2006-01-01 00:00:00
abstract::Aerobactin, a dihydroxamate siderophore produced by many strains of enteric bacteria, stimulated the growth of Neisseria gonorrhoeae FA19 and F62 in iron-limiting medium. However, gonococci did not produce detectable amounts of aerobactin in the Escherichia coli LG1522 aerobactin bioassay. We probed gonococcal genomic...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.169.8.3414-3421.1987
更新日期:1987-08-01 00:00:00
abstract::A sulfonic acid found to be a major constituent of spores of Bacillus subtilis was provisionally identified as 3-l-sulfolactic acid. This compound was completely absent from vegetative cells during growth, but large amounts accumulated in sporulating cells just before the development of refractile spores. Essentially ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.98.1.62-68.1969
更新日期:1969-04-01 00:00:00
abstract::XbaI digestion and pulsed-field gel electrophoresis of the genome of Salmonella typhimurium LT2 yields 24 fragments: 23 fragments (total size, 4,807 kb) are from the chromosome, and one fragment (90 kb) is from the virulence plasmid pSLT. Some of the 23 fragments from the chromosome were located on the linkage map by ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.174.5.1662-1672.1992
更新日期:1992-03-01 00:00:00
abstract::Transcription of the dnaA gene of the cyanobacterium Synechocystis sp. strain PCC 6803 is light dependent and yields a monocistronic mRNA, as determined by Northern analysis. Surprisingly, mutants with inactivated dnaA were viable. In batch cultures under standard conditions, the mutants grew like the wild type and di...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.180.18.4946-4949.1998
更新日期:1998-09-01 00:00:00
abstract::A mutant of Escherichia coli resistant to serine hydroxamate which has a large increase in Km for serine of seryl-tRNA synthetase is described. The mutant serS gene was cloned and sequenced and was found to contain a single-base-pair mutation, resulting in the substitution of the residue alanine 262 by valine in motif...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.177.11.3347-3350.1995
更新日期:1995-06-01 00:00:00
abstract:UNLABELLED:Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signal...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.00872-15
更新日期:2016-03-31 00:00:00
abstract::Acid hydrolysates of 140 strains, representing 11 species of the genus Bacteroides, were analyzed by capillary gas-liquid chromatography for total cellular fatty acid. All samples contained components which appeared to be hydroxy fatty acid. The relative amount and chain length distribution of the hydroxy fatty acids,...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.143.2.582-587.1980
更新日期:1980-08-01 00:00:00
abstract::Dehalogenases are key enzymes in the metabolism of halo-organic compounds. This paper describes a systematic approach to the isolation and molecular analysis of two families of bacterial alpha-halocarboxylic acid (alphaHA) dehalogenase genes, called group I and group II deh genes. The two families are evolutionarily u...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.181.8.2535-2547.1999
更新日期:1999-04-01 00:00:00
abstract::The KRE1 gene of Saccharomyces cerevisiae, sacKRE1, appears to be involved in the synthesis of cell wall beta-glucan. S. cerevisiae strains with mutations in the KRE1 gene produce a structurally altered cell wall (1----6)-beta-glucan, which results in resistance to K1 killer toxin. We isolated the canKRE1 gene from Ca...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.173.21.6859-6864.1991
更新日期:1991-11-01 00:00:00
abstract::Lambda transducing phage gamma 16-2 carries the genes envA, ftsZ, ftsA, ddl, and murC and directs the synthesis of six unique proteins in ultraviolet-irradiated cells. Various derivatives of gamma 16-2 carrying smaller segments of the bacterial deoxyribonucleic acid have also been analyzed for their capacity to direct...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.143.3.1281-1288.1980
更新日期:1980-09-01 00:00:00
abstract::A phage-induced cell wall solubilizing enzyme isolated from phage-infected Staphylococcus aureus phage type 80 was purified 588-fold. The pH optimal activity was 6.8 to 7.3, and pH optimal stability, 6.5 to 7.5. It was inhibited by p-hydroxymercuribenzoate, ethylenediaminetetraacetic acid, and specific rabbit antisera...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.93.3.1089-1095.1967
更新日期:1967-03-01 00:00:00
abstract::Expression of the lysine decarboxylase gene (cadA) of Escherichia coli is induced upon external acidification. To dissect the molecular mechanisms responsible for this regulation, we analyzed a 4.2-kbp region upstream from cadA. DNA sequencing revealed two long open reading frames upstream of and on the same strand as...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.174.2.530-540.1992
更新日期:1992-01-01 00:00:00
abstract::When Mucor hiemalis NRRL 3103 was grown in soybean medium, only a small fraction of the proteinase produced by the organism appeared in the culture filtrate, whereas the bulk of the enzyme was bound to the mycelial surface. Optimal pH of the proteinase ranged from 3.0 to 3.5. Inclusion of sodium chloride or other ioni...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.93.6.1794-1799.1967
更新日期:1967-06-01 00:00:00
abstract::Soluble reduced nicotinamide adenine dinucleotide oxidase activity in extracts of Bacillus subtilis spores was stimulated by the addition of not only flavine mononucleotide (FMN) or flavine adenine dinucleotide (FAD) but also alpha-alpha'-dipyridyl or o-phenanthroline. These chelating agents showed stronger effect on ...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.117.3.1017-1022.1974
更新日期:1974-03-01 00:00:00
abstract::IS630 is a 1.15-kilobase sequence in Shigella sonnei that, unlike many mobile elements, seems not to mediate cointegration between different replicons. To assess its transposition, we constructed composite elements containing inverted copies of IS630 flanking a drug resistance gene. We found that these composite eleme...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.172.7.3830-3836.1990
更新日期:1990-07-01 00:00:00
abstract::Southern blot analysis indicated that the gene encoding the constitutive, NADP-linked bile acid 7 alpha-hydroxysteroid dehydrogenase of Eubacterium sp. strain VPI 12708 was located on a 6.5-kb EcoRI fragment of the chromosomal DNA. This fragment was cloned into bacteriophage lambda gt11, and a 2.9-kb piece of this ins...
journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/jb.173.15.4558-4569.1991
更新日期:1991-08-01 00:00:00