bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of the Antiadhesin Octyl
O
-(2-Acetamido-2-Deoxy-β-
d
- Galactopyranosyl)-(1-4)-2-
O
-Propyl-β-
d
-Galactopyranoside (Fimbrigal-P) in a Rat Oral Candidiasis Model
Authors: Foldvari M. , Jaafari M. R. , Radhi J. , Segal D. 
Published: June 2005

ABSTRACT

Adherence of
Candida albicans
to buccal epithelial cells via its fimbrial subunit requires the minimal disaccharide sequence β-GalNAc(1-4)-β-galactosidase in host cell receptors asialo-GM1 or asialo-GM2. This and other disaccharides and some of its synthetic derivatives have been shown to inhibit purified fimbrial or pathogen binding in vitro. This study evaluates the in vivo efficacy of the propyl derivative of this disaccharide, octyl
O
-(2-acetamido-2-deoxy-β-
d
-galactopyranosyl)-(1-4)-2-
O
-propyl-β-
d
-galactopyranoside, or Fimbrigal-P, incorporated into a mucoadhesive polymer formulation in a rat oral candidiasis model. Colony counts of microcurette samples from the oral cavity and tongue homogenates were used to estimate the effectiveness of four treatment modalities to reduce oral fungal burden. All treatment modalities (preventative, premixing with the
Candida
inoculant, drinking water, and treatment) significantly reduced fungal burden compared to untreated control animals by day 9; however, the preventative and premixing approaches provided a faster rate of fungal clearance. The low toxicity and immunogenicity of this synthetic carbohydrate and its stability in saliva, as demonstrated by high-performance liquid chromatography, make it a promising candidate for the prevention and treatment of microbial infections in which the pathogen relies on the β-GalNAc(1-4)-β-galactosidase disaccharide to establish adherence.
Identical Penicillin-Binding Domains in Penicillin-Binding Proteins of
Streptococcus pneumoniae
Clinical Isolates with Different Levels of β-Lactam Resistance
Authors: Chesnel Laurent , Carapito Raphaël , Croizé Jacques , Dideberg Otto , Vernet Thierry , Zapun André 
Published: June 2005

ABSTRACT

We have sequenced the penicillin-binding domains of the complete repertoire of penicillin-binding proteins and MurM from 22 clinical isolates of
Streptococcus pneumoniae
that span a wide range of β-lactam resistance levels. Evidence of mosaicism was found in the genes encoding PBP 1a, PBP 2b, PBP 2x, MurM, and, possibly, PBP 2a. Five isolates were found to have identical PBP and MurM sequences, even though the MICs for penicillin G ranged from 0.25 to 2.0 mg/liter. When the sequences encoding PBP 1a, PBP 2b, and PBP 2x from one of these isolates were used to transform laboratory strain R6, the resulting strain had a resistance level higher than that of the less resistant isolates carrying that PBP set but lower than that of the most resistant isolates carrying that PBP set. This result demonstrates that if the R6 strain is arbitrarily defined as the standard genotype, some wild genetic backgrounds can either increase or decrease the PBP-based resistance phenotype.
Antimicrobial Susceptibility of
Streptococcus pneumoniae
in Eight European Countries from 2001 to 2003
Authors: Reinert Ralf René , Reinert Susanne , van der Linden Mark , Cil Murat Y. , Al-Lahham Adnan , Appelbaum Peter 
Published: June 2005

ABSTRACT

Susceptibility testing results for
Streptococcus pneumoniae
isolates (
n
= 2,279) from eight European countries, examined in the PneumoWorld Study from 2001 to 2003, are presented. Overall, 24.6% of
S. pneumoniae
isolates were nonsusceptible to penicillin G and 28.0% were resistant to macrolides. The prevalence of resistance varied widely between European countries, with the highest rates of penicillin G and macrolide resistance reported from Spain and France. Serotype 14 was the leading serotype among penicillin G- and macrolide-resistant
S. pneumoniae
isolates. One strain (PW 158) showed a combination of an efflux type of resistance with a 23S rRNA mutation (A2061G, pneumococcal numbering; A2059G,
Escherichia coli
numbering). Six strains which showed negative results for
mef
(A) and
erm
(B) in repeated PCR assays had mutations in 23S rRNA or alterations in the L4 ribosomal protein (two strains). Fluoroquinolone resistance rates (levofloxacin MIC ≥ 4 μg/ml) were low (Austria, 0%; Belgium, 0.7%; France, 0.9%; Germany, 0.4%; Italy, 1.3%; Portugal, 1.2%; Spain, 1.0%; and Switzerland, 0%). Analysis of quinolone resistance-determining regions showed eight strains with a Ser81 alteration in
gyrA
; 13 of 18 strains showed a Ser79 alteration in
parC
. The clonal profile, as analyzed by multilocus sequence typing (MLST), showed that the 18 fluoroquinolone-resistant strains were genetically heterogeneous. Seven of the 18 strains belonged to new sequence types not hitherto described in the MLST database. Europe-wide surveillance for monitoring of the further spread of these antibiotic-resistant
S. pneumoniae
clones is warranted.
Antifolate Activity of Epigallocatechin Gallate against
Stenotrophomonas maltophilia
Authors: Navarro-Martínez María Dolores , Navarro-Perán Enma , Cabezas-Herrera Juan , Ruiz-Gómez Joaquín , García-Cánovas Francisco , Rodríguez-López José Neptuno 
Published: June 2005

ABSTRACT

The catechin epigallocatechin gallate, one of the main constituents of green tea, showed strong antibiotic activity against 18 isolates of
Stenotrophomonas maltophilia
(MIC range, 4 to 256 μg/ml). In elucidating its mechanism of action, we have shown that epigallocatechin gallate is an efficient inhibitor of
S. maltophilia
dihydrofolate reductase, a strategic enzyme that is considered an attractive target for the development of antibacterial agents. The inhibition of
S. maltophilia
dihydrofolate reductase by this tea compound was studied and compared with the mechanism of a nonclassical antifolate compound, trimethoprim. Investigation of dihydrofolate reductase was undertaken with both a trimethoprim-susceptible
S. maltophilia
isolate and an isolate with a high level of resistance. The enzymes were purified using ammonium sulfate precipitation, gel filtration, and methotrexate affinity chromatography. The two isolates showed similar levels of dihydrofolate reductase expression and similar substrate kinetics. However, the dihydrofolate reductase from the trimethoprim-resistant isolate demonstrated decreased susceptibility to inhibition by trimethoprim and epigallocatechin gallate. As with other antifolates, the action of epigallocatechin gallate was synergistic with that of sulfamethoxazole, a drug that blocks folic acid metabolism in bacteria, and the inhibition of bacterial growth was attenuated by including leucovorin in the growth medium. We conclude that the mechanism of action of epigallocatechin gallate on
S. maltophilia
is related to its antifolate activity.
Antimicrobial Peptide Therapeutics for Cystic Fibrosis
Authors: Zhang Lijuan , Parente Jody , Harris Scott M. , Woods Donald E. , Hancock Robert E. W. , Falla Timothy J. 
Published: June 2005

ABSTRACT

Greater than 90% of lung infections in cystic fibrosis (CF) patients are caused by
Pseudomonas aeruginosa
, and the majority of these patients subsequently die from lung damage. Current therapies are either targeted at reducing obstruction, reducing inflammation, or reducing infection. To identify potential therapeutic agents for the CF lung, 150 antimicrobial peptides consisting of three distinct structural classes were screened against mucoid and multidrug-resistant clinical isolates of
P. aeruginosa
,
Stenotrophomonas maltophilia
,
Achromobacter xylosoxidans
, and
Staphylococcus aureus
. Five peptides that retained potent antimicrobial activities in physiological salt and divalent cation environment were further characterized in vivo using a rat chronic lung infection model. All animals were inoculated intratracheally with 10
4
P. aeruginosa
mucoid PAO1 cells in agar beads. Three days following inoculation treatment was initiated. Animals were treated daily for 3 days with 100 μl of peptide solution (1 mg/ml) in 10 mM sodium citrate, which was deposited via either intratracheal instillation or aerosolization. Control animals received daily exposure to vehicle alone. At the end of the treatment the lungs of the animals were removed for quantitative culture. Four peptides, HBCM2, HBCM3, HBCPα-2, and HB71, demonstrated significant reduction in
Pseudomonas
bioburden in the lung of rats. Further in vivo studies provided direct evidence that anti-inflammatory activity was associated with three of these peptides. Therefore, small bioactive peptides have the potential to attack two of the components responsible for the progression of lung damage in the CF disease: infection and inflammation.
Evaluation of a New Line Probe Assay for Rapid Identification of
gyrA
Mutations in
Mycobacterium tuberculosis
Authors: Giannoni Federico , Iona Elisabetta , Sementilli Federica , Brunori Lara , Pardini Manuela , Migliori Giovanni Battista , Orefici Graziella , Fattorini Lanfranco 
Published: June 2005

ABSTRACT

Resistance of
Mycobacterium tuberculosis
to fluoroquinolones (FQ) results mostly from mutations in the
gyrA
gene. We developed a reverse hybridization-based line probe assay in which oligonucleotide probes carrying the wild-type
gyrA
sequence, a serine-to-threonine (S95T) polymorphism, and
gyrA
mutations (A90V, A90V-S95T, S91P, S91P-S95T, D94A, D94N, D94G-S95T, D94H-S95T) were immobilized on nitrocellulose strips and hybridized with digoxigenin-labeled PCR products obtained from
M. tuberculosis
strains. When a mutated PCR product was used, hybridization occurred to the corresponding mutated probe but not to the wild-type probe. A panel of
M. tuberculosis
complex strains including 19 ofloxacin-resistant (OFL-R) and 9 ofloxacin-susceptible (OFL-S)
M. tuberculosis
strains was studied for detection and identification of
gyrA
mutations by the line probe assay and nucleotide sequencing, in comparison with testing of in vitro susceptibility to FQ. Results were 100% concordant with those of nucleotide sequencing. The S95T polymorphism, which is not related to FQ resistance, was found in 5 OFL-S and 2 OFL-R strains; the other 17 OFL-R strains harbored single mutations associated with serine or threonine at codon 95. No mutations were found in the other OFL-S strains. Overall, on the basis of the MICs on solid medium, the new line probe assay correctly identified all OFL-S and 17 out of 19 (89.5%) OFL-R strains. A nested-PCR protocol was also evaluated for the assay to amplify PCR products from
M. tuberculosis
-spiked sputa, with a good specificity and a sensitivity of 2 × 10
3
M. tuberculosis
CFU per ml of sputum.
Phage P68 Virion-Associated Protein 17 Displays Activity against Clinical Isolates of
Staphylococcus aureus
Authors: Takáč Marian , Bläsi Udo 
Published: June 2005

ABSTRACT

Phage-encoded murein hydrolases are either part of the lysis cassette or found as structural components of the phage virion. Here, we show that
Staphylococcus aureus
bacteriophage P68 contains a virion-associated muralytic enzyme. Protein 17 has a composite structure. The N-terminal part comprises the muralytic activity, whereas the C-terminal part is required for binding to the cell surface. A high multiplicity of infection with phage P68 caused rapid lysis, and purified protein 17 triggered premature lysis when added to
S. aureus
cells prior to infection with P68, suggesting that it functions to weaken the murein at the site of phage DNA entry. Protein 17 displayed activity against clinical
S. aureus
isolates, which are resistant to infection by phage P68, demonstrating that the protein targets surface structures distinct from the phage receptor. This broad activity spectrum of protein 17 could qualify virion-associated muralytic enzymes as attractive antimicrobials.
Identification of a New Allelic Variant of theAcinetobacter baumanniiCephalosporinase, ADC-7 β-Lactamase: Defining a Unique Family of Class C Enzymes
Authors: Hujer Kristine M. , Hamza Nashaat S. , Hujer Andrea M. , Perez Federico , Helfand Marion S. , Bethel Christopher R. , Thomson Jodi M. , Anderson Vernon E. , Barlow Miriam , Rice Louis B. , Tenover Fred C. , Bonomo Robert A. 
Published: June 2005

ABSTRACTAcinetobacterspp. are emerging as opportunistic hospital pathogens that demonstrate resistance to many classes of antibiotics. In a metropolitan hospital in Cleveland, a clinical isolate ofAcinetobacter baumanniithat tested resistant to cefepime and ceftazidime (MIC = 32 μg/ml) was identified. Herein, we sought to determine the molecular basis for the extended-spectrum-cephalosporin resistance. Using analytical isoelectric focusing, a β-lactamase with a pI of ≥9.2 was detected. PCR amplification with specificA. baumanniicephalosporinase primers yielded a 1,152-bp product which, when sequenced, identified a novel 383-amino-acid class C enzyme. Expressed inEscherichia coliDH10B, this β-lactamase demonstrated greater resistance against ceftazidime and cefotaxime than cefepime (4.0 μg/ml versus 0.06 μg/ml). The kinetic characteristics of this β-lactamase were similar to other cephalosporinases found inAcinetobacterspp. In addition, this cephalosporinase was inhibited by meropenem, imipenem, ertapenem, and sulopenem (Ki< 40 μM). The amino acid compositions of this novel enzyme and other class C β-lactamases thus far described forA. baumannii,Acinetobactergenomic species 3, andOligella urethralisin Europe and South Africa suggest that this cephalosporinase defines a unique family of class C enzymes. We propose a uniform designation for this family of cephalosporinases (Acinetobacter-derivedcephalosporinases [ADC]) found inAcinetobacterspp. and identify this enzyme as ADC-7 β-lactamase. The coalescence ofAcinetobacter ampCβ-lactamases into a single common ancestor and the substantial phylogenetic distance separating them from otherampCgenes support the logical value of developing a system of nomenclature for theseAcinetobactercephalosporinase genes.
Worldwide Disseminated
armA
Aminoglycoside Resistance Methylase Gene Is Borne by Composite Transposon Tn
1548
Authors: Galimand M. , Sabtcheva S. , Courvalin P. , Lambert T. 
Published: June 2005

ABSTRACT

The
armA
(
a
minoglycoside
r
esistance
m
ethylase) gene, which confers resistance to 4,6-disubstituted deoxystreptamines and fortimicin, was initially found in
Klebsiella pneumoniae
BM4536 on IncL/M plasmid pIP1204 of ca. 90 kb which also encodes the extended-spectrum β-lactamase CTX-M-3. Thirty-four enterobacteria from various countries that were likely to produce a CTX-M enzyme since they were more resistant to cefotaxime than to ceftazidime were studied. The
armA
gene was detected in 12 clinical isolates of
Citrobacter freundii
,
Enterobacter cloacae
,
Escherichia coli
,
K. pneumoniae
,
Salmonella enterica
, and
Shigella flexneri
, in which it was always associated with
bla
CTX-M-3
on an IncL/M plasmid. Conjugation, analysis of DNA sequences, PCR mapping, and plasmid conduction experiments indicated that the
armA
gene was part of composite transposon Tn
1548
together with genes
ant3"9
,
sul1
, and
dfrXII
, which are responsible for resistance to streptomycin-spectinomycin, sulfonamides, and trimethoprim, respectively. The 16.6-kb genetic element was flanked by two copies of IS
6
and migrated by replicative transposition. This observation accounts for the presence of
armA
on self-transferable plasmids of various incompatibility groups and its worldwide dissemination. It thus appears that posttranscriptional modification of 16S rRNA confers high-level resistance to all the clinically available aminoglycosides except streptomycin in gram-negative human and animal pathogens.
Mechanisms of Resistance to Imipenem and Ampicillin in
Enterococcus faecalis
Authors: Ono Seiji , Muratani Tetsuro , Matsumoto Tetsuro 
Published: June 2005

ABSTRACT

We found ampicillin- and imipenem-resistant isolates of
vanA
-possessing
Enterococcus faecalis
with MICs of 8 to 16 μg/ml and 4 to 32 μg/ml, respectively. There have been few reports about penicillin- and imipenem-resistant
E. faecalis
. Two mechanisms of beta-lactam resistance in
E. faecalis
, the production of beta-lactamase and the overproduction of penicillin-binding proteins (PBPs), have been reported. The resistant isolates in the current study did not produce any beta-lactamases and analysis of the PBPs showed no overproduction. However, the affinities of PBP4 for beta-lactams in the resistant strains were lower than those of susceptible strains but the affinities of other PBPs for beta-lactams did not change. Accordingly, whole
pbp4
fragments from these resistant isolates were sequenced. Two amino acid substitutions at positions 520 and 605 were observed in the highly resistant strains compared to the susceptible ones, Pro520Ser and Tyr605His, and a single Tyr605His amino acid substitution was found in the low-resistance strains. These two point mutations exist in the region between the active-site-defining motifs SDN and KTG of the penicillin-binding domain, the main target of beta-lactams. A strong correlation was seen between these substitutions and decreasing affinities of PBP4 to beta-lactams. In
E. faecalis
, resistance due to mutations in PBPs has not been reported, though it has in
Enterococcus faecium
. Our results suggest that development of high-level resistance to penicillins and imipenem depends on point mutations of PBP4 at positions 520 and 605.
In Vitro Synergy of Ciprofloxacin and Gatifloxacin against Ciprofloxacin-Resistant
Pseudomonas aeruginosa
Authors: Pankey George A. , Ashcraft Deborah S. 
Published: June 2005

ABSTRACT

Multidrug-resistant
Pseudomonas aeruginosa
with combined decreased susceptibility to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being found as a cause of nosocomial infections. It is important to look for combinations of drugs that might be synergistic. Ciprofloxacin resistance by
P. aeruginosa
is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8-methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in vitro study using an Etest synergy method and time-kill assay suggested synergy of ciprofloxacin and gatifloxacin against
P. aeruginosa
. Synergy testing was performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA distinct, U.S.
P. aeruginosa
isolates. Etest MICs for ciprofloxacin were 4 to >32 μg/ml, and for gatifloxacin they were >32 μg/ml. Ciprofloxacin plus gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31
P. aeruginosa
isolates using a summation fractional inhibitory concentration of ≤0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time-kill assay. No antagonism was detected. The remaining isolates were indifferent to the combination. The Etest method and time-kill assay were 65% (20/31) concordant. The mechanism of the in vitro synergy may include
P. aeruginosa
ciprofloxacin efflux pump inhibition by gatifloxacin.
Structural and Functional Study of the Phenicol-Specific Efflux Pump FloR Belonging to the Major Facilitator Superfamily
Authors: Braibant Martine , Chevalier Jacqueline , Chaslus-Dancla Elisabeth , Pagès Jean-Marie , Cloeckaert Axel 
Published: June 2005

ABSTRACT

The florfenicol-chloramphenicol resistance gene
floR
from
Salmonella enterica
was previously identified and postulated to belong to the major facilitator (MF) superfamily of drug exporters. Here, we confirmed a computer-predicted transmembrane topological model of FloR, using the
phoA
gene fusion method, and classified this protein in the DHA12 family (containing 12 transmembrane domains) of MF efflux transporters. We also showed that FloR is a transporter specific for structurally associated phenicol drugs (chloramphenicol, florfenicol, thiamphenicol) which utilizes the proton motive force to energize an active efflux mechanism. By site-directed mutagenesis of specific charged residues belonging to putative transmembrane segments (TMS), two residues essential for active efflux function, D23 in TMS1 and R109 in TMS4, were identified. Of these, the acidic residue D23 seems to participate directly in the affinity pocket involved in phenicol derivative recognition. A third residue, E283 in TMS9, seems to be necessary for correct membrane folding of the transporter.
Peptides Selected for Binding to a Virulent Strain of
Haemophilus influenzae
by Phage Display Are Bactericidal
Authors: Bishop-Hurley Sharon L. , Schmidt Francis J. , Erwin Alice L. , Smith Arnold L. 
Published: June 2005

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHi) is an obligate parasite of the oropharynx of humans, in whom it commonly causes mucosal infections such as otitis media, sinusitis, and bronchitis. We used a subtractive phage display approach to affinity select for peptides binding to the cell surface of a novel invasive NTHi strain R2866 (also called Int1). Over half of the selected phage peptides tested were bactericidal toward R2866 in a dose-dependent manner. Five of the clones encoded the same peptide sequence (KQRTSIRATEGCLPS; clone hi3/17), while the remaining four clones encoded unique peptides. All of the bactericidal phage peptides but one were cationic and had similar physical-chemical properties. Clone hi3/17 possessed a similar level of activity toward a panel of clinical NTHi isolates and
H. influenzae
type b strains but lacked bactericidal activity toward gram-positive (
Enterococcus faecalis
,
Staphylococcus aureus
) and gram-negative (
Proteus mirabilis
,
Pseudomonas aeruginosa
, and
Salmonella enterica
) bacteria. These data indicate that peptides binding to bacterial surface structures isolated by phage display may prove of value in developing new antibiotics.
Antimalarial Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors
Authors: Parikh Sunil , Gut Jiri , Istvan Eva , Goldberg Daniel E. , Havlir Diane V. , Rosenthal Philip J. 
Published: June 2005

ABSTRACT

Aspartic proteases play key roles in the biology of malaria parasites and human immunodeficiency virus type 1 (HIV-1). We tested the activity of seven HIV-1 protease inhibitors against cultured
Plasmodium falciparum
. All compounds inhibited the development of parasites at pharmacologically relevant concentrations. The most potent compound, lopinavir, was active against parasites (50% inhibitory concentration [IC
50
], 0.9 to 2.1 μM) at concentrations well below those achieved by ritonavir-boosted lopinavir therapy. Lopinavir also inhibited the
P. falciparum
aspartic protease plasmepsin II at a similar concentration (IC
50
, 2.7 μM). These findings suggest that use of HIV-1 protease inhibitors may offer clinically relevant antimalarial activity.
The Macrolide Roxithromycin Impairs NADPH Oxidase Activation and Alters Translocation of Its Cytosolic Components to the Neutrophil Membrane In Vitro
Authors: Abdelghaffar Houria , Babin-Chevaye Catherine , Labro Marie-Thérèse 
Published: June 2005

ABSTRACTWe have studied the interference of roxithromycin with NADPH oxidase, the key enzymatic system for oxidant production by human neutrophils. Roxithromycin alters the reconstitution of an active enzyme and impairs the translocation to the outer membrane of the cytosolic components p47-phox and p67-phox. Interestingly, in resting cells roxithromycin directly triggers the translocation of these factors without stimulating the oxidative burst.
In Vitro Interactions of Micafungin with Other Antifungal Drugs against Clinical Isolates of Four Species of
Cryptococcus
Authors: Serena Carolina , Fernández-Torres Belkys , Pastor F. Javier , Trilles Luciana , Lazéra Márcia dos Santos , Nolard Nicole , Guarro Josep 
Published: June 2005

ABSTRACT

The combination of micafungin (MFG) with amphotericin B (AMB), fluconazole, itraconazole, voriconazole, or ravuconazole was evaluated against 37 strains of four species of
Cryptococcus
by the checkerboard method. Antagonism was never seen. Synergy was observed for some isolates for each combination and was most frequent with MFG-AMB.