bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polycationic Peptides as Prophylactic Agents against Methicillin-Susceptible or Methicillin-Resistant
Staphylococcus epidermidis
Vascular Graft Infection
Authors: Giacometti Andrea , Cirioni Oscar , Ghiselli Roberto , Goffi Luigi , Mocchegiani Federico , Riva Alessandra , Scalise Giorgio , Saba Vittorio 
Published: July 2002

ABSTRACT

Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible
Staphylococcus epidermidis
and methicillin-resistant rifampin-susceptible
S. epidermidis
. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm
2
Dacron prostheses, followed by topical inoculation with 2 × 10
7
CFU of
S. epidermidis
. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.
Mutations in the Beginning of the
rpoB
Gene Can Induce Resistance to Rifamycins in both
Helicobacter pylori
and
Mycobacterium tuberculosis
Authors: Heep Markus , Rieger Ulrich , Beck Daniela , Lehn Norbert 
Published: July 2002

ABSTRACT

A clinical isolate of
Helicobacter pylori
that developed resistance to rifabutin during therapy carried an
rpoB
gene that retained a wild-type cluster region sequence but had acquired a novel codon 149 (V149F) mutation. In transformation experiments, the mutation was shown to confer high-level rifabutin resistance. The equivalent mutation (V176F) was present in several resistant isolates of
Mycobacterium tuberculosis
.
Identification of the Novobiocin Biosynthetic Gene Cluster of
Streptomyces spheroides
NCIB 11891
Authors: Steffensky Marion , Mühlenweg Agnes , Wang Zhao-Xin , Li Shu-Ming , Heide Lutz 
Published: July 2002

ABSTRACT

The novobiocin biosynthetic gene cluster from
Streptomyces spheroides
NCIB 11891 was cloned by using homologous deoxynucleoside diphosphate (dNDP)-glucose 4,6-dehydratase gene fragments as probes. Double-stranded sequencing of 25.6 kb revealed the presence of 23 putative open reading frames (ORFs), including the gene for novobiocin resistance,
gyrB
r
, and at least 11 further ORFs to which a possible role in novobiocin biosynthesis could be assigned. An insertional inactivation experiment with a dNDP-glucose 4,6-dehydratase fragment resulted in abolishment of novobiocin production, since biosynthesis of the deoxysugar moiety of novobiocin was blocked. Heterologous expression of a key enzyme of novobiocin biosynthesis, i.e., novobiocic acid synthetase, in
Streptomyces lividans
TK24 further confirmed the involvement of the analyzed genes in the biosynthesis of the antibiotic.
Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations
Authors: Conte John E. , Golden Jeffrey A. , McQuitty Mari , Kipps Juliana , Lin Emil T. , Zurlinden Elisabeth 
Published: July 2002

ABSTRACTEthionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean ± standard deviation [SD]) were 0.97 ± 0.65 and 0.65 ± 0.35 μg/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 ± 0.47 μg/ml) (P< 0.05). The concentration of ethionamide was significantly greater in ELF (5.63 ± 3.8 μg/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains ofMycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration ratios (mean ± SD) at 2 and 4 h were 8.7 ± 11.7 and 9.7 ± 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.
A Randomized Controlled Comparison of Azithromycin and Ofloxacin for Treatment of Multidrug-Resistant or Nalidixic Acid-Resistant Enteric Fever
Authors: Chinh Nguyen Tran , Parry Christopher M. , Ly Nguyen Thi , Ha Huynh Duy , Thong Mai Xuan , Diep To Song , Wain John , White Nicholas J. , Farrar Jeremy J. 
Published: July 2002

ABSTRACT

To examine the efficacy and safety of short courses of azithromycin and ofloxacin for treating multidrug-resistant (MDR, i.e., resistant to chloramphenicol, ampicillin, and cotrimoxazole) and nalidixic acid-resistant enteric fever, azithromycin (1 g once daily for 5 days at 20 mg/kg/day) and ofloxacin (200 mg orally twice a day for 5 days at 8 mg/kg/day) were compared in an open randomized study in adults admitted to a hospital with uncomplicated enteric fever. A total of 88 blood culture-confirmed patients were enrolled in the study (86 with
Salmonella enterica
serovar Typhi and 2 with
S. enterica
serovar Paratyphi A). Of these, 44 received azithromycin and 44 ofloxacin. A total of 68 of 87 (78%) isolates were MDR serovar Typhi, and 46 of 87 (53%) were nalidixic acid resistant. The MIC
90
(range) of azithromycin was 8 (4 to 16) μg/ml for the isolates. The MIC
90
(range) of ofloxacin for the nalidixic acid-sensitive isolates was 0.03 (0.015 to 0.06) μg/ml and for the nalidixic acid-resistant isolates it was 0.5 (0.25 to 1.0) μg/ml. There was no significant difference in the overall clinical cure rate with ofloxacin and azithromycin (38 of 44 [86.4%] versus 42 of 44 [95.5%];
P
= 0.27) or in the patients infected with nalidixic acid-resistant typhoid (17 of 21 [81.0%] versus 24 of 25 [96.0%];
P
= 0.16). However, patients with nalidixic acid-resistant typhoid treated with ofloxacin had a longer fever clearance time compared with those treated with azithromycin (174 [60 to 264] versus 135 [72 to 186] h;
P
= 0.004) and had positive fecal cultures after the end of treatment (7 of 17 [41%] versus 0 of 19 [0%];
P
= 0.002). Both antibiotics were well tolerated. A 5-day course of azithromycin was effective for the treatment of enteric fever due to MDR and nalidixic-acid-resistant serovar Typhi, whereas the ofloxacin regimen chosen was less satisfactory for these strains.
A
soxRS
-Constitutive Mutation Contributing to Antibiotic Resistance in a Clinical Isolate of
Salmonella enterica
(Serovar Typhimurium)
Authors: Koutsolioutsou Anastasia , Martins Elizabeth A. , White D. G. , Levy S. B. , Demple Bruce 
Published: July 2002

ABSTRACT

The
soxRS
regulon is activated by redox-cycling drugs such as paraquat and by nitric oxide. The >15 genes of this system provide resistance to both oxidants and multiple antibiotics. An association between clinical quinolone resistance and elevated expression of the
soxRS
regulon has been observed in
Escherichia coli
, but this association has not been explored for other enteropathogenic bacteria. Here we describe a
soxRS
-constitutive mutation in a clinical strain of
Salmonella enterica
(serovar Typhimurium) that arose with the development of resistance to quinolones during treatment. The elevated quinolone resistance in this strain derived from a point mutation in the
soxR
gene and could be suppressed in
trans
by multicopy wild-type
soxRS
. Multiple-antibiotic resistance was also transferred to a laboratory strain of
S. enterica
by introducing the cloned mutant
soxR
gene from the clinical strain. The results show that constitutive expression of
soxRS
can contribute to antibiotic resistance in clinically relevant
S. enterica.
Genetic Analyses of Mutations Contributing to Fluoroquinolone Resistance in Clinical Isolates of
Streptococcus pneumoniae
Authors: Weigel L. M. , Anderson G. J. , Facklam R. R. , Tenover F. C. 
Published: July 2002

ABSTRACT

Twenty-one clinical isolates of
Streptococcus pneumoniae
showing reduced susceptibility or resistance to fluoroquinolones were characterized by serotype, antimicrobial susceptibility, and genetic analyses of the quinolone resistance-determining regions (QRDRs) of
gyrA
,
gyrB
,
parC
, and
parE
. Five strains were resistant to three or more classes of antimicrobial agents. In susceptibility profiles for gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin, 14 isolates had intermediate- or high-level resistance to all fluoroquinolones tested except gemifloxacin (no breakpoints assigned). Fluoroquinolone resistance was not associated with serotype or with resistance to other antimicrobial agents. Mutations in the QRDRs of these isolates were more heterogeneous than those previously reported for mutants selected in vitro. Eight isolates had amino acid changes at sites other than ParC/S79 and GyrA/S81; several strains contained mutations in
gyrB
,
parE
, or both loci. Contributions to fluoroquinolone resistance by individual amino acid changes, including GyrB/E474K, ParE/E474K, and ParC/A63T, were confirmed by genetic transformation of
S. pneumoniae
R6. Mutations in
gyrB
were important for resistance to gatifloxacin but not moxifloxacin, and mutation of
gyrA
was associated with resistance to moxifloxacin but not gatifloxacin, suggesting differences in the drug-target interactions of the two 8-methoxyquinolones. The positions of amino acid changes within the four genes affected resistance more than did the total number of QRDR mutations. However, the effect of a specific mutation varied significantly depending on the agent tested. These data suggest that the heterogeneity of mutations will likely increase as pneumococci are exposed to novel fluoroquinolone structures, complicating the prediction of cross-resistance within this class of antimicrobial agents.
Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection
Authors: Jacobson Jeffrey M. , Feinman Lawrence , Liebes Leonard , Ostrow Nancy , Koslowski Victoria , Tobia Alfonso , Cabana Bernard E. , Lee Dong-Hun , Spritzler John , Prince Alfred M. 
Published: July 2002

ABSTRACTHypericin is a natural derivative of the common St. Johns wort plant,Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.
Differences in Antibiotic Resistance Patterns ofEnterococcus faecalisandEnterococcus faeciumStrains Isolated from Farm and Pet Animals
Authors: Butaye Patrick , Devriese Luc A. , Haesebrouck Freddy 
Published: July 2002

ABSTRACTThe prevalence of acquired resistance in 146Enterococcus faeciumand 166Enterococcus faecalisstrains from farm and pet animals, isolated in 1998 and 1999 in Belgium, against antibiotics used for growth promotion and for therapy was determined. Acquired resistance against flavomycin and monensin, two antibiotics used solely for growth promotion, was not detected. Avoparcin (glycopeptide) resistance was found sporadically inE. faeciumonly. Avilamycin resistance was almost exclusively seen in strains from farm animals. Resistance rates were higher inE. faeciumstrains from broiler chickens than in strains from other animal groups with tylosin and virginiamycin and inE. faecalisas well as inE. faeciumstrains with narasin and bacitracin. Resistance against ampicillin was mainly found amongE. faeciumstrains from pets and was absent inE. faecalis. Tetracycline resistance occurred most often in strains from farm animals, while enrofloxacin resistance, only found inE. faecalis, occurred equally among strains from all origins. Resistance against gentamicin was very rare in broiler strains, whereas resistance rates were high in strains from other origins. It can be concluded that resistance against antibiotics used solely for growth promotion was more prevalent inE. faeciumstrains than inE. faecalisstrains. With few exceptions, resistance against the different categories of antibiotics was more prevalent in strains from farm animals than in those from pets.
Limonene Arrests Parasite Development and Inhibits Isoprenylation of Proteins in
Plasmodium falciparum
Authors: Moura Ivan Cruz , Wunderlich Gerhard , Uhrig Maria L. , Couto Alicia S. , Peres Valnice J. , Katzin Alejandro M. , Kimura Emı́lia A. 
Published: July 2002

ABSTRACT

Isoprenylation is an essential protein modification in eukaryotic cells. Herein, we report that in
Plasmodium falciparum
, a number of proteins were labeled upon incubation of intraerythrocytic forms with either [
3
H]farnesyl pyrophosphate or [
3
H]geranylgeranyl pyrophosphate. By thin-layer chromatography, we showed that attached isoprenoids are partially modified to dolichol and other, uncharacterized, residues, confirming active isoprenoid metabolism in this parasite. Incubation of blood-stage
P. falciparum
treated with the isoprenylation inhibitor limonene significantly decreased the parasites' progression from the ring stage to the trophozoite stage and at 1.22 mM, 50% of the parasites died after the first cycle. Using Ras- and Rap-specific monoclonal antibodies, putative Rap and Ras proteins of
P. falciparum
were immunoprecipitated. Upon treatment with 0.5 mM limonene, isoprenylation of these proteins was significantly decreased, possibly explaining the observed arrest of parasite development.
Effects of Flavophospholipol on Resistance in Fecal
Escherichia coli
and Enterococci of Fattening P
Authors: van den Bogaard A. E. , Hazen M. , Hoyer M. , Oostenbach P. , Stobberingh E. E. 
Published: July 2002

ABSTRACT

A “plasmid-curing effect” of multiresistant
Escherichia coli
by flavophospholipol, an antibiotic used as an antimicrobial growth promoter (AMGP) in animal feeds, has been reported to occur in vitro and in vivo under experimental conditions. In this study, the effect of flavophospholipol under field conditions was studied. The prevalence and degree (proportion of resistant strains to the total numbers present per gram of feces) of resistance of indicator bacteria,
E. coli
and enterococci, was determined in fecal samples from three groups of pigs that were fed a commercial finisher feed without any AMGP. Group A was the negative control group without any AMGP, group B received the same feed with 9 mg of flavophospholipol/kg of feed (study group), and group C received the same feed with 15 mg of avoparcin/kg (positive control). Fecal samples from each pig were collected at the start and at the end of the study and assessed for the prevalence and degree of resistance against antibiotics commonly used either for therapy in pig medicine or as an AMGP. Before the start of the study, all pigs were colonized with multiresistant
E. coli
by mixing three resistant pig isolates through their feed after disturbance of the colonization resistance of the intestinal flora by a 3-day course of lincomycin and spectinomycin. At the end of the study, the overall prevalence and degree of resistance of
E. coli
in the fecal flora had increased significantly in groups A and C but remained at the same level as at the start of the study in group B. The prevalence of vancomycin resistance was 44 and 41% in groups A and B, respectively, but only very low numbers of vancomycin-resistant enterococci (VRE) per gram of feces were found. In the avoparcin-fed group, the prevalence was 72%, and in 57% of the samples, more than 50% of all enterococci present were vancomycin resistant. The prevalence of resistant
Enterococcus faecalis
increased only in the flavophospholipol-exposed group, from 23% before the start of the study to 43% at the end of the study. It was concluded that flavophospholipol effectively suppressed the augmentation and dissemination of multiresistant
E. coli
in the intestinal flora of fattening pigs. Avoparcin use strongly selected for VRE carriage and excretion. Therefore, as neither flavophospholipol nor any related molecule is used therapeutically, no cross-resistance with therapeutic antibiotics exists and no transmissible resistance has been shown; the major decrease in resistance in intestinal
E. coli
of flavophospholipol-fed animals seemed to outweigh the small increase in the risk of transfer of flavophospholipol-resistant
E. faecalis
from animals to humans via the food chain.
Evidence of Active Efflux in Resistance to Ciprofloxacin and to Ethidium Bromide by
Mycoplasma hominis
Authors: Raherison S. , Gonzalez P. , Renaudin H. , Charron A. , Bébéar C. , Bébéar C. M. 
Published: July 2002

ABSTRACT

The uptake of fluoroquinolones was characterized for the fluoroquinolone-susceptible strain PG21 of
Mycoplasma hominis
. Accumulation of fluoroquinolones appeared to occur by passive diffusion. Addition of arginine as the energizer significantly reduced the uptake of fluoroquinolones, suggesting the presence of an energy-dependent efflux process. Reserpine and orthovanadate, two multidrug pump inhibitors, increased significantly the ciprofloxacin (CIP) uptake. In contrast, such a strong effect was not observed for moxifloxacin and pefloxacin uptakes. Two ethidium bromide (EtBr)-resistant strains, selected in vitro, showed a resistance profile compatible with a multidrug-resistant phenotype, with increased MICs for the hydrophilic fluoroquinolones, CIP and norfloxacin, EtBr, and acriflavine. Taking the EtBr-resistant strain RB1La as a model, a significant decrease of the CIP and EtBr uptakes was observed compared to the reference strain PG21. In the presence of reserpine and orthovanadate, both inhibitors of ATP-dependent efflux pumps, the CIP uptake increased significantly, reaching approximately the same level as that of the susceptible strain. Similar results were obtained with EtBr uptake and efflux experiments. Our data suggest the presence of an active efflux system, possibly an ABC-type efflux pump, implicated in the resistance to CIP and unrelated compounds like EtBr in the human mycoplasma
M. hominis
.
Evolution of Thermotolerance in Hot Spring Cyanobacteria of the GenusSynechococcus
Authors: Miller Scott R. , Castenholz Richard W. 
Published: July 2002

ABSTRACTThe extension of ecological tolerance limits may be an important mechanism by which microorganisms adapt to novel environments, but it may come at the evolutionary cost of reduced performance under ancestral conditions. We combined a comparative physiological approach with phylogenetic analyses to study the evolution of thermotolerance in hot spring cyanobacteria of the genusSynechococcus. Among the 20 laboratory clones ofSynechococcusisolated from collections made along an Oregon hot spring thermal gradient, four different 16S rRNA gene sequences were identified. Phylogenies constructed by using the sequence data indicated that the clones were polyphyletic but that three of the four sequence groups formed a clade. Differences in thermotolerance were observed for clones with different 16S rRNA gene sequences, and comparison of these physiological differences within a phylogenetic framework provided evidence that more thermotolerant lineages ofSynechococcusevolved from less thermotolerant ancestors. The extension of the thermal limit in these bacteria was correlated with a reduction in the breadth of the temperature range for growth, which provides evidence that enhanced thermotolerance has come at the evolutionary cost of increased thermal specialization. This study illustrates the utility of using phylogenetic comparative methods to investigate how evolutionary processes have shaped historical patterns of ecological diversification in microorganisms.
Cloning and Random Mutagenesis of theErwinia herbicola tyrRGene for High-Level Expression of Tyrosine Phenol-Lyase
Authors: Katayama Takane , Suzuki Hideyuki , Koyanagi Takashi , Kumagai Hidehiko 
Published: July 2002

ABSTRACTTyrosine phenol-lyase (Tpl), which can synthesize 3,4-dihydroxyphenylalanine from pyruvate, ammonia, and catechol, is a tyrosine-inducible enzyme. Previous studies demonstrated that thetplpromoter ofErwinia herbicolais activated by the TyrR protein ofEscherichia coli. In an attempt to create a high-Tpl-expressing strain, we cloned thetyrRgene ofE. herbicolaand then randomly mutagenized it. Mutant TyrR proteins with enhanced ability to activatetplwere screened for by use of thelacreporter system inE. coli. The most increased transcription oftplwas observed for the strain with the mutanttyrRallele involving amino acid substitutions of alanine, cysteine, and glycine for valine-67, tyrosine-72, and glutamate-201, respectively. AtyrR-deficient derivative ofE. herbicolawas constructed and transformed with a plasmid carrying the mutanttyrRallele (V67A Y72C E201G substitutions). The resultant strain expressed Tpl without the addition of tyrosine to the medium and produced as much of it as was produced by the wild-type strain grown under tyrosine-induced conditions. The regulatory properties of the mutant TyrRV67A, TyrRY72C, TyrRE201G, and TyrRV67A Y72C E201Gproteins were examined in vivo. Interestingly, as opposed to the wild-type TyrR protein, the mutant TyrRV67Aprotein had a repressive effect on thetyrPpromoter in the presence of phenylalanine as the coeffector.