bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant
Staphylococcus aureus
Authors: Higgins Deborah L. , Chang Ray , Debabov Dmitri V. , Leung Joey , Wu Terry , Krause Kevin M. , Sandvik Erik , Hubbard Jeffrey M. , Kaniga Koné , Schmidt Donald E. , Gao Qiufeng , Cass Robert T. , Karr Dane E. , Benton Bret M. , Humphrey Patrick P. 
Published: February 2005

ABSTRACT

The emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms. As observed with vancomycin, telavancin inhibited late-stage peptidoglycan biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did the lipid II surrogate tripeptide
N
,
N
′-diacetyl-
l
-lysinyl-
d
-alanyl-
d
-alanine, with high affinity. Telavancin also perturbed bacterial cell membrane potential and permeability. In methicillin-resistant
Staphylococcus aureus
, telavancin caused rapid, concentration-dependent depolarization of the plasma membrane, increases in permeability, and leakage of cellular ATP and K
+
. The timing of these changes correlated with rapid , concentration-dependent loss of bacterial viability, suggesting that the early bactericidal activity of telavancin results from dissipation of cell membrane potential and an increase in membrane permeability. Binding and cell fractionation studies provided direct evidence for an interaction of telavancin with the bacterial cell membrane; stronger binding interactions were observed with the bacterial cell wall and cell membrane relative to vancomycin. We suggest that this multifunctional mechanism of action confers advantageous antibacterial properties.
Membrane Topology of the
Escherichia coli
AmpG Permease Required for Recycling of Cell Wall Anhydromuropeptides and AmpC β-Lactamase Induction
Authors: Chahboune Aicha , Decaffmeyer Marc , Brasseur Robert , Joris Bernard 
Published: February 2005

ABSTRACT

Escherichia coli
, and presumably most other gram-negative bacteria, possesses an efficient protein machinery for recycling its peptidoglycan during cell growth. The major recycled peptidoglycan product is
N
-acetylglucosamine-1,6-anhydro-
N
-acetylmuramic acid-tetrapeptide. Its uptake from the periplasm into the cytoplasm is carried out via the AmpG protein, an intrinsic membrane protein. In gram-negative bacteria carrying an
ampC
β-lactamase-inducible gene on their chromosomes, the induction mechanism is directly linked to peptidoglycan recycling. After identification of the different putative hydrophobic segments by computing, the AmpG topology was experimentally determined by using β-lactamase fusion. In the proposed model, AmpG contains 10 transmembrane segments and two large cytoplasmic loops.
Extended-Spectrum Beta-Lactamases among
Enterobacter
Isolates Obtained in Tel Aviv, Israel
Authors: Schlesinger Jacob , Navon-Venezia Shiri , Chmelnitsky Inna , Hammer-Münz Orly , Leavitt Azita , Gold Howard S. , Schwaber Mitchell J. , Carmeli Yehuda 
Published: February 2005

ABSTRACT

The extended-spectrum beta-lactamase (ESBL)-producing phenotype is frequent among
Enterobacter
isolates at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. We examined the clonal relatedness and characterized the ESBLs of a collection of these strains. Clonal relatedness was determined by pulsed-field gel electrophoresis. Isoelectric focusing (IEF) and transconjugation experiments were performed. ESBL gene families were screened by colony hybridization and PCR for
bla
TEM
,
bla
SHV
,
bla
CTX-M
,
bla
IBC
,
bla
PER
,
bla
OXA
,
bla
VEB
, and
bla
SFO
; and the PCR products were sequenced. The 17
Enterobacter
isolates studied comprised 15 distinct genotypes. All isolates showed at least one IEF band (range, one to five bands) whose appearance was suppressed by addition of clavulanate; pIs ranged from 5.4 to ≥8.2. Colony hybridization identified at least one family of beta-lactamase genes in 11 isolates: 10 harbored
bla
TEM
and 9 harbored
bla
SHV
. PCR screening and sequence analysis of the PCR products for
bla
TEM
,
bla
SHV
, and
bla
CTX-M
identified TEM-1 in 11 isolates, SHV-12 in 7 isolates, SHV-1 in 1 isolate, a CTX-M-2-like gene in 2 isolates, and CTX-M-26 in 1 isolate. In transconjugation experiments with four isolates harboring
bla
TEM-1
and
bla
SHV-12
, both genes were simultaneously transferred to the recipient strain
Escherichia coli
HB101. Plasmid mapping, PCR, and Southern analysis with TEM- and SHV-specific probes demonstrated that a single transferred plasmid carried both the TEM-1 and the SHV-12 genes. The widespread presence of ESBLs among
Enterobacter
isolates in Tel Aviv is likely due not to clonal spread but, rather, to plasmid-mediated transfer, at times simultaneously, of genes encoding several types of enzymes. The dominant ESBL identified was SHV-12.
Antiamoebic and Toxicity Studies of a Carbamic Acid Derivative and Its Therapeutic Effect in a Hamster Model of Hepatic Amoebiasis
Authors: Ordaz-Pichardo Cynthia , Shibayama Mineko , Villa-Treviño Saúl , Arriaga-Alba Myriam , Angeles Enrique , de la Garza Mireya 
Published: February 2005

ABSTRACT

Amoebiasis is an important public health problem in developing countries.
Entamoeba histolytica
, the causative agent of amoebiasis, may develop resistance to nitroimidazoles, a group of drugs considered to be the most effective against this parasitic disease. Therefore, research on new drugs for the treatment of this common infection still constitutes an important therapeutic demand. In the present study we determined the effects of a carbamate derivative, ethyl 4-chlorophenylcarbamate (C4), on trophozoites of
E. histolytica
strain HM-1:IMSS. C4 was subject to various toxicity tests, including the determination of mutagenicity for bacterial DNA and changes in the enzymatic activities of eukaryotic cells. Genotoxicity studies were performed by the mutagenicity Ames test (plate incorporation and preincubation methods) with
Salmonella enterica
serovar Typhimurium, with or without metabolic activation produced by the S9 fraction of rat liver. C4 toxicity studies were performed by measuring enzymatic activity in eukaryotic cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-formazan test with Fischer 344 rat hepatocytes. C4 did not induce either frame-shift mutations in
S. enterica
serovar Typhimurium TA97 or TA98 or base pair substitutions in strains TA100 and TA102. The compound was not toxic for cultured rat hepatic cells. Trophozoites treated with 100 μg of C4 per ml were inhibited 97.88% at 48 h of culture; moreover, damage to the amoebae was also confirmed by electron microscopy. The antiamoebic activity of C4 was evaluated by using an in vivo model of amoebic liver abscess in hamsters. Doses of 75 and 100 mg/100 g of body weight reduced the extent of the amoebic liver abscess by 84 and 94%, respectively. These results justify further studies to clearly validate whether C4 is a new suitable antiamoebic drug.
A Novel Engineered Peptide, a Narrow-Spectrum Antibiotic, is Effective against Vancomycin-Resistant
Enterococcus faecalis
Authors: Qiu Xiao-Qing , Zhang Jie , Wang He , Wu George Y. 
Published: February 2005

ABSTRACT

A novel antienterococcal peptide was prepared by fusing the enterococcal cCF10 pheromone to the channel-forming domain of colicin Ia, forming
Enterococcus faecalis
pheromonicin (PMC-EF). This peptide was bactericidal against vancomycin-resistant
Enterococcus faecalis
(VRE) organisms. Electron microscopy and vital dyes confirmed increased membrane permeability. All mice made bacteremic with VRE strains survived when they were treated with PMC-EF, while all controls died.
Deletion of the Multiple-Drug Efflux Pump AcrAB in
Escherichia
coli
Prolongs the Postantibiotic Effect
Authors: Stubbings William , Bostock Julieanne , Ingham Eileen , Chopra Ian 
Published: February 2005

ABSTRACT

The mechanism of the postantibiotic effect (PAE) was examined in
Escherichia
coli
. Drugs exhibited longer-lasting PAEs in an
acrAB
mutant, suggesting that intracellular drug concentrations influence the duration of the PAE. With specific assays for tetracycline and erythromycin, a direct link between intracellular persistence of antibiotics and maintenance of the PAE was established.
Inhaled Nitric Oxide Treatment of Patients with Pulmonary Tuberculosis Evidenced by Positive Sputum Smears
Authors: Long Richard , Jones Richard , Talbot James , Mayers Irvin , Barrie James , Hoskinson Michael , Light Bruce 
Published: February 2005

ABSTRACT
Endogenous nitric oxide (NO) has antimycobacterial properties. We tested the hypothesis that exogenous (inhaled) NO can be safely delivered and can accelerate airway disinfection for pulmonary tuberculosis patients treated with standard therapy. Exogenous NO administered at 80 ppm for 72 h can be safely delivered but does not accelerate airway disinfection.
mecA
Is Not Involved in the σ
B
-Dependent Switch of the Expression Phenotype of Methicillin Resistance in
Staphylococcus epidermidis
Authors: Knobloch Johannes K.-M. , Jäger Sebastian , Huck Jörn , Horstkotte Matthias A. , Mack Dietrich 
Published: February 2005

ABSTRACT

A lack of σ
B
activity reduces methicillin resistance in heterogeneous
Staphylococcus epidermidis
1057, whereas inactivation of the anti-sigma factor RsbW switched the phenotype to homogeneous expression of resistance. Oxacillin induction of
mecA
transcription is reduced in a σ
B
-negative strain. However,
mecA
is not involved in the switch of expression phenotype.
Synergistic Killing of
Streptococcus pneumoniae
with the Bacteriophage Lytic Enzyme Cpl-1 and Penicillin or Gentamicin Depends on the Level of Penicillin Resistance
Authors: Djurkovic Svetolik , Loeffler Jutta M. , Fischetti Vincent A. 
Published: February 2005

ABSTRACT

A combination of Cpl-1, a bacteriophage lytic enzyme, and penicillin, gentamicin, levofloxacin, or azithromycin was tested against
Streptococcus pneumoniae
strains with various susceptibilities to penicillin. Activities of Cpl-1 and gentamicin were increasingly synergistic with a decreasing penicillin MIC, while Cpl-1 and penicillin showed synergy against an extremely penicillin-resistant strain.
Molecular Epidemiology and Prevalence of Macrolide Efflux Genes
mef
(A) and
mef
(E) in
Streptococcus pneumoniae
Obtained in Canada from 1997 to 2002
Authors: Wierzbowski Aleksandra K. , Swedlo Dean , Boyd Dave , Mulvey Michael , Nichol Kim A. , Hoban Daryl J. , Zhanel George G. 
Published: February 2005

ABSTRACT

One hundred forty M phenotype
Streptococcus pneumoniae
isolates were evaluated by PCR-restriction fragment length polymorphism, serotyping, and pulsed-field gel electrophoresis. Molecular genotyping revealed that the predominant macrolide resistance mechanism in
S. pneumoniae
in Canada is
mef
(E) and resistance dissemination is due to both spread of the genetic element MEGA as well as clonal dissemination of penicillin- and/or macrolide-resistant strains.
Bactericidal Effects of Toluidine Blue-Mediated Photodynamic Action on
Vibrio vulnificus
Authors: Wong Tak-Wah , Wang Yin-Yi , Sheu Hamm-Ming , Chuang Yin-Ching 
Published: February 2005

ABSTRACT

Vibrio vulnificus
is a gram-negative, highly invasive bacterium responsible for human opportunistic infections. We studied the antibacterial effects of toluidine blue O (TBO)-mediated photodynamic therapy (PDT) for
V. vulnificus
wound infections in mice. Fifty-three percent (10 of 19) of mice treated with 100 μg of TBO per ml and exposed to broad-spectrum red light (150 J/cm
2
at 80 mW/cm
2
) survived, even though systemic septicemia had been established with a bacterial inoculum 100 times the 50% lethal dose. In vitro, the bacteria were killed after exposure to a lower light dose (100 J/cm
2
at 80 mW/cm
2
) in the presence of low-dose TBO (0.1 μg/ml). PDT severely damaged the cell wall and reduced cell motility and virulence. Cell-killing effects were dependent on the TBO concentration and light doses and were mediated partly through the reactive oxygen species generated during the photodynamic reaction. Our study has demonstrated that PDT can cure mice with otherwise fatal
V. vulnificus
wound infections. These promising results suggest the potential of this regimen as a possible alternative to antibiotics in future clinical applications.
Global Expression of Prophage Genes in
Escherichia coli
O157:H7 Strain EDL933 in Response to Norfloxacin
Authors: Herold Sylvia , Siebert Jutta , Huber Andrea , Schmidt Herbert 
Published: February 2005

ABSTRACT

We investigated the influence of a low concentration of the gyrase inhibitor norfloxacin on the transcriptome of enterohemorrhagic
Escherichia coli
O157:H7 strain EDL933. For this purpose, we used a commercial DNA microarray containing oligonucleotides specific for
E. coli
O157:H7 strains EDL933 and RIMD0509952 and
E. coli
K-12 strain MG1655. Under the conditions applied, 5,963 spots (94% of all spots) could be analyzed. Among these, 118 spots (
P
< 0.05) indicated transcriptional upregulation and 122 spots (
P
< 0.05) indicated transcriptional downregulation of the
E. coli
genes present on the array. Eighty-five upregulated EDL933 genes were phage borne. Fifty-two of them could be ascribed to the Shiga toxin-encoding phages (Stx phages) BP-933W and CP-933V; the other 33 genes belonged to non-Stx prophage elements in the EDL933 genome. Genes present in the BP-933W prophage genome were induced most strongly up to 158-fold in the case of

stxA
2

upon induction with norfloxacin. Twenty-two additional upregulated genes appeared to be
E. coli
O157:H7 strain RIMD0509952-specific phage elements, and the remaining 11 genes were related mainly to recombination and stress functions. Downregulation was indicated predominantly for genes responsible for bacterial primary metabolism, such as energy production, cell division, and amino acid biosynthesis. Interestingly, some genes present in the locus of enterocyte effacement appeared to be downregulated. The results of the study have shown that a low concentration of norfloxacin has profound effects on the transcriptome of
E. coli
O157:H7.
Open-Label, Dose Escalation Study of the Safety and Pharmacokinetic Profile of Tefibazumab in Healthy Volunteers
Authors: Reilley Sandra , Wenzel Eric , Reynolds Laurie , Bennett Beth , Patti Joseph M. , Hetherington Seth 
Published: February 2005

ABSTRACT

Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of
Staphylococcus aureus
infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (
C
max
) of 59, 127, 252, and 492 μg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (
T
max
) was 1.0 h for each dose. The mean elimination half-life (
t
1/2
) was approximately 22 days. The volume of distribution (
V
) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 μg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 μg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.
Pulmonary Damage and Bacterial Load in Assessment of the Efficacy of Simulated Human Treatment-Like Amoxicillin (2,000 Milligrams) Therapy of Experimental Pneumococcal Pneumonia Caused by Strains for Which Amoxicillin MICs Differ
Authors: Gracia Matilde , Martínez-Marín Carmina , Huelves Lorena , Giménez Maria J. , Aguilar Lorenzo , Carcas Antonio , Ponte Carmen , Soriano Francisco 
Published: February 2005

ABSTRACT

An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, ≤0.015 and 2 μg/ml) and two non-amoxicillin-susceptible (MIC, 4 μg/ml)
Streptococcus pneumoniae
strains was developed for testing the efficacy of amoxicillin administered to simulate human serum kinetics after treatment with amoxicillin-clavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5 days). The end points for efficacy were reductions in bacterial loads in the lungs and reductions in levels of pulmonary damage. For the amoxicillin-susceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log
10
CFU/pair of lungs was obtained, and the time for which the serum antibiotic concentration (SAC) was higher than the MIC (
T
S
A
C
>
MIC
) was greater than 60% of the dosing interval. For non-amoxicillin-susceptible strains, the decrease in bacterial load was 1.34 to 1.75 log
10
CFU/pair of lungs, with a
T
S
A
C
>
MIC
of 46.7% of the dosing interval. An in vitro study showed that serotype 9V non-amoxicillin-susceptible strains behaved as tolerant-like to concentrations similar to those in the in vivo model. The high and maintained SACs (
T
S
A
C
>
MIC
, >46% for all strains) significantly diminished lung injury (affected area of the lung and lung weight), compared to that in controls, by all strains, regardless of the MIC, bactericidal behavior in in vitro killing curves, or the serotype of the infecting strain. These results show the importance of host therapeutic end points in the evaluation of antibiotic efficacy. The antibiotic was more efficacious, for one nonsusceptible strain tested, when the treatment was started early (1 h postinoculation [p.i.]) than when treatment was delayed (24 h p.i.).
Biological risk indicators for recurrent non-specific low back pain in adolescents
Authors: Jones M A , Stratton G , Reilly T , Unnithan V B 
Published: February 2005

Objectives:A matched case-control study was carried out to evaluate biological risk indicators for recurrent non-specific low back pain in adolescents.Methods:Adolescents with recurrent non-specific low back pain (symptomatic; n  =  28; mean (SD) age 14.9 (0.7) years) and matched controls (asymptomatic; n  =  28; age 14.9 (0.7) years) with no history of non-specific low back pain participated. Measures of stature, mass, sitting height, sexual maturity (Tanner self assessment), lateral flexion of the spine, lumbar sagittal plane mobility (modified Schöber), hip range of motion (Leighton flexometer), back and hamstring flexibility (sit and reach), and trunk muscle endurance (number of sit ups) were performed using standardised procedures with established reliability. Backward stepwise logistic regression analysis was performed, with the presence/absence of recurrent low back pain as the dependent variable and the biological measures as the independent variables.Results:Hip range of motion, trunk muscle endurance, lumbar sagittal plane mobility, and lateral flexion of the spine were identified as significant risk indicators of recurrent low back pain (p<0.05). Follow up analysis indicated that symptomatic subjects had significantly reduced lateral flexion of the spine, lumbar sagittal plane mobility, and trunk muscle endurance (p<0.05).Conclusions:Hip range of motion, abdominal muscle endurance, lumbar flexibility, and lateral flexion of the spine were risk indicators for recurrent non-specific low back pain in a group of adolescents. These risk indicators identify the potential for exercise as a primary or secondary prevention method.
Participation in leanness sports but not training volume is associated with menstrual dysfunction: a national survey of 1276 elite athletes and controls
Authors: Torstveit M K , Sundgot-Borgen J 
Published: February 2005

Objective:To examine the prevalence of menstrual dysfunction in the total population of Norwegian elite female athletes and national representative controls in the same age group.Methods:A detailed questionnaire that included questions on training and/or physical activity patterns, menstrual, dietary, and weight history, oral contraceptive use, and eating disorder inventory subtests was administered to all elite female athletes representing the country at the junior or senior level (aged 13–39 years, n  =  938) and national representative controls in the same age group (n  =  900). After exclusion, a total of 669 athletes (88.3%) and 607 controls (70.2%) completed the questionnaire satisfactorily.Results:Age at menarche was significantly (p<0.001) later in athletes (13.4 (1.4) years) than in controls (13.0 (1.3) years), and differed among sport groups. A higher percentage of athletes (7.3%) than controls (2.0%) reported a history of primary amenorrhoea (p<0.001). A similar percentage of athletes (16.5%) and controls (15.2%) reported present menstrual dysfunction, but a higher percentage of athletes competing in leanness sports reported present menstrual dysfunction (24.8%) than athletes competing in non-leanness sports (13.1%) (p<0.01) and controls (p<0.05).Conclusions:These novel data include virtually all eligible elite athletes, and thus substantially extend previous studies. Age at menarche occurred later and the prevalence of primary amenorrhoea was higher in elite athletes than in controls. A higher percentage of athletes competing in sports that emphasise thinness and/or a specific weight reported present menstrual dysfunction than athletes competing in sports focusing less on such factors and controls. On the basis of a comparison with a previous study, the prevalence of menstrual dysfunction was lower in 2003 than in 1993.
Enhancing the efficacy of the 20 m multistage shuttle run test
Authors: Flouris A D , Metsios G S , Koutedakis Y 
Published: February 2005

Objective:Maximal oxygen uptake (Vo2max) of 44 ml kg−1min−1is an accepted criterion (Vo2CR) below which health and fitness for young male adults may be compromised. New algorithms validated for Vo2CRscreening using the 20 m multistage shuttle run test (20mMST) were developed.Methods:Vo2maxwas assessed in 110 males using a stationary gas analyser in a treadmill test (TT) and in 40 of these subjects using a portable gas analyser in the 20mMST. Vo2maxpredicted from the 20mMST in 70 subjects was used for cross validation. Two equations predicting Vo2maxduring 20mMST (EQMST) and TT (EQTT) were developed.Results:Significant energy cost variance (ECV) was detected between TT and 20mMST (p<0.001), correlated significantly with subject height, and was a significant predictor of Vo2maxdifferences between TT and 20mMST. Ther2of EQMSTwas 0.92 (p<0.001). Predicted Vo2maxvalues from EQMSTcorrelated with directly measured 20mMST Vo2maxatr = 0.96 (p<0.001). ANOVA detected no mean difference (p>0.05) between predicted and measured values. Prevalence of low fitness based on Vo2CRwas 0.37. McNemar χ2indicated significant differences in sensitivity (p<0.001) and specificity (p<0.05) between the original 20mMST equation (EQLÉG) and EQTT, regarding Vo2CRscreening. Cohen’s κ demonstrated higher agreement with TT Vo2maxfor EQTT(p<0.001) than EQLÉG(p<0.05). TT Vo2maxcorrelated with the end result of both EQLÉGand EQTTatr = 0.75 (p<0.001). Unlike EQTT(p>0.05), mean predicted Vo2maxfrom EQLÉGwas significantly higher compared to TT Vo2max(p<0.001).Conclusion:These algorithms increase the efficacy of 20mMST to accurately evaluate aspects of health and fitness.