bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Class of Genetic Element, Staphylococcus Cassette Chromosome
mec
, Encodes Methicillin Resistance in
Staphylococcus aureus
Authors: Katayama Y. , Ito T. , Hiramatsu K. 
Published: July 2002

ABSTRACT

We have previously shown that the methicillin-resistance gene
mecA
of
Staphylococcus aureus
strain N315 is localized within a large (52-kb) DNA cassette (designated the staphylococcal cassette chromosome
mec
[SCC
mec
]) inserted in the chromosome. By sequence determination of the entire DNA, we identified two novel genes (designated cassette chromosome recombinase genes [
ccrA
and
ccrB
]) encoding polypeptides having a partial homology to recombinases of the invertase/resolvase family. The open reading frames were found to catalyze precise excision of the SCC
mec
from the methicillin-resistant
S. aureus
chromosome and site-specific as well as orientation-specific integration of the SCC
mec
into the
S. aureus
chromosome when introduced into the cells as a recombinant multicopy plasmid. We propose that SCC
mec
driven by a novel set of recombinases represents a new family of staphylococcal genomic elements.
Ineffectiveness of Echinacea for Prevention of Experimental Rhinovirus Colds
Authors: Turner Ronald B. , Riker Donald K. , Gangemi J. David 
Published: July 2002

ABSTRACT
The purpose of this study was to assess the effectiveness of echinacea for the prevention of experimental rhinovirus colds. Infection occurred in 44 and 57% and illness occurred in 36 and 43% of the echinacea- and placebo-treated subjects, respectively. This preparation of echinacea had no significant effect on either the occurrence of infection or the severity of illness.
Cloning and Sequence of the Gene Encoding a Novel Cefotaxime-Hydrolyzing β-Lactamase (CTX-M-9) from
Escherichia coli
in Spain
Authors: Sabaté Montserrat , Tarragó Raül , Navarro Ferran , Miró Elisenda , Vergés Clara , Barbé Jordi , Prats Guillermo 
Published: July 2002

ABSTRACT

A new CTX-M-type β-lactamase (CTX-M-9) has been cloned from a clinical cefotaxime-resistant
Escherichia coli
strain. Despite the close identity that exists between the CTX-M-9 and Toho-2 β-lactamases (88%), the 35 amino acids located between residues Ala-185 and Ala-219 are totally different in both enzymes. Outside of this region there are only six amino acids substitutions between both proteins.
A Double-Blind Placebo-Controlled Crossover Trial of Intravenous Magnesium Sulfate for Foscarnet-Induced Ionized Hypocalcemia and Hypomagnesemia in Patients with AIDS and Cytomegalovirus Infection
Authors: Huycke Mark M. , Naguib M. Tarek , Stroemmel Mathias M. , Blick Kenneth , Monti Katherine , Martin-Munley Sarah , Kaufman Chris 
Published: July 2002

ABSTRACT

Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to treat cytomegalovirus disease in immunocompromised patients. One common side effect is acute ionized hypocalcemia and hypomagnesemia following intravenous administration. Foscarnet-induced ionized hypomagnesemia might contribute to ionized hypocalcemia by impairing excretion of preformed parathyroid hormone (PTH) or by producing target organ resistance. Prevention of ionized hypomagnesemia following foscarnet administration could blunt the development of ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the decline in ionized calcium and/or magnesium following foscarnet infusions, MgSO
4
at doses of 1, 2, and 3 g was administered in a double-blind, placebo-controlled, randomized, crossover trial to 12 patients with AIDS and cytomegalovirus disease. Overall, increasing doses of MgSO
4
reduced or eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation, however, had no discernible effect on foscarnet-induced ionized hypocalcemia despite significant increases in serum PTH levels. No dose-related, clinically significant adverse events were found, suggesting that intravenous supplementation with up to 3 g of MgSO
4
was safe in this chronically ill population. Since parenteral MgSO
4
did not alter foscarnet-induced ionized hypocalcemia or symptoms associated with foscarnet, routine intravenous supplementation for patients with normal serum magnesium levels is not recommended during treatment with foscarnet.
Human Immunodeficiency Virus Type 1 Mutations Selected in Patients Failing Efavirenz Combination Therapy
Authors: Bacheler Lee T. , Anton Elizabeth D. , Kudish Phil , Baker David , Bunville Julie , Krakowski Karen , Bolling Laura , Aujay Monette , Wang Xin Victoria , Ellis Dawn , Becker Mary F. , Lasut Amy L. , George Henry J. , Spalding Daniel R. , Hollis Greg , Abremski Kenneth 
Published: July 2002

ABSTRACT
Efavirenz is a potent and selective nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Nucleotide sequence analyses of the protease and RT genes (coding region for amino acids 1 to 229) of multiple cloned HIV-1 genomes from virus found in the plasma of patients in phase II clinical studies of efavirenz combination therapy were undertaken in order to identify the spectrum of mutations in plasma-borne HIV-1 associated with virological treatment failure. A K103N substitution was the HIV-1 RT gene mutation most frequently observed among plasma samples from patients for whom combination therapy including efavirenz failed, occurring in at least 90% of cases of efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC) treatment failure. V108I and P225H mutations were observed frequently, predominantly in viral genomes that also contained other nonnucleoside RT inhibitor (NNRTI) resistance mutations. L100I, K101E, K101Q, Y188H, Y188L, G190S, G190A, and G190E mutations were also observed. V106A, Y181C, and Y188C mutations, which have been associated with high levels of resistance to other NNRTIs, were rare in the patient samples in this study, both before and after exposure to efavirenz. The spectrum of mutations observed in cases of virological treatment failure was similar for patients initially dosed with efavirenz at 200, 400, or 600 mg once a day and for patients treated with efavirenz in combination with indinavir, stavudine, or ZDV-3TC. The proportion of patients carrying NNRTI resistance mutations, usually K103N, increased dramatically at the time of initial viral load rebound in cases of treatment failure after exposure to efavirenz. Viruses with multiple, linked NNRTI mutations, especially K103N-V108I and K103N-P225H double mutants, accumulated more slowly following the emergence of K103N mutant viruses.
Effect of Xylitol on Growth of
Streptococcus pneumoniae
in the Presence of Fructose and Sorbitol
Authors: Tapiainen Terhi , Kontiokari Tero , Sammalkivi Laura , Ikäheimo Irma , Koskela Markku , Uhari Matti 
Published: July 2002

ABSTRACT

Xylitol is effective in preventing acute otitis media by inhibiting the growth of
Streptococcus pneumoniae
. To clarify this inhibition we used fructose, which is known to block similar growth inhibition observed in
Streptococcus mutans
. In addition, we evaluated the efficacy of sorbitol in inhibiting the growth of pneumococci, as sorbitol is widely used for indications similar to those for which xylitol is used. The addition of 5% xylitol to the growth medium resulted in marked growth inhibition, an effect which was totally eliminated in the presence of 1, 2.5, or 5% fructose but not in the presence of 1 or 5% glucose, 1% galactose, or 1% sucrose. This finding implies that xylitol-induced inhibition of pneumococcal growth is mediated via the fructose phosphotransferase system in a way similar to that in which mutans group streptococcal growth is inhibited. The addition of sorbitol at concentrations of 1, 2.5, or 5% to the growth medium did not affect the growth of pneumococci and neither inhibited nor enhanced the xylitol-induced growth impairment. Thus, it seems that xylitol is the only commercially used sugar substitute proven to have an antimicrobial effect on pneumococci.
Affinities of β-Lactams for Penicillin Binding Proteins of
Chlamydia trachomatis
and Their Antichlamydial Activities
Authors: Storey Christopher , Chopra Ian 
Published: July 2002

ABSTRACT

Binding affinities of β-lactam antibiotics for the three penicillin binding proteins (PBPs) from
Chlamydia trachomatis
were determined in vitro and compared with their antichlamydial activities. Mecillinam selectively inhibited PBP1, with a 50% inhibitory concentration for PBP1 binding (0.2 μg/ml) similar to the MIC (0.1 μg/ml) and minimum bactericidal concentration (0.25 μg/ml). Although the other β-lactams inhibited a wider range of PBPs than mecillinam, their antichlamydial activities were inferior to that of mecillinam.
A MATE Family Multidrug Efflux Transporter Pumps out Fluoroquinolones in
Bacteroides thetaiotaomicron
Authors: Miyamae Shin , Ueda Ohmi , Yoshimura Fuminobu , Hwang Jaiweon , Tanaka Yoshinobu , Nikaido Hiroshi 
Published: July 2002

ABSTRACT

We cloned a gene,
bexA
, that codes for a multidrug efflux transporter from the chromosomal DNA of
Bacteroides thetaiotaomicron
ATCC 29741 by using an
Escherichia coli
Δ
acrAB
Δ
acrEF
mutant as a host. Although the initial recombinant construct contained other open reading frames, the presence of
bexA
alone was sufficient to confer to the
E. coli
host elevated levels of resistance to norfloxacin, ciprofloxacin, and ethidium bromide. Disruption of
bexA
in
B. thetaiotaomicron
made the strain more susceptible to norfloxacin, ciprofloxacin, and ethidium bromide, showing that this gene is expressed in this organism and functions as a multidrug efflux pump. The deduced BexA protein sequence was homologous to the protein sequence of
Vibrio parahaemolyticus
NorM, a multidrug efflux transporter, and thus, BexA belongs to the multidrug and toxic compound extrusion (MATE) family.
Glutathione-Induced Conversion of Pentavalent Antimony to Trivalent Antimony in Meglumine Antimoniate
Authors: Frézard Frédéric , Demicheli Cynthia , Ferreira Claúdio S. , Costa Michelle A. P. 
Published: July 2002

ABSTRACT

The standard treatment of human leishmaniases involves the use of pentavalent antimony [Sb(V)] compounds, including meglumine antimoniate. The mode of action of these compounds has not been fully elucidated. The possibility that Sb(III) is involved has been suggested; however, the biomolecule that may induce the conversion of Sb(V) to Sb(III) has not yet been identified. In the present study, we investigated both the ability of reduced glutathione (GSH) to promote the reduction of Sb(V) into Sb(III) in meglumine antimoniate and the effects of pH and temperature on this transformation. GSH did promote the reduction of Sb(V) into Sb(III) in a dose-dependent manner. When GSH and meglumine antimoniate were incubated together at a GSH/Sb molar ratio superior or equal to 5:1, all antimony was encountered in the reduced form, indicating a stoichiometry of 5:1 between GSH and Sb(V) in the reaction. The reaction between Sb(V) and GSH was favored at an acidic pH (pH 5) and an elevated temperature (37°C), conditions found within the phagolysosome, in which
Leishmania
resides. For instance, about 30% of the Sb(V) (concentration, 2mM) was converted to Sb(III) following incubation for 3 days with 10 mM GSH at pH 5 and 37°C. Our data support the hypothesis that Sb(V) would be converted by GSH, or a related thiol compound, to more toxic Sb(III) in the phagolysosome of macrophages.
High-Dose Intravenous Ribavirin Therapy for Subacute Sclerosing Panencephalitis
Authors: Hosoya Mitsuaki , Shigeta Shiro , Mori Shuichi , Tomoda Akemi , Shiraishi Seiji , Miike Teruhisa , Suzuki Hitoshi 
Published: July 2002

ABSTRACT
Two patients with subacute sclerosing panencephalitis (SSPE) were treated safely and effectively with high doses of intravenous ribavirin combined with intraventricular alpha interferon. The ribavirin concentrations maintained in the serum and cerebrospinal fluid were higher than those which inhibit SSPE virus replication in vitro and in vivo.
Resistance Studies with Daptomycin
Authors: Silverman Jared A. , Oliver Nicole , Andrew Ted , Li Tongchuan 
Published: July 2002

ABSTRACT

We studied the in vitro emergence of resistance to daptomycin using three methods: spontaneous resistance incidence, serial passage in the presence of increasing drug concentrations, and chemical mutagenesis. No spontaneously resistant mutants were obtained for any organism tested (<10
−10
for
Staphylococcus aureus
, <10
−9
for
Staphylococcus epidermidis
, <10
−9
for
Enterococcus faecalis
, <10
−9
for
Enterococcus faecium
, <10
−8
for
Streptococcus pneumoniae
). Population analysis demonstrated that bacterial susceptibility to daptomycin is heterogeneous. Assay results were sensitive to calcium concentration and culture density, both of which can affect apparent resistance rates. Stable
S. aureus
mutants were isolated by both serial passage in liquid media and chemical mutagenesis. The daptomycin MICs for these isolates were 8- to 32-fold higher than for the parental strain. Many mutants with high MICs (>12.5 μg/ml) had significant growth defects but did not display phenotypes typical of
S. aureus
small colony variants. The voltage component (Δψ) of the bacterial membrane potential was increased in three independent resistant isolates. In vivo data showed that some daptomycin-resistant mutants had lost significant virulence. For other mutants, the degree of in vitro resistance was greater than the change in in vivo susceptibility. These results suggest that infection with some daptomycin-resistant organisms may still be easily treatable.
Interaction between DNA Gyrase and Quinolones: Effects of Alanine Mutations at GyrA Subunit Residues Ser
83
and Asp
87
Authors: Barnard Faye M. , Maxwell Anthony 
Published: July 2002

ABSTRACT

DNA gyrase is a target of quinolone antibacterial agents, but the molecular details of the quinolone-gyrase interaction are not clear. Quinolone resistance mutations frequently occur at residues Ser
83
and Asp
87
of the gyrase A subunit, suggesting that these residues are involved in drug binding. Single and double alanine substitutions were created at these positions (Ala
83
, Ala
87
, and Ala
83
Ala
87
), and the mutant proteins were assessed for DNA supercoiling, DNA cleavage, and resistance to a number of quinolone drugs. The Ala
83
mutant was fully active in supercoiling, whereas the Ala
87
and the double mutant were 2.5- and 4- to 5-fold less active, respectively; this loss in activity may be partly due to an increased affinity of these mutant proteins for DNA. Supercoiling inhibition and cleavage assays revealed that the double mutant has a high level of resistance to certain quinolones while the mutants with single alanine substitutions show low-level resistance. Using a drug-binding assay we demonstrated that the double-mutant enzyme-DNA complex has a lower affinity for ciprofloxacin than the wild-type complex. Based on the pattern of resistance to a series of quinolones, an interaction between the C-8 group of the quinolone and the double-mutant gyrase in the region of residues 83 and 87 is proposed.
DNA Gyrase-Mediated Natural Resistance to Fluoroquinolones in
Ehrlichia
spp
Authors: Maurin M. , Abergel C. , Raoult D. 
Published: July 2002

ABSTRACT

Fluoroquinolone susceptibility heterogeneity between various
Ehrlichia
species has been previously demonstrated. In gram-negative bacteria, resistance to fluoroquinolones most often corresponds to specific amino acid variations in a portion of the protein sequence of the A subunit of DNA gyrase (GyrA), referred to as the quinolone resistance-determining region (QRDR). We suspected a similar mechanism to be responsible for natural resistance in some
Ehrlichia
species. To verify this hypothesis, we sequenced the entire
gyrA
gene of the quinolone-susceptible species
Ehrlichia sennetsu
and designed specific primers to amplify and sequence the QRDR of four other
Ehrlichia
species as well as the closely related species
Cowdria ruminantium
. We identified in the fluoroquinolone-resistant species
Ehrlichia chaffeensis
and
Ehrlichia canis
a specific GyrA QRDR amino acid sequence, also present in
C. ruminantium
(whose susceptibility to fluoroquinolones remains unknown). These three species belong to a single phylogenetic cluster referred to as the
E. canis
genogroup. A different GyrA QRDR pattern, shared by the
Ehrlichia
species representatives of the
E. sennetsu
and
Ehrlichia phagocytophila
genogroups, was identified. Three of the four species tested are known to be susceptible to fluoroquinolones. A serine residue in position 83 (
Escherichia coli
numbering) in the susceptible species is replaced by an alanine residue in fluoroquinolone-resistant species. These results are consistent with the current knowledge on fluoroquinolone resistance in other gram-negative bacteria. They are indicative of a natural gyrase-mediated resistance to fluoroquinolones in the
E. canis
genogroup.
Novel Class A β-Lactamase Sed-1 from
Citrobacter sedlakii
: Genetic Diversity of β-Lactamases within the
Citrobacter
Genus
Authors: Petrella Stephanie , Clermont Dominique , Casin Isabelle , Jarlier Vincent , Sougakoff Wladimir 
Published: July 2002

ABSTRACT

Citrobacter sedlakii
2596, a clinical strain resistant to aminopenicillins, carboxypenicillins, and early cephalosporins such as cephalothin, but remaining susceptible to acylureidopenicillins, carbapenems, and later cephalosporins such as cefotaxime, was isolated from the bile of a patient treated with β-lactam and quinolone antibiotics. The isolate produced an inducible class A β-lactamase of pI 8.6, named Sed-1, which was purified. Characterized by a molecular mass of 30 kDa, Sed-1 preferentially hydrolyzed benzylpenicillin, cephalothin, and cloxacillin. The corresponding gene,
bla
Sed-1
, was cloned and sequenced. Its deduced amino acid sequence shared more than 60% identity with the chromosome-encoded β-lactamases from
Citrobacter koseri
(formerly
C. diversus
) (84%),
Klebsiella oxytoca
(74%),
Serratia fonticola
(67%), and
Proteus vulgaris
(63%) and 71% identity with the plasmid-mediated enzyme MEN-1. A gene coding for a LysR transcriptional regulator was found upstream from
bla
Sed-1
. This regulator, named SedR, displayed 90% identity with the AmpR sequence of the chromosomal β-lactamase from
C. koseri
and 63 and 50% identity with the AmpR sequences of
P. vulgaris
and
Enterobacter cloacae
, respectively. By using DNA-DNA hybridization, a
bla
Sed-1
-like gene was identified in two reference strains,
C. sedlakii
(CIP-105037) and
Citrobacter rodentium
(CIP-104675), but not in the 18 strains of
C. koseri
studied. Two DNA fragments were amplified and sequenced from the reference strains of
C. sedlakii
CIP-105037 and
C. rodentium
CIP-104675 using two primers specific for
bla
Sed-1
. They shared 98 and 80% identity with
bla
Sed-1
, respectively, confirming the diversity of the chromosomally encoded class A β-lactamases found in
Citrobacter
.
Once-Daily Oral Gatifloxacin versus Oral Levofloxacin in Treatment of Uncomplicated Skin and Soft Tissue Infections: Double-Blind, Multicenter, Randomized Study
Authors: Tarshis Gary A. , Miskin Barry M. , Jones Terry M. , Champlin John , Wingert Kevin J. , Breen Jeanne D. , Brown Michael J. 
Published: July 2002

ABSTRACTThis was a double-blind, multicenter study in which 410 adults (≥18 years of age) with uncomplicated skin and soft tissue infections (SSTIs) were randomized to receive either 400 mg of gatifloxacin orally once daily or 500 mg of levofloxacin orally once daily for 7 to 10 days. The study protocol called for four assessments—before and during treatment, at the end of treatment, and posttreatment. Efficacy evaluations included clinical response and bacterial eradication rates. Of 407 treated patients, 202 (108 women, 94 men) received gatifloxacin and 205 (111 women, 94 men) received levofloxacin. For clinically evaluable patients, the cure rates were 91% for gatifloxacin and 84% for levofloxacin (95% confidence interval [CI] for the difference, −2.0 to 15.2%). Clinical cure rates for microbiologically evaluable patients were 93% for gatifloxacin and 88% for levofloxacin (95% CI for the difference, −6.5 to 16.8%). The bacterial eradication rate was 92% for each group, with gatifloxacin eradicating 93% of the methicillin-susceptibleStaphylococcus aureusisolates and levofloxacin eradicating 91% of them. Both drugs were well tolerated. Most of the adverse events were mild to moderate, and nausea was the most common adverse event in each treatment arm. Once-daily oral gatifloxacin (400 mg) is clinically efficacious and well tolerated compared with once-daily levofloxacin (500 mg) for the treatment of patients with uncomplicated SSTIs.
Specific Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Integration in Cell Culture: Putative Inhibitors of HIV-1 Integrase
Authors: Vandegraaff Nick , Kumar Raman , Hocking Helen , Burke Terrence R. , Mills John , Rhodes David , Burrell Christopher J. , Li Peng 
Published: July 2002

ABSTRACTTo study the effect of potential human immunodeficiency virus type 1 (HIV-1) integrase inhibitors during virus replication in cell culture, we used a modified nested Alu-PCR assay to quantify integrated HIV DNA in combination with the quantitative analysis of extrachromosomal HIV DNA. The two diketo acid integrase inhibitors (L-708,906 and L-731,988) blocked the accumulation of integrated HIV-1 DNA in T cells following infection but did not alter levels of newly synthesized extrachromosomal HIV DNA. In contrast, we demonstrated that L17 (a member of the bisaroyl hydrazine family of integrase inhibitors) and AR177 (an oligonucleotide inhibitor) blocked the HIV replication cycle at, or prior to, reverse transcription, although both drugs inhibited integrase activity in cell-free assays. Quercetin dihydrate (a flavone) was shown to not have any antiviral activity in our system despite reported anti-integration properties in cell-free assays. This refined Alu-PCR assay for HIV provirus is a useful tool for screening anti-integration compounds identified in biochemical assays for their ability to inhibit the accumulation of integrated HIV DNA in cell culture, and it may be useful for studying the effects of these inhibitors in clinical trials.