bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Azole Antifungal Drugs on the Transition from Yeast Cells to Hyphae in Susceptible and Resistant Isolates of the Pathogenic Yeast
Candida albicans
Authors: Ha Kien C. , White Theodore C. 
Published: October 2018

ABSTRACT

Oral infections caused by the yeast
Candida albicans
are some of the most frequent and earliest opportunistic infections in human immunodeficiency virus-infected patients. The widespread use of azole antifungal drugs has led to the development of drug resistance, creating a major problem in the treatment of yeast infections in AIDS patients and other immunocompromised individuals. Several molecular mechanisms that contribute to drug resistance have been identified. In
C. albicans
, the ability to morphologically switch from yeast cells (blastospores) to filamentous forms (hyphae) is an important virulence factor which contributes to the dissemination of
Candida
in host tissues and which promotes infection and invasion. A positive correlation between the level of antifungal drug resistance and the ability to form hyphae in the presence of azole drugs has been identified. Under hypha-inducing conditions in the presence of an azole drug, resistant clinical isolates form hyphae, while susceptible yeast isolates do not. This correlation is observed in a random sample from a population of susceptible and resistant isolates and is independent of the mechanisms of resistance.
35
S-methionine incorporation suggests that growth inhibition is not sufficient to explain the inhibition of hyphal formation, but it may contribute to this inhibition.
Impact ofgyrAandparCMutations on Quinolone Resistance, Doubling Time, and Supercoiling Degree ofEscherichia coli
Authors: Bagel Simone , Hüllen Volker , Wiedemann Bernd , Heisig Peter 
Published: October 2018

ABSTRACTIsogenic mutants derived from quinolone-susceptible isolate WT by introducinggyrA(S83L, D87G) andparC(S80I, E84K) mutations associated with quinolone resistance were characterized with respect to quinolone resistance, growth rate, and degree of global supercoiling. The latter was determined by use of a pair of reporter plasmids carrying supercoiling-dependent promoters pgyrAand ptopA, respectively, transcriptionally fused to the reporter geneblacoding for TEM-1 β-lactamase. The quotient (Qsc) of the β-lactamase specific activity determined for a mutant carrying either plasmid was taken as a measure of the degree of global supercoiling. These Qsc data were comparable to results obtained from the separation of topoisomers of plasmid pBR322 on chloroquine-containing agarose gels and indicate a reduced degree of negative supercoiling in resistant mutants relative to the parent, WT. The S83L mutation ingyrAhad the strongest influence on quinolone resistance while leaving other parameters nearly unaffected. ThegyrAdouble mutation (S83L plus D87G) had an effect on quinolone resistance similar to that of a single mutation. Phenotypic expression of theparCmutation (S80I) was dependent on the presence of at least onegyrAmutation. Expression of high-level fluoroquinolone resistance (ciprofloxacin MIC, >4 μg/ml) required a combination of thegyrAdouble mutation and oneparCmutation (S80I or E84K). Such mutants showed considerable alterations of growth rate, global supercoiling, or both. Introduction of aparCmutation affected neither the doubling time nor the degree of supercoiling, while the presence of thegyrAD87G mutation was associated with a significant reduction in the degree of DNA supercoiling.
Lipopolyamines: Novel Antiendotoxin Compounds That Reduce Mortality in Experimental Sepsis Caused by Gram-Negative Bacteria
Authors: David Sunil A. , Silverstein Richard , Amura Claudia R. , Kielian Tammy , Morrison David C. 
Published: October 2018

ABSTRACTThe interactions of lipopolyamines, a class of structurally unique compounds currently being used as transfection (lipofection) agents, with lipopolysaccharide (LPS) have been characterized. Our studies have demonstrated that 1,3-di-oleoyloxy-2-(6-carboxyspermyl)-propylamide), available commercially as DOSPER, binds to purified LPS with an affinity of about 1/10 that of polymyxin B. This essentially nontoxic compound inhibits, in a dose-dependent manner, LPS-induced activation of theLimulusclotting cascade and the production of tumor necrosis factor alpha (TNF-α) interleukin-6 (IL-6), and nitric oxide from LPS-stimulated J774.A1 cells, a murine macrophage-like cell line. Cytokine inhibition is paralleled by decreased steady-state levels of TNF-α and IL-6 mRNA and inhibits the nuclear translocation of nuclear factor kappa B. These findings suggest that the lipopolyamine compound sequesters LPS, thereby blocking downstream cellular activation events that lead to the production of proinflammatory mediators. Administration of DOSPER tod-galactosamine-sensitized mice challenged either with LPS or withEscherichia coliorganisms provided significant protection against lethality both with and without antibiotic chemotherapy. Partial protection is evident in LPS-challenged mice treated with DOSPER as late as 2 to 4 h following the endotoxin challenge. A greater degree of protection is observed inE. coli-challenged animals receiving ceftazidime than in those receiving imipenem, which is probably attributable to the higher levels of LPS released in vivo by the former antibiotic. Potent antiendotoxic activity, low toxicity, and ease of synthesis render the lipopolyamines candidate endotoxin-sequestering agents of potential significant therapeutic value.
A New Resistance Gene,
linB
, Conferring Resistance to Lincosamides by Nucleotidylation in
Enterococcus faecium
HM1025
Authors: Bozdogan Bülent , Berrezouga Latifa , Kuo Ming-Shang , Yurek David A. , Farley Kathleen A. , Stockman Brian J. , Leclercq Roland 
Published: October 2018

ABSTRACT

Resistance to lincomycin and clindamycin in the clinical isolate
Enterococcus faecium
HM1025 is due to a ribosomal methylase encoded by an
ermAM
-like gene and the plasmid-mediated inactivation of these antibiotics. We have cloned and determined the nucleotide sequence of the gene responsible for the inactivation of lincosamides,
linB
. This gene encodes a 267-amino-acid lincosamide nucleotidyltransferase. The enzyme catalyzes 3-(5′-adenylation) (the adenylation of the hydroxyl group in position 3 of the molecules) of lincomycin and clindamycin. Expression of
linB
was observed in both
Escherichia coli
and
Staphylococcus aureus
. The deduced amino acid sequence of the enzyme did not display any significant homology with staphylococcal nucleotidyltransferases encoded by
linA
and
linA
′ genes. Sequences homologous to
linB
were found in 14 other clinical isolates of
E. faecium
, indicating the spread of the resistance trait in this species.
In Vivo and In Vitro Toxicodynamic Analyses of New Quinolone-and Nonsteroidal Anti-Inflammatory Drug-Induced Effects on the Central Nervous System
Authors: Kita Hideki , Matsuo Hirotami , Takanaga Hitomi , Kawakami Junichi , Yamamoto Koujirou , Iga Tatsuji , Naito Mikihiko , Tsuruo Takashi , Asanuma Atsushi , Yanagisawa Keiji , Sawada Yasufumi 
Published: October 2018

ABSTRACT

We investigated the correlation between an in vivo isobologram based on the concentrations of new quinolones (NQs) in brain tissue and the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for the occurrence of convulsions in mice and an in vitro isobologram based on the concentrations of both drugs for changes in the γ-aminobutyric acid (GABA)-induced current response in
Xenopus
oocytes injected with mRNA from mouse brains in the presence of NQs and/or NSAIDs. After the administration of enoxacin (ENX) in the presence or absence of felbinac (FLB), ketoprofen (KTP), or flurbiprofen (FRP), a synergistic effect was observed in the isobologram based on the threshold concentration in brain tissue between mice with convulsions and those without convulsions. The three NSAIDs did not affect the pharmacokinetic behavior of ENX in the brain. However, the ENX-induced inhibition of the GABA response in the GABA
A
receptor expressed in
Xenopus
oocytes was enhanced in the presence of the three NSAIDs. The inhibition ratio profiles of the GABA responses for both drugs were analyzed with a newly developed toxicodynamic model. The inhibitory profiles for ENX in the presence of NSAIDs followed the order KTP (1.2 μM) > FRP (0.3 μM) > FLB (0.2 μM). These were 50- to 280-fold smaller than those observed in the absence of NSAIDs. The inhibition ratio (0.01 to 0.02) of the GABA
A
receptor in the presence of both drugs was well-fitted to the isobologram based on threshold concentrations of both drugs in brain tissue between mice with convulsions and those without convulsions, despite the presence of NSAIDs. In mice with convulsions, the inhibitory profiles of the threshold concentrations of both drugs in brain tissue of mice with convulsions and those without convulsions can be predicted quantitatively by using in vitro GABA response data and toxicodynamic model.
Integron- and Carbenicillinase-Mediated Reduced Susceptibility to Amoxicillin-Clavulanic Acid in Isolates of Multidrug-Resistant
Salmonella enterica
Serotype Typhimurium DT104 from French Patients
Authors: Poirel Laurent , Guibert Michele , Bellais Samuel , Naas Thierry , Nordmann Patrice 
Published: October 2018

ABSTRACT

Fifty-seven
Salmonella enterica
serotype Typhimurium (
S. typhimurium
) isolates were collected from human patients in two French hospitals, Hôpital Antoine Béclère (Clamart, France) and Hôpital Bicêtre (Le Kremlin-Bicêtre, France), between 1996 and 1997. Thirty of them (52 percent) were resistant to amino-, carbeni-, and ureidopenicillins, had reduced susceptibility to amoxicillin-clavulanic acid, were susceptible to cephalothin, and were resistant to sulfonamides, streptomycin, chloramphenicol, and tetracyclines. All these strains possessed a
bla
PSE-1
-like gene and were of phage type DT104. Ten of them were studied in more detail, which revealed that
bla
PSE-1
is located on the variable region of a class 1 integron. This integron was found to be chromosomally located, as was another class 1 integron containing
aadA2
, a streptomycin-spectinomycin resistance gene. The reduced susceptibility to amoxicillin-clavulanic acid (and to ticarcillin-clavulanic acid) may result from the high level of hydrolysis of the β-lactam rather than to the clavulanic acid resistance properties of PSE-1 in these clonally related
S. typhimurium
isolates.
Carbapenem Resistance in
Escherichia coli
Associated with Plasmid-Determined CMY-4 β-Lactamase Production and Loss of an Outer Membrane Protein
Authors: Stapleton Paul D. , Shannon Kevin P. , French Gary L. 
Published: October 2018

ABSTRACT

Three cefoxitin-resistant
Escherichia coli
isolates from stool specimens of a patient with leukemia were either resistant, intermediate, or sensitive to imipenem. Conjugation experiments showed that cefoxitin resistance, but not imipenem resistance, was transferable. All isolates were shown by isoelectric focusing to produce two β-lactamases with isoelectric points of 5.4 (TEM-1, confirmed by sequencing of a PCR product) and >8.5 (consistent with a class C β-lactamase). The gene coding for the unknown β-lactamase was cloned and sequenced and revealed an enzyme which had 99.9% sequence identity with the plasmid-determined class C β-lactamase CMY-2. The cloned β-lactamase gene differed from
bla
CMY-2
at one nucleotide position that resulted in an amino acid change, tryptophan to arginine at position 221. We propose that this enzyme be designated CMY-4. Both the imipenem-resistant and -intermediate isolates lacked a 38-kDa outer membrane protein (OMP) that was present in the imipenem-sensitive isolate. The lack of an OMP alone did not explain the difference in carbapenem susceptibilities observed. However, measurement of β-lactamase activities (including measurements under conditions where TEM-1 β-lactamase was inhibited) indicated that the imipenem-intermediate isolate expressed six- to eightfold less β-lactamase than did the other isolates. This study illustrates that carbapenem resistance in
E. coli
can arise from high-level expression of plasmid-mediated class C β-lactamase combined with an OMP deficiency. Furthermore, in the presence of an OMP deficiency, the level of expression of a plasmid-mediated class C β-lactamase is an important factor in determining whether
E. coli
isolates are fully resistant to carbapenems.
Pharmacokinetics of Ampicillin and Sulbactam in Pediatric Patients
Authors: Nahata Milap C. , Vashi Vijay I. , Swanson Robert N. , Messig Michael A. , Chung Menger 
Published: October 2018

ABSTRACT
Intravenous ampicillin-sulbactam is effective in the treatment of various infections in adults, but little is known about the pharmacokinetics (PK) of ampicillin-sulbactam in children. The objective of this study was to determine the PK of ampicillin and sulbactam in pediatric patients with intra-abdominal infection, skin and/or skin structure infection, or periorbital-preseptal and facial cellulitis. Intravenous ampicillin and sulbactam (2:1), 40 to 80 mg/kg of body weight, were given every 6 h for 2 to 6 days to 28 pediatric patients. The ages ranged from 1 to 6 years for 10 patients, 6.1 to 10 years for 9 patients, and 10.1 to 12 years for 9 patients. Multiple blood samples were obtained and analyzed for ampicillin and sulbactam in plasma and serum by high-performance liquid chromatography. The mean maximum concentration of drug in serum ranged from 177 to 200 μg/ml for ampicillin and 82 to 102 μg/ml for sulbactam in the three age groups. The mean total clearance, steady-state distribution volume, and half-life were 4.76 ml/min/kg, 0.32 liter/kg, and 0.77 h, respectively, for ampicillin and 4.95 ml/min/kg, 0.34 liter/kg, and 0.81 h, respectively, for sulbactam. Dose or gender did not affect the PK of ampicillin or sulbactam. The PK of ampicillin and sulbactam in these patients were comparable to those reported in adults. The combination was well tolerated in pediatric patients.
Selective Effect of 2′,6′-Dihydroxy-4′-Methoxychalcone Isolated fromPiper aduncumonLeishmania amazonensis
Authors: Torres-Santos Eduardo Caio , Moreira Davyson Lima , Kaplan Maria Auxiliadora C. , Meirelles Maria Nazareth , Rossi-Bergmann Bartira 
Published: October 2018

ABSTRACT2′,6′-Dihydroxy-4′-methoxychalcone (DMC) was purified from the dichloromethane extract ofPiper aduncuminflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes ofLeishmania amazonensis, with 50% effective doses of 0.5 and 24 μg/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 μg/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 μg of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.
In Vitro and In Vivo Experimental Activities of Antifungal Agents against
Fusarium solani
Authors: Guarro J. , Pujol I. , Mayayo E. 
Published: October 2018

ABSTRACT

In the treatment of disseminated
Fusarium
infections, amphotericin B either alone or in combination with flucytosine and rifampin is the drug therapy most frequently used. The efficacy of these antifungal drugs was evaluated in a murine disseminated-infection model, with five strains of
Fusarium solani
. All the treatments were clearly ineffective.
Genetic Characterization of Resistance to Extended-Spectrum β-Lactams in
Klebsiella oxytoca
Isolates Recovered from Patients with Septicemia at Hospitals in the Stockholm Area
Authors: Wu Shang Wei , Dornbusch Kathrine , Kronvall Göran 
Published: October 2018

ABSTRACT

Two β-lactamase gene regions were characterized by DNA sequencing in eight clinical isolates of
Klebsiella oxytoca
. The
bla
OXY-2a
region encoded a β-lactamase nearly identical to OXY-2 (one amino acid residue substituted) and conferred aztreonam and cefuroxime resistance on the
K. oxytoca
isolates. Overproduction of OXY-2a was caused by a G-to-A substitution of the fifth nucleotide in the −10 consensus sequence of
bla
OXY-2a
. The
bla
OXY-1a
was identified in a susceptible strain, and the OXY-1a enzyme differed from OXY-1 by two amino acid residues.
Characterization and Nucleotide Sequence of a
Klebsiella oxytoca
Cryptic Plasmid Encoding a CMY-Type β-Lactamase: Confirmation that the Plasmid-Mediated Cephamycinase Originated from the
Citrobacter freundii
AmpC β-Lactamase
Authors: Wu Shang Wei , Dornbusch Kathrine , Kronvall Göran , Norgren Mari 
Published: October 2018

ABSTRACT

Plasmid pTKH11, originally obtained by electroporation of a
Klebsiella oxytoca
plasmid preparation into
Escherichia coli
XAC, expressed a high level of an AmpC-like β-lactamase. The enzyme, designated CMY-5, conferred resistance to extended-spectrum β-lactams in
E. coli
; nevertheless, the phenotype was cryptic in the
K. oxytoca
donor. Determination of the complete nucleotide sequence of pTKH11 revealed that the 8,193-bp plasmid encoded seven open reading frames, including that for the CMY-5 β-lactamase (
bla
CMY-5
). The
bla
CMY-5
product was similar to the plasmidic CMY-2 β-lactamase of
K. pneumoniae
and the chromosomal AmpC of
Citrobacter freundii
, with 99.7 and 97.0% identities, respectively; there was a substitution of phenylalanine in CMY-5 for isoleucine 105 in CMY-2.
bla
CMY-5
was followed by the
Blc
and
SugE
genes of
C. freundii
, and this cluster exhibited a genetic organization identical to that of the
ampC
region on the chromosome of
C. freundii
; these results confirmed that
C. freundii
AmpC was the evolutionary origin of the plasmidic cephamycinases. In the
K. oxytoca
host, the copy number of pTKH11 was very low and the plasmid coexisted with plasmid pNBL63. Analysis of the replication regions of the two plasmids revealed 97% sequence similarity in the RNA I transcripts; this result implied that the two plasmids might be incompatible. Incompatibility of the two plasmids might explain the cryptic phenotype of
bla
CMY-5
in
K. oxytoca
through an exclusion effect on pTKH11 by resident plasmid pNBL63.
Serine Protease Inhibitors Block Invasion of Host Cells by
Toxoplasma gondii
Authors: Conseil V. , Soête M. , Dubremetz J. F. 
Published: October 2018

ABSTRACT

We investigated the effect of protease inhibitors on the asexual development of the protozoan parasite
Toxoplasma gondii
. Among the inhibitors tested only two irreversible serine protease inhibitors, 3,4-dichloroisocoumarin and 4-(2-aminoethyl)-benzenesulfonyl fluoride, clearly prevented invasion of the host cells by specifically affecting parasite targets in a dose-dependent manner, with 50% inhibitory concentrations between 1 and 5 and 50 and 100 μM, respectively. Neither compound significantly affected parasite morphology, basic metabolism, or gliding motility within the range of the experimental conditions in which inhibition of invasion was demonstrated. No partial invasion was observed, meaning that inhibition occurred at an early stage of the interaction. These results suggest that at least one serine protease of the parasite is involved in the invasive process of
T. gondii
.
Emergence of Antibiotic-Resistant
Pseudomonas aeruginosa
: Comparison of Risks Associated with Different Antipseudomonal Agents
Authors: Carmeli Yehuda , Troillet Nicolas , Eliopoulos George M. , Samore Matthew H. 
Published: October 2018

ABSTRACT

Pseudomonas aeruginosa
is a leading cause of nosocomial infections. The risk of emergence of antibiotic resistance may vary with different antibiotic treatments. To compare the risks of emergence of resistance associated with four antipseudomonal agents, ciprofloxacin, ceftazidime, imipenem, and piperacillin, we conducted a cohort study, assessing relative risks for emergence of resistant
P. aeruginosa
in patients treated with any of these drugs. A total of 271 patients (followed for 3,810 days) with infections due to
P. aeruginosa
were treated with the study agents. Resistance emerged in 28 patients (10.2%). Adjusted hazard ratios for the emergence of resistance were as follows: ceftazidime, 0.7 (
P
= 0.4); ciprofloxacin, 0.8 (
P
= 0.6); imipenem, 2.8 (
P
= 0.02); and piperacillin, 1.7 (
P
= 0.3). Hazard ratios for emergence of resistance to each individual agent associated with treatment with the same agent were as follows: ceftazidime, 0.8 (
P
= 0.7); ciprofloxacin, 9.2 (
P
= 0.04); imipenem, 44 (
P
= 0.001); and piperacillin, 5.2 (
P
= 0.01). We concluded that there were evident differences among antibiotics in the likelihood that their use would allow emergence of resistance in
P. aeruginosa
. Ceftazidime was associated with the lowest risk, and imipenem had the highest risk.
Randomized, Placebo-Controlled, Double-Blind Trial To Evaluate the Efficacy of Mupirocin for Eradicating Carriage of Methicillin-Resistant
Staphylococcus aureus
Authors: Harbarth Stephan , Dharan Sasi , Liassine Nadia , Herrault Pascale , Auckenthaler Raymond , Pittet Didier 
Published: October 2018

ABSTRACT

Mupirocin has been widely used for the clearance of nasal methicillin-resistant
Staphylococcus aureus
(MRSA) carriage during outbreaks, but no placebo-controlled trial has evaluated its value for eradicating MRSA carriage at multiple body sites in settings where MRSA is not epidemic. In a 1,500-bed teaching hospital with endemic MRSA, 102 patients colonized with MRSA were randomized into a double-blind, placebo-controlled trial and treated with either mupirocin (group M) or placebo (group P) applied to the anterior nares for 5 days; both groups used chlorhexidine soap for body washing. Follow-up screening, susceptibility testing, and genotyping were performed to evaluate treatment success, mupirocin or chlorhexidine resistance, and exogenous recolonization. At baseline, MRSA carriage was 60% in the nares, 38% in the groin, and 62% in other sites (skin lesions, urine). The MRSA eradication rate (all body sites) was 25% in group M (12 of 48 patients), compared to 18% in group P (9 of 50 patients; relative risk [RR], 0.72; 95% confidence interval [CI
95
], 0.33 to 1.55). At the end of follow-up, 44% of patients (19 of 43) were free of nasal MRSA in group M, compared to 23% (11 of 44) in group P (RR, 0.57; CI
95
, 0.31 to 1.04). Ten patients developed MRSA infections (three in group M and seven in group P). One mupirocin treatment failure was due to exogenous MRSA recolonization. No MRSA isolate showed chlorhexidine resistance or high-level mupirocin resistance; however, we observed an association (
P
= 0.003) between low-level mupirocin resistance at study entry (prevalence, 23%) and subsequent treatment failure in both study arms. These results suggest that nasal mupirocin is only marginally effective in the eradication of multisite MRSA carriage in a setting where MRSA is endemic.