bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Human Immunodeficiency Virus by a New Class of Pyridine Oxide Derivatives
Authors: Stevens Miguel , Pannecouque Christophe , De Clercq Erik , Balzarini Jan 
Published: August 2003

ABSTRACT

A new class of pyridine oxide derivatives as inhibitors of human immunodeficiency virus type 1 (HIV-1) and/or HIV-2 replication in cell culture has been identified. The compounds, which specifically inhibit HIV-1, behave as typical nonnucleoside reverse transcriptase inhibitors (NNRTIs). The most active congener of this group, JPL-133 (UC-B3096), has a 50% effective concentration of 0.05 μg/ml for HIV-1(III
B
) with a selectivity index of approximately 760 in CEM cell cultures. However, the cytostatic activity of most pyridine oxide derivatives highly depended on the nature of the cell line. All compounds, including those pyridine oxide derivatives that inhibit both HIV-1 and HIV-2 replication, select for NNRTI-characteristic mutations in the HIV-1 reverse transcriptase of HIV-infected cell cultures (i.e., Lys103Asn, Val108Ile, Glu138Lys, Tyr181Cys and Tyr188His). These amino acid mutations emerged mostly through transition of guanine to adenine or adenine to guanine in the corresponding codons of the reverse transcriptase (RT) gene. The HIV-1-specific pyridine oxide derivatives lost their antiviral activity against HIV-1 strains containing these mutations in the RT. However, most compounds retained pronounced antiviral potency against virus strains that contained other NNRTI-characteristic RT mutations, such as Leu100Ile and Val179Asp. Furthermore, the complete lack of inhibitory activity of the pyridine oxide derivatives against recombinant HIV-2 RT and partial retention of anti-HIV-1 activity against HIV-1 strains that contain a variety of HIV-1-characteristic mutations suggest that the pyridine oxide derivatives must have a second target of antiviral action independent from HIV-1 RT.
Effects of Ser130Gly and Asp240Lys Substitutions in Extended-Spectrum β-Lactamase CTX-M-9
Authors: Aumeran C. , Chanal C. , Labia R. , Sirot D. , Sirot J. , Bonnet R. 
Published: August 2003

ABSTRACT
In CTX-M-9 extended-spectrum β-lactamases (ESBLs), an S130G mutation induced a 40- to 650-fold increase in 50% inhibitory concentrations but decreased hydrolytic activity against cefotaxime. A D240K mutation did not modify enzymatic efficiency against ceftazidime. Residue K240 could interact with Q270 and therefore not with ceftazidime, in contrast with what was observed with certain TEM/SHV-type ESBLs.
Gentamicin Delivery to
Burkholderia cepacia
Group IIIa Strains via Membrane Vesicles from
Pseudomonas aeruginosa
PAO1
Authors: Allan Nick D. , Beveridge Terry J. 
Published: August 2003

ABSTRACT

When
Pseudomonas aeruginosa
PAO1 is treated with gentamicin, it releases membrane vesicles containing gentamicin (g-MVs) and peptidoglycan hydrolase, which makes the MVs bactericidal. We evaluate the ability of g-MVs to deliver gentamicin past the intrinsic permeability barrier of group IIIa
Burkholderia cepacia
and show that strain CEP0248 with low resistance to gentamicin is killed but the highly resistant strain C5424 is not. Immunoelectron microscopy revealed that gentamicin was delivered into both strains, suggesting that there might be another mechanism of resistance in C5424.
S
-Adenosyl-
l
-Methionine Inhibitors Δ
24
-Sterol Methyltransferase and Δ
24(28)
-Sterol Methylreductase as Possible Agents against
Paracoccidioides brasiliensis
Authors: Visbal Gonzalo , Alvarez Alvaro , Moreno Belisario , San-Blas Gioconda 
Published: August 2003

ABSTRACT

We studied the antiproliferative effects of three azasterol analogs [piperidyl-2-yl-5α-pregnan-3β,20(
R
)-diol (AZA-1), 22-piperidin-2-yl-pregnan-22(
S
),3β-diol (AZA-2), and 22-piperidin-3-yl-pregnan-22(
S
),3β-diol (AZA-3)] and their effects on the lipid composition of the pathogenic yeastlike phase of the dimorphic fungus
Paracoccidioides brasiliensis
. Inhibition was 100% for AZA-1 at 5 μM, 62% for AZA-2 at 10 μM, and 100% for AZA-3 at 0.5 μM. The analogs inhibited different stages of the sterol biosynthesis pathway.
Discordant Resistance to Kanamycin and Amikacin in Drug-Resistant
Mycobacterium tuberculosis
Authors: Krüüner Annika , Jureen Pontus , Levina Klavdia , Ghebremichael Solomon , Hoffner Sven 
Published: August 2003

ABSTRACT

It is generally thought that there is full cross-resistance in
Mycobacterium tuberculosis
between the aminoglycoside drugs kanamycin and amikacin. However, kanamycin resistance and amikacin susceptibility were seen in 43 of 79 (54%) multidrug-resistant Estonian isolates, indicating that there might be a need to test the resistance of
M. tuberculosis
isolates to both drugs.
Activity of Daptomycin against Recent North American Isolates of
Streptococcus pneumoniae
Authors: Restrepo M. I. , Velez J. A. , McElmeel M. L. , Whitney C. G. , Jorgensen J. H. 
Published: August 2003

ABSTRACT

Daptomycin MICs at which 50% of isolates were inhibited (MIC
50
s) and MIC
90
s determined by the NCCLS broth microdilution method were both 0.25 μg/ml (range, 0.06 to 2 μg/ml) for 350 pneumococcal isolates. MICs determined by E test strips on commercially prepared Mueller-Hinton sheep blood agars with different calcium contents were 2 to 3 dilutions higher than those determined by strips that contained daptomycin plus calcium. Daptomycin zone diameters varied little on the same media.
New Plasmid-Borne Antibiotic Resistance Gene Cluster in
Pasteurella multocida
Authors: Kehrenberg Corinna , Tham Nga Thi Thu , Schwarz Stefan 
Published: August 2003

ABSTRACT

A new antibiotic resistance gene cluster comprising genes for sulfonamide (
sul2
), streptomycin (
strA
-
strB
), and tetracycline [
tetR
-
tet
(H)] resistance was detected on plasmid pVM111 from
Pasteurella multocida
. The
tetR
-
tet
(H) gene region was inserted between
sul2
and
strA
, possibly by illegitimate recombination. Two potential recombination sites of 18 and 25 bp were identified.
A New TEM-Derived Extended-Spectrum β-Lactamase (TEM-91) with an R164C Substitution at the Ω-Loop Confers Ceftazidime Resistance
Authors: Kurokawa Hiroshi , Shibata Naohiro , Doi Yohei , Shibayama Keigo , Kamachi Kazunari , Yagi Tetsuya , Arakawa Yoshichika 
Published: August 2003

ABSTRACTA new plasmid-mediated TEM-derived extended-spectrum β-lactamase, TEM-91, was identified in a ceftazidime-resistant (MIC, >128 μg per ml)Escherichia colistrain isolated in 1996 in Japan. TEM-91 has three amino acid substitutions, R164C, M184T, and E240K, compared with TEM-1 penicillinase. The isoelectric point (pI),Km, andkcatof TEM-91 for ceftazidime were 5.7, 179 μM, and 29.0 s−1, respectively. TheKiof clavulanic acid for ceftazidime hydrolysis was 30.3 nM.
Effects of 16S rRNA Gene Mutations on Tetracycline Resistance in
Helicobacter pylori
Authors: Gerrits Monique M. , Berning Marco , Van Vliet Arnoud H. M. , Kuipers Ernst J. , Kusters Johannes G. 
Published: August 2003

ABSTRACT

The triple-base-pair 16S rDNA mutation AGA
926-928
→TTC mediates high-level tetracycline resistance in
Helicobacter pylori
. In contrast, single- and double-base-pair mutations mediated only low-level tetracycline resistance and decreased growth rates in the presence of tetracycline, explaining the preference for the TTC mutation in tetracycline-resistant
H. pylori
isolates.
Measurement of Cefaclor and Amoxicillin-Clavulanic Acid Levels in Middle-Ear Fluid in Patients with Acute Otitis Media
Authors: Scaglione F. , Caronzolo D. , Pintucci J. P. , Fraschini F. 
Published: August 2003

ABSTRACT
Concentrations of cefaclor (CFC) or amoxicillin-clavulanic acid (AMX/CA) in middle-ear fluid collected preserving the stability and clearing the cell contents has been compared to those obtained using the traditional method. Sixty-seven children with effusive otitis media were treated orally with CFC (20 mg/kg of body weight) or AMX/CA (20 mg/kg) (4:1 ratio). The concentrations in cell-free fluid (C−) appear higher than those in the total fluid (C+) (as assayed traditionally).
Functional Cloning and Characterization of a Multidrug Efflux Pump, MexHI-OpmD, from a
Pseudomonas aeruginosa
Mutant
Authors: Sekiya Hiroshi , Mima Takehiko , Morita Yuji , Kuroda Teruo , Mizushima Tohru , Tsuchiya Tomofusa 
Published: August 2003

ABSTRACT

We isolated mutant YM644, which showed elevated resistance to norfloxacin, ethidium bromide, acriflavine, and rhodamine 6G, from
Pseudomonas aeruginosa
YM64, a strain that lacks four major multidrug efflux pumps. The genes responsible for the resistance were
mexHI-opmD.
Elevated ethidium extrusion was observed with cells of YM644 and YM64 harboring a plasmid carrying the genes. Disruption of the genes in the chromosomal DNA of YM644 made the cells sensitive to the drugs.
Multiple Antibiotic Resistance Gene Transfer from Animal to Human Enterococci in the Digestive Tract of Gnotobiotic Mice
Authors: Moubareck C. , Bourgeois N. , Courvalin P. , Doucet-Populaire F. 
Published: August 2003

ABSTRACT

It has been proposed that food animals represent the source of glycopeptide resistance genes present in enterococci from humans. We demonstrated the transfer of
vanA
and of other resistance genes from porcine to human
Enterococcus faecium
at high frequency in the digestive tract of gnotobiotic mice. Tylosin in the drinking water favored colonization by transconjugants.
Novel
Pseudomonas aeruginosa
Gene That Suppresses Tolerance to Carbapenems
Authors: Taniguchi Kazuko , Ono Tsuneko , Murakami Keiji , Viducic Darija , Kayama Sizuo , Hirota Katsuhiko , Nemoto Ken , Miyake Yoichiro 
Published: August 2003

ABSTRACT

A biapenem-tolerant mutant of
Pseudomonas aeruginosa
was isolated by Tn
1737
KH insertion. The survival of the mutant 3 h after the addition of biapenem was about 1,000 times greater than that of the wild type. The mutant was also tolerant to other biapenems, such as imipenem, panipenem, and meropenem.
Efficacy of Linezolid Alone or in Combination with Vancomycin for Treatment of Experimental Endocarditis Due to Methicillin-Resistant
Staphylococcus aureus
Authors: Chiang Fu-Yu , Climo Michael 
Published: August 2003

ABSTRACT

The levels of effectiveness of linezolid, vancomycin, and the combination of linezolid and vancomycin were compared in the rabbit model of endocarditis caused by a clinical methicillin-resistant
Staphylococcus aureus
(MRSA) isolate. Vancomycin alone was more effective than either linezolid alone or the combination of linezolid and vancomycin for the treatment of endocarditis due to MRSA.
Chemotherapeutic Potential of Orally Administered Poly(Lactide-Co-Glycolide) Microparticles Containing Isoniazid, Rifampin, and Pyrazinamide against Experimental Tuberculosis
Authors: ul-Ain Qurrat , Sharma Sadhna , Khuller G. K. 
Published: August 2003

ABSTRACT
Poly(lactide-co-glycolide) (PLG) microspheres (diameter, less than 3 μm) containing isoniazid, rifampin, and pyrazinamide were used in a sustained oral drug delivery system to treat murine tuberculosis. Drug levels above the MIC were observed up to 72 h in plasma and for 9 days in various organs. Relative bioavailability of encapsulated drugs was greater than that of free drugs. Chemotherapy results showed better or equivalent clearance of bacilli in the PLG-drug-administered group (weekly) than with free drugs (daily).
In Vitro Activities of ABT-492, a New Fluoroquinolone, against 155 Aerobic and 171 Anaerobic Pathogens Isolated from Antral Sinus Puncture Specimens from Patients with Sinusitis
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi A. , Tyrrell Kerin L. , Fernandez Helen T. 
Published: August 2003

ABSTRACT

ABT-492 exhibited excellent in vitro activities against all 326 aerobic and anaerobic antral puncture sinus isolates tested with MICs (in micrograms per milliliter) at which 90% of the isolates tested were inhibited as follows:
Haemophilus influenzae
, 0.001;
Moraxella catarrhalis
, 0.008; and
Streptococcus pneumoniae
, 0.015. It was four- to sixfold more active than other fluoroquinolones, including against levofloxacin-resistant strains of
S. pneumoniae
, methicillin-resistant
Staphylococcus aureus
, and
Prevotella
species.
Postantibiotic Effects of Daptomycin against 14 Staphylococcal and Pneumococcal Clinical Isolates
Authors: Pankuch G. A. , Jacobs M. R. , Appelbaum P. C. 
Published: August 2003

ABSTRACT
Daptomycin mean staphylococcal postantibiotic effects (PAEs) were 1.1 to 6.2 h, with a mean of 2.5 h. The mean pneumococcal PAEs were 1.7 h, ranging between 1.0 and 2.5 h. The staphylococcal and pneumococcal postantibiotic sub-MIC effects at 0.4 times the MIC ranged from 3.0 to >12.0 h and 1.9 to >12.0 h, respectively.
Antitrypanosomal Activities of Fluoroquinolones with Pyrrolidinyl Substitutions
Authors: Nenortas Elizabeth , Kulikowicz Tomasz , Burri Christian , Shapiro Theresa A. 
Published: August 2003

ABSTRACT

Fluoroquinolones with pyrrolidinyl substitutions were tested against
Trypanosoma brucei
and mammalian cells. Bulky substituents at C-7 or a 1-2-bridging thiazolidine ring increased antitrypanosomal activity and selective toxicity. These compounds trap protein-DNA complexes and inhibit nucleic acid biosynthesis in trypanosomes, characteristics of topoisomerase II inhibition.
Disk Diffusion-Based Methods for Determining
Candida parapsilosis
Susceptibility to Anidulafungin
Authors: Odabasi Zekaver , Paetznick Victor , Goldstein Beth P. , Rex John H. , Ostrosky-Zeichner Luis 
Published: August 2003

ABSTRACT

Zone diameters for anidulafungin by disk diffusion for 139 isolates of
C. parapsilosis
were compared with MICs by NCCLS M27-A2 broth microdilution. The comparison was poor unless the disks were prepared by dissolving anidulafungin in 1% dimethyl sulfoxide plus 0.1% Tween 80 and testing on Mueller-Hinton agar flooded with glucose and methylene blue.
Real-Time PCR as a Versatile Tool for Investigating the Susceptibility of Human Herpesvirus 6 to Antiviral Agents
Authors: Macé Muriel , Manichanh Chaysavanh , Bonnafous Pascale , Précigout Stéphanie , Boutolleau David , Gautheret-Dejean Agnès , Agut Henri 
Published: August 2003

ABSTRACT
A quantitative real-time PCR assay was developed for the determination of antiviral drug susceptibility and growth kinetics of human herpesvirus 6. The susceptibility and fitness of a sensitive strain, HST, and its ganciclovir-resistant derivative, GCVR1, were then characterized, leading us to conclude that the mutations of this latter virus did not alter its fitness significantly.
In Vitro Activities of a New Lipopeptide, HMR 1043, against Susceptible and Resistant Gram-Positive Isolates
Authors: Bemer Pascale , Juvin Marie-Emmanuelle , Bryskier Andre , Drugeon Henri 
Published: August 2003

ABSTRACT
The purpose of this study was to compare the activity of HMR 1043 with those of daptomycin and teicoplanin against gram-positive isolates. Susceptibility tests were performed for 52 strains, 26 parental strains, including staphylococcal, streptococcal, enterococcal, and listerial strains, and 26 HMR 1043-resistant mutants obtained from parental strains by using the Szybalski method. Agar dilution and disk diffusion susceptibility tests were performed by the procedures outlined by the NCCLS. HMR 1043 demonstrated good activity against susceptible and resistant gram-positive bacteria. The activity of HMR 1043 in vitro was less influenced by the presence of calcium ions than that of daptomycin. Susceptibility test breakpoints were not defined because of the poor correlation coefficients obtained with the different disks tested.
Roles of TolC-Dependent Multidrug Transporters of
Escherichia coli
in Resistance to β-Lactams
Authors: Nishino Kunihiko , Yamada Junko , Hirakawa Hidetada , Hirata Takahiro , Yamaguchi Akihito 
Published: August 2003

ABSTRACT

AcrAB exports some β-lactam antibiotics in the periplasm out of cells via an outer-membrane channel, TolC. It has been reported that eight drug transporters in
Escherichia coli
cooperate with TolC. In this study, the roles of the drug exporters of
E. coli
in β-lactam resistance were examined. We found that five of five resistance-nodulation-cell division-type drug exporters confer β-lactam antibiotic resistance, while no other drug exporters confer any β-lactam resistance even when they cooperate with TolC.
MtuA, a Lipoprotein Receptor Antigen from
Streptococcus uberis
, Is Responsible for Acquisition of Manganese during Growth in Milk and Is Essential for Infection of the Lactating Bovine Mammary Gland
Authors: Smith Amanda J. , Ward Philip N. , Field Terence R. , Jones Catherine L. , Lincoln Ruth A. , Leigh James A. 
Published: August 2003

ABSTRACT

A mutant strain of
Streptococcus uberis
(AJS001) that was unable to grow in bovine milk was isolated following random insertional mutagenesis. The level of growth in milk was restored to that of the parental strain (strain 0140J) following addition of MnSO
4
but not following addition of other metal ions. The mutant contained a single insertion within
mtuA
, a homologue of
mtsA
and
psaA
, which encode metal-binding proteins in
Streptococcus pyogenes
and
Streptococcus pneumoniae
, respectively. Strain AJS001 was unable to infect any of eight quarters on four dairy cows following intramammary challenge with 10
5
CFU. Bacteria were never recovered directly from milk of these animals but were detected following enrichment in Todd-Hewitt broth in three of eight milk samples obtained within 24 h of challenge. The animals showed no inflammatory response and no signs of mastitis. Three mammary quarters on two different animals simultaneously challenged with 600 CFU of the parental strain, strain 0140J, became colonized, shed high numbers of
S. uberis
organisms in milk, displayed a marked inflammatory response to infection, and showed overt signs of mastitis. These data indicate that
mtuA
was required for efficient uptake of Mn
2+
during growth in bovine milk and infection of the lactating bovine mammary gland.
Role of Toll-Like Receptor 4 in Macrophage Activation and Tolerance duringSalmonella entericaSerovar Typhimurium Infection
Authors: Li Qian , Cherayil Bobby J. 
Published: August 2003

ABSTRACTToll-like receptors (TLRs) play an important role in the innate immune response, particularly in the initial interaction between the infecting microorganism and phagocytic cells, such as macrophages. We investigated the role of TLR4 during infection of primary murine peritoneal macrophages withSalmonella entericaserovar Typhimurium. We found that macrophages from the C3H/HeJ mouse strain, which carries a functionally inactive Tlr4 gene, exhibit marked impairment of tumor necrosis factor alpha (TNF-α) secretion in response toS. entericaserovar Typhimurium infection. However, activation of extracellular growth factor-regulated kinase and NF-κB signaling pathways was relatively unaffected, as was increased expression of TNF-α mRNA. Furthermore, macrophage tolerance, which is associated with increased expression of the NF-κB p50 and p52 subunits, was induced byS. entericaserovar Typhimurium even in the absence of functional TLR4. These results indicate that during infection of macrophages byS. entericaserovar Typhimurium, TLR4 signals are required at a posttranscriptional step to maximize secretion of TNF-α. Signals delivered by pattern recognition receptors other than TLR4 are sufficient for the increased expression of the TNF-α transcript and at least some genes associated with macrophage tolerance.
Interactions of
Campylobacter jejuni
Cytolethal Distending Toxin Subunits CdtA and CdtC with HeLa Cells
Authors: Lee Robert B. , Hassane Duane C. , Cottle Daniel L. , Pickett Carol L. 
Published: August 2003

ABSTRACT

Campylobacter jejuni
produces a toxin, called cytolethal distending toxin (CDT), which causes direct DNA damage leading to invocation of DNA damage checkpoint pathways. The affected cells arrest in G
1
or G
2
and eventually die. CDT consists of three protein subunits, CdtA, CdtB, and CdtC, with CdtB recently identified as a nuclease. However, little is known about the functions of CdtA or CdtC. In this work, enzyme-linked immunosorbent assay-based experiments were used to show, for the first time, that both CdtA and CdtC bound with specificity to the surface of HeLa cells, whereas CdtB did not. Varying the order of the addition of subunits for reconstitution of the holotoxin had no effect on activity. In addition, mutants containing deletions of conserved regions of CdtA and CdtC were able to bind to the surface of HeLa cells but were not able to participate in holotoxin assembly. Finally, both Cdt mutant subunits were able to effectively compete with CDT holotoxin in the HeLa cell binding assay.
Increased Mortality and Dysregulated Cytokine Production in Tumor Necrosis Factor Receptor 1-Deficient Mice following SystemicKlebsiella pneumoniaeInfection
Authors: Moore Thomas A. , Perry Michelle L. , Getsoian Andrew G. , Monteleon Christine L. , Cogen Anna L. , Standiford Theodore J. 
Published: August 2003

ABSTRACTA significant clinical complication of pulmonary infections withKlebsiella pneumoniaeis peripheral blood dissemination, resulting in a systemic infection concurrent with the localized pulmonary infection. In this context, little is known about the role of tumor necrosis factor receptor 1 (TNFR1)-mediated innate immune responses during systemicKlebsiellainfections. Mice lacking TNFR1 were significantly more susceptible toKlebsiella-induced mortality following intravenous inoculation. Bacterial clearance was impaired in TNFR1-deficient mice at early times following infection. Unexpectedly, bacterial burdens at the onset of mortality (days 2 to 3 postinfection) were not higher in mice lacking TNFR1. However, elevated production of liver-associated proinflammatory cytokines (interleukin-12, tumor necrosis factor alpha [TNF-α[, and gamma interferon [IFN-γ]) and chemokines (MIP-1α, MIP-2, and MCP-1) was observed within the first 24 h of infection. Additionally, excessive plasma-associated IFN-γ was also observed late in the course of infection (day 3). Spleen cells from day-3 infected TNFR1-deficient mice secreted markedly enhanced levels of IFN-γ when cultured in vitro. Additionally, there was a marked increase in the total number of activated lymphocyte subsets as indicated by CD69 upregulation. A notable exception was the sharp decrease in the frequency of splenic NK T cells in infected TNFR1 knockout (KO) mice. Anti-TNF-α therapy in TNFR1 KO mice significantly reduced chemokine production and liver injury. Combined, these data indicate a dysregulated antibacterial host response following intravenousKlebsiellainfection in the absence of TNFR1 signaling, resulting in heightened cytokine production and hyperactivation of specific splenic lymphocyte subsets.