bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetracycline-Resistant ClinicalHelicobacter pyloriIsolates with and without Mutations in 16S rRNA-Encoding Genes
Authors: Wu Jeng Yih , Kim Jae J. , Reddy Rita , Wang W. M. , Graham David Y. , Kwon Dong H. 
Published: January 2005

ABSTRACTTetracycline-resistantHelicobacter pyloristrains have been increasingly reported worldwide. However, only a small number of tetracycline-resistant strains have been studied with regard to possible mechanisms of resistance and those studies have focused on mutations in the tetracycline binding sites of 16S rRNA-encoding genes. We here report studies of 41 tetracycline-resistantH. pyloristrains (tetracycline MICs, 4 to 32 μg/ml) from North America (n= 12) and from East Asia (n= 29). DNA sequence analyses of 16S rRNA-encoding genes revealed that 22 (54%) of the resistant isolates carried one of five different single-nucleotide substitutions (CGA, GGA, TGA, AGC, or AGT) at the putative tetracycline binding site (AGA965-967). Single-nucleotide substitutions were associated with reduced ribosomal binding and with slightly increased tetracycline MICs (1 to 2 μg/ml). The 19 tetracycline-resistant isolates with no detectable mutations in the tetracycline binding site had normal tetracycline-ribosome binding. All tetracycline-resistant isolates, including those with and those without mutations in the tetracycline binding site, showed decreased accumulation of tetracycline. These results suggest that tetracycline resistance is multifactorial, involving alterations both in ribosomal binding and in membrane permeability.
Antiviral Treatment with Alpha Interferon Up-Regulates CD14 on Liver Macrophages and Its Soluble Form in Patients with Chronic Hepatitis B
Authors: Carotenuto Patrizia , van Riel Debby , Artsen André , Bruijns Sven , Uytdehaag Fons G. , Laman Jon D. , van Nunen Andeltje B. , Zondervan Pieter E. , De Man Robert A. , Osterhaus Albert D. , Pontesilli Oscar 
Published: January 2005

ABSTRACTTo investigate whether therapy with alpha interferon (IFN-α) induces changes in intrahepatic antigen-presenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN-α from chronic hepatitis B patients whose viral load had already been reduced by at least 8 weeks of treatment with lamivudine. HLA-DR, CD1a, and CD83 were not modified by the therapy. The intralobular expression of CD68 on Kupffer cells remained stable, denoting no changes in the number of resident macrophages during IFN-α treatment. In contrast, CD14 was weakly expressed in the absence of IFN-α and was significantly up-regulated during therapy. At the same time, the levels of soluble CD14 and interleukin-10 in plasma increased significantly. In vitro, monocytes maintained in the presence of IFN-α differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-α, T-cell infiltration in the portal spaces was reduced, mainly due to a significant decrease in the number of CD8+T cells. These findings show that IFN-α is biologically active on APCs in vivo and in vitro and suggest that this newly described regulatory function, together with the already known inhibitory effects on lymphocytes, may cooperate to reduce inflammation and consequent tissue damage in patients with chronic viral hepatitis.
Structure-Activity Relationships of Different β-Lactam Antibiotics against a Soluble Form of
Enterococcus faecium
PBP5, a Type II Bacterial Transpeptidase
Authors: Hujer Andrea M. , Kania Malgosia , Gerken Thomas , Anderson Vernon E. , Buynak John D. , Ge Xiaoxia , Caspers Patrick , Page Malcolm G. P. , Rice Louis B. , Bonomo Robert A. 
Published: January 2005

ABSTRACT

Penicillin-binding proteins (PBPs) catalyze the essential reactions in the biosynthesis of cell wall peptidoglycan from glycopeptide precursors. β-Lactam antibiotics normally interfere with this process by reacting covalently with the active site serine to form a stable acyl-enzyme. The design of novel β-lactams active against penicillin-susceptible and penicillin-resistant organisms will require a better understanding of the molecular details of this reaction. To that end, we compared the affinities of different β-lactam antibiotics to a modified soluble form of a resistant
Enterococcus faecium
PBP5 (Δ1-36 rPBP5). The soluble protein, Δ1-36 rPBP5, was expressed in
Escherichia coli
and purified, and the NH
2
-terminal protein sequence was verified by amino acid sequencing. Using β-lactams with different R1 side chains, we show that azlocillin has greater affinity for Δ1-36 rPBP5 than piperacillin and ampicillin (apparent

K
i

= 7 ± 0.3 μM, compared to 36 ± 3 and 51 ± 10 μM, respectively). Azlocillin also exhibits the most rapid acylation rate (apparent

k
2

= 15 ± 4 M
−1
s
−1
). Meropenem demonstrates an affinity for Δ1-36 rPBP5 comparable to that of ampicillin (apparent

K
i

= 51 ± 15 μM) but is slower at acylating (apparent

k
2

= 0.14 ± 0.02 M
−1
s
−1
). This characterization defines important structure-activity relationships for this clinically relevant type II transpeptidase, shows that the rate of formation of the acyl-enzyme is an essential factor determining the efficacy of a β-lactam, and suggests that the specific side chain interactions of β-lactams could be modified to improve inactivation of resistant PBPs.
Conservation of Amino Acids in Human Rhinovirus 3C Protease Correlates with Broad-Spectrum Antiviral Activity of Rupintrivir, a Novel Human Rhinovirus 3C Protease Inhibitor
Authors: Binford S. L. , Maldonado F. , Brothers M. A. , Weady P. T. , Zalman L. S. , Meador J. W. , Matthews D. A. , Patick A. K. 
Published: January 2005

ABSTRACTThe picornavirus 3C protease is required for the majority of proteolytic cleavages that occur during the viral life cycle. Comparisons of published amino acid sequences from 6 human rhinoviruses (HRV) and 20 human enteroviruses (HEV) show considerable variability in the 3C protease-coding region but strict conservation of the catalytic triad residues. Rupintrivir (formerly AG7088) is an irreversible inhibitor of HRV 3C protease with potent in vitro activity against all HRV serotypes (48 of 48), HEV strains (4 of 4), and untyped HRV field isolates (46 of 46) tested. To better understand the relationship between in vitro antiviral activity and 3C protease-rupintrivir binding interactions, we performed nucleotide sequence analyses on an additional 21 HRV serotypes and 11 HRV clinical isolates. Antiviral activity was also determined for 23 HRV clinical isolates and four additional HEV strains. Sequence comparison of 3C proteases (n= 58) show that 13 and 11 of the 14 amino acids that are involved in side chain interactions with rupintrivir are strictly conserved among HRV and HEV, respectively. These sequence analyses are consistent with the comparable in vitro antiviral potencies of rupintrivir against all HRV serotypes, HRV isolates, and HEV strains tested (50% effective concentration range, 3 to 183 nM;n= 125). In summary, the conservation of critical amino acid residues in 3C protease and the observation of potent, broad-spectrum antipicornavirus activity of rupintrivir highlight the advantages of 3C protease as an antiviral target.
Provitamin B
5
(Pantothenol) Inhibits Growth of the Intraerythrocytic Malaria Parasite
Authors: Saliba Kevin J. , Ferru Isabelle , Kirk Kiaran 
Published: January 2005

ABSTRACT

Pantothenic acid, a precursor of the crucial enzyme cofactor coenzyme A, is one of a relatively few nutrients for which the intraerythrocytic parasite has an absolute and acute requirement from the external medium. In some organisms the provitamin pantothenol can serve as a source of pantothenic acid; however, this was not the case for the human malaria parasite
Plasmodium falciparum
. Instead, pantothenol inhibited the in vitro growth of
P. falciparum
via a mechanism that involves competition with pantothenate and which can be attributed to inhibition of the parasite's pantothenate kinase. Oral administration of pantothenol to mice infected with the murine parasite
Plasmodium vinckei vinckei
resulted in a significant inhibition of parasite proliferation. This study highlights the potential of the coenzyme A biosynthesis pathway in general, and pantothenate kinase in particular, as an antimalarial drug target.
Pharmacokinetics and Pharmacodynamics of Cefpirome in Subcutaneous Adipose Tissue of Septic Patients
Authors: Sauermann Robert , Delle-Karth Georg , Marsik Claudia , Steiner Ilka , Zeitlinger Markus , Mayer-Helm Bernhard X. , Georgopoulos Apostolos , Müller Markus , Joukhadar Christian 
Published: January 2005

ABSTRACT

The objective of the present study was to evaluate whether cefpirome, a member of the latest class of broad-spectrum cephalosporins, sufficiently penetrates subcutaneous adipose tissue in septic patients. After the administration of the drug at 2 g, tissue cefpirome concentrations in septic patients (
n
= 11) and healthy controls (
n
= 7) were determined over a period of 4 h by means of microdialysis. To assess the antibacterial effect of cefpirome at the target site, the measured pharmacokinetic profiles were simulated in vitro with select strains of
Staphylococcus aureus
and
Pseudomonas aeruginosa
. The tissue penetration of cefpirome was significantly impaired in septic patients compared with that in healthy subjects. For subcutaneous adipose tissue, the area under the concentration-versus-time curve values from 0 to 240 min were 13.11 ± 5.20 g · min/liter in healthy subjects and 6.90 ± 2.56 g · min/liter in septic patients (
P
< 0.05). Effective bacterial growth inhibition was observed in all in vitro simulations. This was attributed to the significantly prolonged half-life in tissue (
P
< 0.05), which kept the tissue cefpirome levels above the MICs for relevant pathogens for extended periods in the septic group. By consideration of a dosing interval of 8 h, the values for the time above MIC (
T
> MIC) in tissue were greater than 60% for pathogens for which the MIC was ≤4 mg/liter in all septic patients. The present data indicate that cefpirome is an appropriate agent for the treatment of soft tissue infections in septic patients. However, due to the high interindividual variability of the pharmacokinetics of cefpirome in tissue, dosing intervals of not more than 8 h should be preferred to ensure that susceptible bacterial strains are killed in each patient.
Comparison of the Antiviral Activities of Alkoxyalkyl and Alkyl Esters of Cidofovir against Human and Murine Cytomegalovirus Replication In Vitro
Authors: Wan William B. , Beadle James R. , Hartline Caroll , Kern Earl R. , Ciesla Stephanie L. , Valiaeva Nadejda , Hostetler Karl Y. 
Published: January 2005

ABSTRACT
Alkoxyalkyl esters of cidofovir (CDV) have substantially greater antiviral activity and selectivity than unmodified CDV against herpesviruses and orthopoxviruses in vitro. Enhancement of antiviral activity was also noted when cyclic CDV was esterified with alkoxyalkanols. In vitro antiviral activity of the most active analogs against human cytomegalovirus (HCMV) and orthopoxviruses was increased relative to CDV up to 1,000- or 200-fold, respectively. Alkyl chain length and linker structure are important potential modifiers of antiviral activity and selectivity. In this study, we synthesized a series of alkoxyalkyl esters of CDV or cyclic CDV with alkyl chains from 8 to 24 atoms and having linker moieties of glycerol, propanediol, and ethanediol. We also synthesized alkyl esters of CDV which lack the linker to determine if the alkoxyalkyl linker moiety is required for activity. The new compounds were evaluated in vitro against HCMV and murine CMV (MCMV). CDV or cyclic CDV analogs both with and without linker moieties were highly active against HCMV and MCMV, and their activities were strongly dependent on chain length. The most active compounds had 20 atoms esterified to the phosphonate of CDV. Both alkoxypropyl and alkyl esters of CDV provided enhanced antiviral activities against CMV in vitro. Thus, the oxypropyl linker moiety is not required for enhanced activity. CDV analogs having alkyl ethers linked to glycerol or ethanediol linker groups also demonstrated increased activity against CMV.
Prevalence and Subtypes of Ciprofloxacin-Resistant
Campylobacter
spp. in Commercial Poultry Flocks before, during, and after Treatment with Fluoroquinolones
Authors: Humphrey Tom J. , Jørgensen Frieda , Frost Jennifer A. , Wadda Haddy , Domingue Gil , Elviss Nicola C. , Griggs Deborah J. , Piddock Laura J. V. 
Published: January 2005

ABSTRACT

Five commercial broiler chicken flocks were treated with either difloxacin or enrofloxacin for a clinically relevant infection, as instructed by a veterinarian. Campylobacters were isolated from individual fecal samples and from samples associated with the broiler environment before, during, and after treatment. Ciprofloxacin-resistant
Campylobacter jejuni
and/or
C. coli
strains were detected pretreatment in four flocks, but they constituted a very small proportion of the campylobacters present. When the broilers were treated with a fluoroquinolone, a rapid increase in the proportion of ciprofloxacin-resistant campylobacters was observed. During treatment nearly 100% of campylobacters were resistant, and in some flocks a high proportion of resistant strains persisted for up to 4 weeks after treatment. Prior to treatment a variety of campylobacter subtypes were present. During and after treatment considerable changes in both species and subtype prevalence were observed, but no single fluoroquinolone-resistant clone became dominant. Instead, resistant
C. coli
strains or a mixture of resistant
C. coli
and
C. jejuni
strains became dominant, whereas susceptible
C. jejuni
strains had usually been dominant prior to treatment. The resistant subtypes which emerged and became dominant were not always the same as those detected pretreatment. The persistence of resistant strains for up to 4 weeks posttreatment has important implications for any strategy designed to avoid the introduction of such strains into the food chain.
Altered NADH/NAD
+
Ratio Mediates Coresistance to Isoniazid and Ethionamide in Mycobacteria
Authors: Vilchèze Catherine , Weisbrod Torin R. , Chen Bing , Kremer Laurent , Hazbón Manzour H. , Wang Feng , Alland David , Sacchettini James C. , Jacobs William R. 
Published: January 2005

ABSTRACT

The front-line antituberculosis drug isoniazid (INH) and the related drug ethionamide (ETH) are prodrugs that upon activation inhibit the synthesis of mycolic acids, leading to bactericidal activity. Coresistance to INH and ETH can be mediated by dominant mutations in the target gene
inhA
, encoding an enoyl-ACP reductase, or by recessive mutations in
ndh
, encoding a type II NADH dehydrogenase (NdhII). To address the mechanism of resistance mediated by the latter, we have isolated novel
ndh
mutants of
Mycobacterium smegmatis
and
Mycobacterium bovis
BCG. The
M. smegmatis ndh
mutants were highly resistant to INH and ETH, while the
M. bovis
BCG mutants had low-level resistance to INH and ETH. All mutants had defects in NdhII activity resulting in an increase in intracellular NADH/NAD
+
ratios. Increasing NADH levels were shown to protect InhA against inhibition by the INH-NAD adduct formed upon INH activation. We conclude that
ndh
mutations mediate a novel mechanism of resistance by increasing the NADH cellular concentration, which competitively inhibits the binding of INH-NAD or ETH-NAD adduct to InhA.
Caspofungin Inhibits
Rhizopus oryzae
1,3-β-
d
-Glucan Synthase, Lowers Burden in Brain Measured by Quantitative PCR, and Improves Survival at a Low but Not a High Dose during Murine Disseminated Zygomycosis
Authors: Ibrahim Ashraf S. , Bowman Joel C. , Avanessian Valentina , Brown Keturah , Spellberg Brad , Edwards John E. , Douglas Cameron M. 
Published: January 2005

ABSTRACT

Rhizopus oryzae
is the most common cause of zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-β-
d
-glucan synthase [GS]) against the agents of zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that
R. oryzae
has both an
FKS
gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of
R. oryzae
. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of
R. oryzae
when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against
R. oryzae
in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against zygomycosis merits further investigation.
Multiechinocandin- and Multiazole-ResistantCandida parapsilosisIsolates Serially Obtained during Therapy for Prosthetic Valve Endocarditis
Authors: Moudgal Varsha , Little Tania , Boikov Dina , Vazquez Jose A. 
Published: January 2005

ABSTRACTEchinocandins are approved for the treatment of candidal infections. In vitro they have been shown to be less potent against strains ofCandida parapsilosisthan against otherCandidaspp. This is the first case report describing the development of a secondary multidrug (echinocandin-azole)-resistantCandidastrain during therapy.
Detection of KPC Carbapenem-Hydrolyzing Enzymes in
Enterobacter
spp. from Brooklyn, New York
Authors: Bratu Simona , Landman David , Alam Maqsood , Tolentino Elaine , Quale John 
Published: January 2005

ABSTRACT

Enterobacter
spp. are rarely resistant to carbapenems. In this report, one
Enterobacter
sp. isolate possessed
bla
KPC-3
and two possessed
bla
KPC-2
. For all three strains, the imipenem MICs were dependent on the inoculum and testing method; two were reported by the clinical laboratories to be carbapenem susceptible. Improved detection methods will be necessary to identify these enzymes.
Interspecies Recombination in Type II Topoisomerase Genes Is Not a Major Cause of Fluoroquinolone Resistance in Invasive
Streptococcus pneumoniae
Isolates in the United States
Authors: Pletz Mathias W. R. , McGee Lesley , Beall Bernard , Whitney Cynthia G. , Klugman Keith P. 
Published: January 2005

ABSTRACT

Mutations in the topoisomerase type II enzymes account for fluoroquinolone resistance in
Streptococcus pneumoniae
. These mutations can arise spontaneously or be transferred by intraspecies or interspecies recombination, primarily with viridans streptococci. We analyzed the nucleotide sequences of the quinolone resistance-determining regions of 49 invasive levofloxacin-resistant pneumococcal isolates and did not find any evidence for interspecies recombination.
The Biocide Triclosan Selects
Stenotrophomonas maltophilia
Mutants That Overproduce the SmeDEF Multidrug Efflux Pump
Authors: Sanchez Patricia , Moreno Eduardo , Martinez Jose L. 
Published: January 2005

ABSTRACT

The possibility that triclosan selects
Stenotrophomonas maltophilia
mutants overexpressing the multidrug resistance pump SmeDEF is analyzed. Five out of 12 triclosan-selected mutants were less susceptible to antibiotics than the wild-type strain and overproduced SmeDEF. Results are discussed in relation to current debates on the potential selection of antibiotic-resistant bacteria by household biocides.
Rapid Acquisition of Stable Azole Resistance by
Candida glabrata
Isolates Obtained before the Clinical Introduction of Fluconazole
Authors: Borst Annemarie , Raimer Maria T. , Warnock David W. , Morrison Christine J. , Arthington-Skaggs Beth A. 
Published: January 2005

ABSTRACT

Five azole-susceptible
Candida glabrata
isolates obtained before 1975 became resistant to fluconazole, itraconazole, and voriconazole within 4 days of in vitro fluconazole exposure. This cross-resistance was stable for at least 4 months after removal of fluconazole and was associated with increased
CgCDR1
and
CgCDR2
expression.
The
aadB
Gene Cassette Is Associated with
bla
SHV
Genes in
Klebsiella
Species Producing Extended-Spectrum β-Lactamases
Authors: Jones Louisa A. , McIver Christopher J. , Kim Mi-Jurng , Rawlinson William D. , White Peter A. 
Published: January 2005

ABSTRACT

Integrons were detected in 37 (72.5%) of 51
Klebsiella
spp. producing extended-spectrum beta-lactamases by PCR with primers that targeted integrase genes and cassette regions. PCR and amplicon sequencing of the cassette regions revealed
aadB
and
aadA2
gene cassettes that confer resistance to a range of aminoglycosides.
aadB
was associated with a class 1 integron on a 28-kb plasmid, pES1, that also contained
bla
SHV-12
and IS
26
.
In Vitro Antileishmanial Activity of Nicotinamide
Authors: Sereno D. , Alegre A. Monte , Silvestre R. , Vergnes B. , Ouaissi A. 
Published: January 2005

ABSTRACT

Our study represents the first report demonstrating the antileishmanial activity of nicotinamide (NAm), a form of vitamin B
3
. A 5 mM concentration of NAm significantly inhibited the intracellular growth of
Leishmania
amastigotes and the NAD-dependent deacetylase activity carried by parasites overexpressing
Leishmania major
SIR2 (LmSIR2). However, the transgenic parasites were as susceptible as the wild-type parasites to NAm-induced cell growth arrest. Therefore, we conclude that NAm inhibits leishmanial growth and that overexpression of LmSIR2 does not overcome this inhibition. The mechanism of the inhibition is not defined but may include other in vivo targets. NAm may thus represent a new antileishmanial agent which could potentially be used in combination with other drugs during therapy.
Antibiotic Resistance in Diarrheagenic
Escherichia coli
and
Shigella
Strains Isolated from Children in Hanoi, Vietnam
Authors: Nguyen Trung Vu , Le Phung Van , Le Chinh Huy , Weintraub Andrej 
Published: January 2005

ABSTRACT

The MICs for 162 diarrheagenic
Escherichia coli
strains and 28
Shigella
strains were determined on the basis of NCCLS guidelines. More than 75% of the strains were resistant to ampicillin, chloramphenicol (53.6% of
Shigella
strains), and trimethoprim-sulfamethoxazole. Multiresistance was detected in 89.5% of
E. coli
strains and 78.6% of
Shigella
strains.
Elucidation of Essential and Nonessential Genes in the
Haemophilus influenzae
Rd Cell Wall Biosynthetic Pathway by Targeted Gene Disruption
Authors: Trepod Catherine M. , Mott John E. 
Published: January 2005

ABSTRACT

Targeted gene disruption by in vitro transposon mutagenesis has been used to identify the genes required for biosynthesis of the
Haemophilus influenzae
Rd cell wall under standard cultivation conditions. Of the 28 genes known to be associated with the cell wall biosynthetic pathway, 14 were determined to be essential.
Distribution of Subclasses
mefA
and
mefE
of the
mefA
Gene among Clinical Isolates of Macrolide-Resistant (M-Phenotype)
Streptococcus pneumoniae
, Viridans Group Streptococci, and
Streptococcus pyogenes
Authors: Ardanuy Carmen , Tubau Fe , Liñares Josefina , Domínguez María Angeles , Pallarés Román , Martín Rogelio 
Published: January 2005

ABSTRACT

The distribution of subclasses
mefA
and
mefE
of the
mefA
gene among 116 M-phenotype streptococci was as follows: pneumococci (38 strains had
mefE
and 4
mefA
), viridans streptococci (49
mefE
and 1
mefA
), and
Streptococcus pyogenes
(24
mefA
). Spain
9V
-3-14 and England
14
-9 clones of serotype 14 were dominant among pneumococci.