bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected Enzyme TEM-126: Role of Mutation Asp179Glu
Authors: Delmas J. , Robin F. , Bittar F. , Chanal C. , Bonnet R. 
Published: September 2005

ABSTRACT

The clinical isolate
Escherichia coli
CF884 exhibited low-level resistance to ceftazidime (4 μg/ml) by a positive double-disk synergy test and apparent susceptibility to cefuroxime, cefotaxime, cefepime, cefpirome, and aztreonam. The enzyme implicated in this phenotype was a novel 180-kb plasmid-encoded TEM-type extended-spectrum β-lactamase designated TEM-126 which harbors the mutations Asp179Glu and Met182Thr. TEM-126 exhibited significant hydrolytic activity (
k
cat
, 2 s
−1
) and a

K
m

value of 82 μM against ceftazidime. Molecular dynamics simulations suggested that the substitution Asp179Glu induces subtle conformational changes to the omega loop which may favor the insertion of ceftazidime in the binding site and the correct positioning of the crucial residue Glu166. Overall, these results highlight the remarkable plasticity of TEM enzymes, which can expand their activity against ceftazidime by the addition of one carbon atom in the side chain of residue 179.
Sensitivity of
Candida albicans
Germ Tubes and Biofilms to Photofrin-Mediated Phototoxicity
Authors: Chabrier-Roselló Yeissa , Foster Thomas H. , Pérez-Nazario Nelissa , Mitra Soumya , Haidaris Constantine G. 
Published: September 2005

ABSTRACT

Treatment of mucocutaneous and cutaneous
Candida albicans
infections with photosensitizing agents and light, termed photodynamic therapy (PDT), offers an alternative to conventional treatments. Initial studies using the clinically approved photosensitizer Photofrin demonstrated the susceptibility of
C. albicans
to its photodynamic effects. In the present study, we have further refined parameters for Photofrin-mediated photodynamic action against
C. albicans
and examined whether mechanisms commonly used by microorganisms to subvert either antimicrobial oxidative defenses or antimicrobial therapy, including biofilm formation, were operative. In buffer and defined medium, germ tubes preloaded with Photofrin retained their photosensitivity for up to 2 hours, indicating the absence of degradation or export of Photofrin by the organism. The addition of serum resulted in a gradual loss of photosensitivity over 2 hours. In contrast to an adaptive response by germ tubes to oxidative stress by hydrogen peroxide, there was no adaptive response to singlet oxygen-mediated stress by photodynamic action.
C. albicans
biofilms were sensitive to Photofrin-mediated phototoxicity in a dose-dependent manner. Finally, the metabolic activity of
C. albicans
biofilms following photodynamic insult was significantly lower than that of biofilms treated with amphotericin B for the same time period. These results demonstrate that several of the mechanisms microorganisms use to subvert either antimicrobial oxidative defenses or antimicrobial therapy are apparently not operative during Photofrin-mediated photodynamic treatment of
C. albicans
. These observations provide support and rationale for the continued investigation of PDT as an adjunctive, or possibly alternative, mode of therapy against cutaneous and mucocutaneous candidiasis.
Mutations Conferring Resistance to a Hepatitis C Virus (HCV) RNA-Dependent RNA Polymerase Inhibitor Alone or in Combination with an HCV Serine Protease Inhibitor In Vitro
Authors: Mo Hongmei , Lu Liangjun , Pilot-Matias Tami , Pithawalla Ron , Mondal Rubina , Masse Sherie , Dekhtyar Tatyana , Ng Teresa , Koev Gennadiy , Stoll Vincent , Stewart Kent D. , Pratt John , Donner Pam , Rockway Todd , Maring Clarence , Molla Akhteruzzaman 
Published: September 2005

ABSTRACTCompounds A-782759 (anN-1-aza-4-hydroxyquinolone benzothiadiazine) and BILN-2061 are specific anti-hepatitis C virus (HCV) agents that inhibit the RNA-dependent RNA polymerase and the NS3 serine protease, respectively. Both compounds display potent activity against HCV replicons in tissue culture. In order to characterize the development of resistance to these anti-HCV agents, HCV subgenomic 1b-N replicon cells were cultured with A-782759 alone or in combination with BILN-2061 at concentrations 10 times above their corresponding 50% inhibitory concentrations in the presence of neomycin. Single substitutions in the NS5B polymerase gene (H95Q, N411S, M414L, M414T, or Y448H) resulted in substantial decreases in susceptibility to A-782759. Similarly, replicons containing mutations in the NS5B polymerase gene (M414L or M414T), together with single mutations in the NS3 protease gene (A156V or D168V), conferred high levels of resistance to both A-782759 and BILN-2061. However, the A-782759-resistant mutants remained susceptible to nucleoside and two other classes of nonnucleoside NS5B polymerase inhibitors, as well as interferon. In addition, we found that the frequency of replicons resistant to both compounds was significantly lower than the frequency of resistance to the single compound. Furthermore, the dually resistant mutants displayed significantly reduced replication capacities compared to the wild-type replicon. These findings provide strategic guidance for the future treatment of HCV infection.
Molecular Evolution Perspectives on Intraspecific Lateral DNA Transfer of Topoisomerase and Gyrase Loci in
Streptococcus pneumoniae
, with Implications for Fluoroquinolone Resistance Development and Spread
Authors: Stanhope Michael J. , Walsh Stacey L. , Becker Julie A. , Italia Michael J. , Ingraham Karen A. , Gwynn Michael N. , Mathie Tom , Poupard James A. , Miller Linda A. , Brown James R. , Amrine-Madsen Heather 
Published: September 2005

ABSTRACT

Fluoroquinolones are an important class of antibiotics for the treatment of infections arising from the gram-positive respiratory pathogen
Streptococcus pneumoniae
. Although there is evidence supporting interspecific lateral DNA transfer of fluoroquinolone target loci, no studies have specifically been designed to assess the role of intraspecific lateral transfer of these genes in the spread of fluoroquinolone resistance. This study involves a comparative evolutionary perspective, in which the evolutionary history of a diverse set of
S. pneumoniae
clinical isolates is reconstructed from an expanded multilocus sequence typing data set, with putative recombinants excluded. This control history is then assessed against networks of each of the four fluoroquinolone target loci from the same isolates. The results indicate that although the majority of fluoroquinolone target loci from this set of 60 isolates are consistent with a clonal dissemination hypothesis, 3 to 10% of the sequences are consistent with an intraspecific lateral transfer hypothesis. Also evident were examples of interspecific transfer, with two isolates possessing a
parE
-
parC
gene region arising from viridans group streptococci. The Spain 23F-1 clone is the most dominant fluoroquinolone-nonsusceptible clone in this set of isolates, and the analysis suggests that its members act as frequent donors of fluoroquinolone-nonsusceptible loci. Although the majority of fluoroquinolone target gene sequences in this set of isolates can be explained on the basis of clonal dissemination, a significant number are more parsimoniously explained by intraspecific lateral DNA transfer, and in situations of high
S. pneumoniae
population density, such events could be an important means of resistance spread.
High-Level Chromosomally Mediated Tetracycline Resistance inNeisseria gonorrhoeaeResults from a Point Mutation in therpsJGene Encoding Ribosomal Protein S10 in Combination with themtrRandpenBResistance Determinants
Authors: Hu Mei , Nandi Sobhan , Davies Christopher , Nicholas Robert A. 
Published: September 2005

ABSTRACTNeisseria gonorrhoeaebecomes resistant to tetracycline by two major mechanisms: expression of a plasmid-encoded TetM protein and mutations in endogenous genes (chromosomally mediated resistance). Early studies by Sparling and colleagues (P. F. Sparling F. A. J. Sarubbi, and E. Blackman, J. Bacteriol. 124:740-749, 1975) demonstrated that three genes were involved in high-level chromosomally mediated tetracycline resistance (MIC of tetracycline ≥ 2 μg/ml):ery-2(now referred to asmtrR),penB, andtet-2. While the identities of the first two genes are known, thetet-2gene has not been identified. We cloned thetet-2gene, which confers tetracycline resistance, from tetracycline-resistant clinical isolateN. gonorrhoeaeFA6140 and show that resistance is due to a single point mutation (Val-57 to Met) in therpsJgene (rpsJ1) encoding ribosomal protein S10. Moreover, the identical mutation was found in six distinct tetracycline-resistant clinical isolates in which the MIC of tetracycline was ≥2 μg/ml. Site-saturation mutagenesis of the codon for Val-57 identified two other amino acids (Leu and Gln) that conferred identical levels of resistance as the Met-57 mutation. The mutation maps to the vertex of a loop in S10 that is near the aminoacyl-tRNA site in the structure of the 30S ribosomal subunit fromThermus thermophilus, and the residue equivalent to Val-57 inT. thermophilusS10, Lys-55, is within 8 to 9 Å of bound tetracycline. These data suggest that large noncharged amino acids alter the rRNA structure near the tetracycline-binding site, leading to a lower affinity of the antibiotic.
Oral Therapy Using Nanoparticle-Encapsulated Antituberculosis Drugs in Guinea Pigs Infected with
Mycobacterium tuberculosis
Authors: Johnson Christine M. , Pandey Rajesh , Sharma Sadhna , Khuller G. K. , Basaraba Randall J. , Orme Ian M. , Lenaerts Anne J. 
Published: September 2005

ABSTRACT

We evaluated the efficacy of nanoparticle-encapsulated antituberculosis drugs administered every 10 days versus that of daily nonencapsulated drugs against
Mycobacterium tuberculosis
aerosol infection in guinea pigs. Both treatments significantly reduced the bacterial count and lung histopathology, suggesting that the nanoparticle drug delivery system has potential in intermitted treatment of tuberculosis.
Efficacy of Telavancin (TD-6424), a Rapidly Bactericidal Lipoglycopeptide with Multiple Mechanisms of Action, in a Murine Model of Pneumonia Induced by Methicillin-Resistant
Staphylococcus aureus
Authors: Reyes Noe , Skinner Robert , Kaniga Koné , Krause Kevin M. , Shelton Josephine , Obedencio Glenmar P. , Gough Alexander , Conner Michael , Hegde Sharath S. 
Published: September 2005

ABSTRACT

The efficacy of telavancin, a bactericidal lipoglycopeptide, was compared to that of vancomycin and linezolid against methicillin-resistant
Staphylococcus aureus
(MRSA) in a murine pneumonia model. Telavancin produced greater reductions in lung bacterial titer and mortality than did vancomycin and linezolid at human doses equivalent to those described by the area under the concentration-time curve. These results suggest the potential utility of telavancin for treatment of MRSA pneumonia.
The
erm
(T) Gene Is Flanked by IS
1216V
in Inducible Erythromycin-Resistant
Streptococcus gallolyticus
subsp.
pasteurianus
Authors: Tsai Jui-Chang , Hsueh Po-Ren , Chen Hsiao-Jan , Tseng Sung-Pin , Chen Pei-Yu , Teng Lee-Jene 
Published: September 2005

ABSTRACT

We investigated the sequence and the genetic context of the
erm
(T) gene in six inducible erythromycin-resistant
Streptococcus gallolyticus
subsp.
pasteurianus
(formerly
S. bovis
biotype II.2) isolates. In all isolates, the
erm
(T) genes were flanked by two IS
1216V
-like elements with the same polarity and were found to be inserted in the chromosome.
parC
Mutations in Fluoroquinolone-Resistant
Borrelia burgdorferi
Authors: Galbraith Kendal M. , Ng Amanda C. , Eggers Betsy J. , Kuchel Craig R. , Eggers Christian H. , Samuels D. Scott 
Published: September 2005

ABSTRACT

We have isolated in vitro fluoroquinolone-resistant mutants of the Lyme disease agent,
Borrelia burgdorferi
. Mutations in
parC
, which encodes a subunit of topoisomerase IV, were associated with loss of susceptibility to sparfloxacin, moxifloxacin, and Bay-Y3118, but not ciprofloxacin. This is the first description of fluoroquinolone resistance in the spirochete phylum.
Efficacy of 2-(3,4-Dimethyl-2,5-Dihydro-1H-Pyrrole-2-yl)-1-Methylethyl Pentanoate in a Murine Model of Invasive Aspergillosis
Authors: Dabur Rajesh , Diwedi S. K. , Yadav V. , Mishra V. , Singh Rambir , Singh H. , Sharma G. L. 
Published: September 2005

ABSTRACT

2-(3,4-Dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, an antifungal compound, was found to be nontoxic to RAW cells up to a concentration of 312.5 μg/ml, whereas amphotericin B was lethal to all cells at 37.5 μg/ml. The treatment of
Aspergillus fumigatus
-infected mice with a dose of 200.0 mg of compound/kg of body weight increased their survival rate by 60%, with a decrease in CFU in organ tissues. The protection afforded by the compound against experimental aspergillosis was found to be dose dependent.
Penetration of Piperacillin and Tazobactam into Inflamed Soft Tissue of Patients with Diabetic Foot Infection
Authors: Legat F. J. , Krause R. , Zenahlik P. , Hoffmann C. , Scholz S. , Salmhofer W. , Tscherpel J. , Tscherpel T. , Kerl H. , Dittrich P. 
Published: September 2005

ABSTRACT
We investigated the pharmacokinetics of piperacillin and tazobactam in the extracellular space fluid of inflamed soft tissues of six patients with diabetic foot infection using in vivo microdialysis and found similar penetration for piperacillin but not for tazobactam into inflamed and noninflamed soft tissue.
Interaction of the MexA and MexB Components of the MexAB-OprM Multidrug Efflux System of
Pseudomonas aeruginosa
: Identification of MexA Extragenic Suppressors of a T578I Mutation in MexB
Authors: Nehme Dominic , Poole Keith 
Published: September 2005

ABSTRACT

A T578I mutation in MexB compromised the protein's contribution to antimicrobial resistance and negatively impacted its interaction with MexA. Mutations causing single amino acid changes in the C-terminal domain of MexA (R221H, L245F, E254K, and V259I) suppressed the antimicrobial susceptibility of a MexB
T578I
-expressing
Pseudomonas aeruginosa
strain and restored a MexA interaction with MexB
T578I
. These data confirm the importance of the MexA C-terminal region in MexB binding and the likely significance of the region surrounding T587I of MexB in MexA interaction.
Macrolide Resistance Mediated by a
Bifidobacterium breve
Membrane Protein
Authors: Margolles Abelardo , Moreno José Antonio , van Sinderen Douwe , de los Reyes-Gavilán Clara G. 
Published: September 2005

ABSTRACT

A gene coding for a hypothetical membrane protein from
Bifidobacterium breve
was expressed in
Lactococcus lactis
. Immunoblotting demonstrated that this protein is located in the membrane. Phenotypical changes in sensitivity towards 21 antibiotics were determined. The membrane protein-expressing cells showed higher levels of resistance to several macrolides.
Contribution of Mutation at Amino Acid 45 of AcrR to
acrB
Expression and Ciprofloxacin Resistance in Clinical and Veterinary
Escherichia coli
Isolates
Authors: Webber Mark A. , Talukder Ashraf , Piddock Laura J. V. 
Published: September 2005

ABSTRACT

Fluoroquinolone-resistant
Escherichia coli
isolates which overexpressed
acrB
and had a substitution at amino acid 45 of AcrR were complemented with wild-type
acrR
. Complementation led to increased sensitivity to ciprofloxacin and to ethidium bromide, suggesting that mutation at amino acid 45 of AcrR contributes to ciprofloxacin resistance.
Limited Polymorphism in the Dihydropteroate Synthetase Gene (
dhps
) of
Plasmodium vivax
Isolates from Thailand
Authors: Imwong Mallika , Pukrittayakamee Sasithon , Cheng Qin , Moore Catrin , Looareesuwan Sornchai , Snounou Georges , White Nicholas J. , Day Nicholas P. J. 
Published: September 2005

ABSTRACT

The
dhps
sequences of 55
Plasmodium vivax
isolates (39 from Thailand and 16 from elsewhere) revealed mutant Pv
dhps
at codons 383 and/or 553 (A → G) in 33 isolates, all from Thailand. Mutations of Pv
dhps
and Pv
dhfr
were correlated. Multiple mutations were associated with high-grade sulfadoxine-pyrimethamine resistance.
Clevudine Inhibits Hepatitis Delta Virus Viremia: a Pilot Study of Chronically Infected Woodchucks
Authors: Casey John , Cote Paul J. , Toshkov Illia A. , Chu Chung K. , Gerin John L. , Hornbuckle William E. , Tennant Bud C. , Korba Brent E. 
Published: September 2005

ABSTRACTIn a small controlled study, clevudine, a potent inhibitor of hepadnaviruses, including hepatitis B virus and woodchuck hepatitis virus, suppressed hepatitis delta virus (HDV) viremia in chronically infected woodchucks. Suppression was correlated with the marked reduction of woodchuck hepatitis virus surface antigen in individual animals, consistent with the concept that repression of surface antigen expression may be a useful antiviral strategy for HDV.
Genetic and Enzymatic Properties of Metallo-β
-
Lactamase VIM-5 from a Clinical Isolate of
Enterobacter cloacae
Authors: Gacar Gulcin G. , Midilli Kenan , Kolayli Fetiye , Ergen Kivanc , Gundes Sibel , Hosoglu Salih , Karadenizli Aynur , Vahaboglu Haluk 
Published: September 2005

ABSTRACT

A VIM-5-producing
Enterobacter cloacae
isolate (EDV/1) was identified in a collection of clinical strains stored before 2002. The gene,
bla
VIM-5
, was located on a 2,712-bp BamHI-HindIII fragment of a 23-kbp (approximately) nonconjugative plasmid (pEDV5) in a class 1 integron as a single gene cassette.
Low Rates of Cutaneous Adverse Reactions to Alcohol-Based Hand Hygiene Solution during Prolonged Use in a Large Teaching Hospital
Authors: Graham M. , Nixon R. , Burrell L. J. , Bolger C. , Johnson P. D. R. , Grayson M. L. 
Published: September 2005

ABSTRACT
We assessed cutaneous adverse reactions (CARs) to alcohol-based hand rub (ABHR) after the introduction of a hand hygiene culture change program at our institution. CARs were infrequent among exposed health care workers (HCWs) (13/2,750; 0.47%; 1 CAR per 72 years of HCW exposure) and were not influenced by the duration or intensity of ABHR use but were associated with the presence of irritant contact dermatitis.
Lower Nitric Oxide Susceptibility of Trivalent Antimony-Resistant Amastigotes ofLeishmania infantum
Authors: Holzmuller P. , Sereno D. , Lemesre J.-L. 
Published: September 2005

ABSTRACTWe previously documented the induction ofLeishmaniaamastigote apoptosis by trivalent antimony (SbIII) and nitric oxide (NO). We demonstrate here that SbIII-resistant amastigotes were resistant to NO toxicity when delivered extracellularly by NO donors or intracellularly via macrophage activation. Shared biochemical targets for SbIII and NO resistance inLeishmaniaare discussed.
Inhibition of Class D β-Lactamases by Acyl Phosphates and Phosphonates
Authors: Adediran S. A. , Nukaga Michiyoshi , Baurin Stéphane , Frère J.-M. , Pratt R. F. 
Published: September 2005

ABSTRACT
The susceptibility of typical class D β-lactamases to inhibition by acyl phosph(on)ates has been determined. To a large degree, these class D enzymes behaved very similarly to the class A TEM β-lactamase towards these reagents. Dibenzoyl phosphate stood out in both cases as a lead compound towards a new class of effective inhibitors.
In Vitro Activities of Doripenem and Comparator Agents against 364 Anaerobic Clinical Isolates
Authors: Wexler Hannah M. , Engel Adrian E. , Glass Daniel , Li Calida 
Published: September 2005

ABSTRACT

The in vitro activities of doripenem against 364 anaerobic isolates were measured and compared to those of ertapenem, imipenem, meropenem, ceftriaxone, and levofloxacin. All of the carbapenems were active against nearly all
Bacteroides fragilis
group isolates. Doripenem was either comparable to or slightly less active than imipenem and meropenem against most isolates but more active than the other penems against
Clostridium difficile
. Doripenem appears to have excellent activity against a broad range of anaerobes.
Intratypic Recombination among Lineages of Type 1 Vaccine-Derived Poliovirus Emerging during Chronic Infection of an Immunodeficient Patient
Authors: Yang Chen-Fu , Chen Hour-Young , Jorba Jaume , Sun Hui-Chih , Yang Su-Ju , Lee Hsiang-Chi , Huang Yhu-Chering , Lin Tzou-Yien , Chen Pei-Jer , Shimizu Hiroyuki , Nishimura Yorihiro , Utama Andi , Pallansch Mark , Miyamura Tatsuo , Kew Olen , Yang Jyh-Yuan 
Published: September 2005

ABSTRACT
We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.
Endocytosis Plays a Critical Role in Proteolytic Processing of the Hendra Virus Fusion Protein
Authors: Meulendyke Kelly Ann , Wurth Mark Allen , McCann Richard O. , Dutch Rebecca Ellis 
Published: September 2005

ABSTRACT

The Hendra virus fusion (F) protein is synthesized as a precursor protein, F
0
, which is proteolytically processed to the mature form, F
1
+F
2
. Unlike the case for the majority of paramyxovirus F proteins, the processing event is furin independent, does not require the addition of exogenous proteases, is not affected by reductions in intracellular Ca
2+
, and is strongly affected by conditions that raise the intracellular pH (C. T. Pager, M. A. Wurth, and R. E. Dutch, J. Virol.
78:
9154-9163, 2004). The Hendra virus F protein cytoplasmic tail contains a consensus motif for endocytosis, YXXΦ. To analyze the potential role of endocytosis in the processing and membrane fusion promotion of the Hendra virus F protein, mutation of tyrosine 525 to alanine (Hendra virus F Y525A) or phenylalanine (Hendra virus F Y525F) was performed. The rate of endocytosis of Hendra virus F Y525A was significantly reduced compared to that of the wild-type (wt) F protein, confirming the functional importance of the endocytosis motif. An intermediate level of endocytosis was observed for Hendra virus F Y525F. Surprisingly, dramatic reductions in the rate of proteolytic processing were observed for Hendra virus F Y525A, although initial transport to the cell surface was not affected. The levels of surface expression for both Hendra virus F Y525A and Hendra virus F Y525F were higher than that of the wt protein, and these mutants displayed enhanced syncytium formation. These results suggest that endocytosis is critically important for Hendra virus F protein cleavage, representing a new paradigm for proteolytic processing of paramyxovirus F proteins.