bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial Strain-to-Strain Variation in Pharmacodynamic Index Magnitude, a Hitherto Unconsidered Factor in Establishing Antibiotic Clinical Breakpoints
Authors: MacGowan Alasdair P. , Reynolds Rosy , Noel Alan R. , Bowker Karen E. 
Published: October 2009

ABSTRACT

Antibiotic pharmacodynamic modeling allows variations in pathogen susceptibility and human pharmacokinetics to be accounted for when considering antibiotic doses, potential bacterial pathogen targets for therapy, and clinical susceptibility breakpoints. Variation in the pharmacodynamic index (area-under-the-concentration curve to 24 h [AUC
24
]/MIC; maximum serum concentration of drug in the serum/MIC; time the serum concentration remains higher than the MIC [
T
> MIC]) is not usually considered. In an in vitro pharmacokinetic model of infection using a dose-ranging design, we established the relationship between AUC
24
/MIC and the antibacterial effect for moxifloxacin against 10 strains of
Staphylococcus aureus
. The distributions of AUC
24
/MIC targets for 24-h bacteriostatic effect and 1-log, 2-log, and 3-log drops in bacterial counts were used to calculate potential clinical breakpoint values, and these were compared with those obtained by the more conventional approach of taking a single AUC
24
/MIC target. Consideration of the AUC
24
/MIC as a distribution rather than a single value resulted in a lower clinical breakpoint.
In Vitro Pharmacodynamics of Levofloxacin and Other Aerosolized Antibiotics under Multiple Conditions Relevant to Chronic Pulmonary Infection in Cystic Fibrosis
Authors: King Paula , Lomovskaya Olga , Griffith David C. , Burns Jane L. , Dudley Michael N. 
Published: October 2009

ABSTRACT

The inhalational administration of antibiotics can provide high concentrations locally in the lungs of cystic fibrosis patients and, thus, can be useful for the treatment of chronic bacterial infections. The present study evaluated the in vitro activities of levofloxacin, ciprofloxacin, tobramycin, amikacin, and aztreonam against clinical isolates of
Pseudomonas aeruginosa
,
Burkholderia cepacia
complex,
Stenotrophomonas maltophilia
,
Alcaligenes xylosoxidans
, and
Staphylococcus aureus
from cystic fibrosis patients. Levofloxacin was the most potent antibiotic against all cystic fibrosis isolates tested, with MIC
90
s ranging from 8 to 32 μg/ml. Levofloxacin was more potent than the aminoglycosides and aztreonam against
P. aeruginosa
biofilms. Time-kill assays with drug concentrations achievable in sputum following aerosol administration showed that levofloxacin had the most rapid rate of killing among mucoid and nonmucoid isolates of
P. aeruginosa
. In contrast to tobramycin, the bactericidal activity of levofloxacin was not affected by sputum from cystic fibrosis patients. The results of the study show that the high concentrations of levofloxacin readily achievable in the lung following aerosol delivery may be useful for the management of pulmonary infections in patients with cystic fibrosis.
Effects of Subinhibitory Concentrations of Antibiotics on Colonization Factor Expression by Moxifloxacin-Susceptible and Moxifloxacin-Resistant
Clostridium difficile
Strains
Authors: Denève Cécile , Bouttier Sylvie , Dupuy Bruno , Barbut Frédéric , Collignon Anne , Janoir Claire 
Published: October 2009

ABSTRACT

Recent outbreaks of
Clostridium difficile
infection have been related to the emergence of the NAP1/027 epidemic strain. This strain demonstrates increased virulence and resistance to the C-8-methoxyfluoroquinolones gatifloxacin and moxifloxacin. These antibiotics have been implicated as major
C. difficile
infection-inducing agents. We investigated by real-time reverse transcription-PCR the impact of subinhibitory concentrations of ampicillin, clindamycin, ofloxacin, and moxifloxacin on the expression of genes encoding three colonization factors, the protease Cwp84, the high-molecular-weight S-layer protein, and the fibronectin-binding protein Fbp68. We have previously shown in six non-NAP1/027 moxifloxacin-susceptible strains that the presence of ampicillin or clindamycin induced an upregulation of these genes, whereas the presence of fluoroquinolones did not. The objective of this study was to analyze the expression of these genes under the same conditions in four NAP1/027 strains, one moxifloxacin susceptible and three moxifloxacin resistant. Two in vitro-selected moxifloxacin-resistant mutants were also analyzed. Moxifloxacin resistance was associated with the Thr82→Ile substitution in GyrA in all but one of the moxifloxacin-resistant strains. The expression of
cwp84
and
slpA
was strongly increased after culture with ampicillin or clindamycin in NAP1/027 strains. Interestingly, after culture with fluoroquinolones, the expression of
cwp84
and
slpA
was only increased in four moxifloxacin-resistant strains, including the NAP1/027 strains and one of the in vitro-selected mutants. The overexpression of
cwp84
was correlated with increased production of the protease Cwp84. The historical NAP1/027 moxifloxacin-susceptible strain and its mutant appear to be differently regulated by fluoroquinolones. Overall, fluoroquinolones appear to favor the expression of some colonization factor-encoding genes in resistant
C. difficile
strains. The fluoroquinolone resistance of the NAP1/027 epidemic strains could be considered an ecological advantage. This could also increase their colonization fitness and promote the infection.
New Small-Molecule Inhibitor Class Targeting Human Immunodeficiency Virus Type 1 Virion Maturation
Authors: Blair Wade S. , Cao Joan , Fok-Seang Juin , Griffin Paul , Isaacson Jason , Jackson R. Lynn , Murray Edward , Patick Amy K. , Peng Qinghai , Perros Manos , Pickford Chris , Wu Hua , Butler Scott L. 
Published: October 2009

ABSTRACT

A new small-molecule inhibitor class that targets virion maturation was identified from a human immunodeficiency virus type 1 (HIV-1) antiviral screen. PF-46396, a representative molecule, exhibits antiviral activity against HIV-1 laboratory strains and clinical isolates in T-cell lines and peripheral blood mononuclear cells (PBMCs). PF-46396 specifically inhibits the processing of capsid (CA)/spacer peptide 1 (SP1) (p25), resulting in the accumulation of CA/SP1 (p25) precursor proteins and blocked maturation of the viral core particle. Viral variants resistant to PF-46396 contain a single amino acid substitution in HIV-1 CA sequences (CAI201V), distal to the CA/SP1 cleavage site in the primary structure, which we demonstrate is sufficient to confer significant resistance to PF-46396 and 3-
O
-(3′,3′-dimethylsuccinyl) betulinic acid (DSB), a previously described maturation inhibitor. Conversely, a single amino substitution in SP1 (SP1A1V), which was previously associated with DSB in vitro resistance, was sufficient to confer resistance to DSB and PF-46396. Further, the CAI201V substitution restored CA/SP1 processing in HIV-1-infected cells treated with PF-46396 or DSB. Our results demonstrate that PF-46396 acts through a mechanism that is similar to DSB to inhibit the maturation of HIV-1 virions. To our knowledge, PF-46396 represents the first small-molecule HIV-1 maturation inhibitor that is distinct in chemical class from betulinic acid-derived maturation inhibitors (e.g., DSB), demonstrating that molecules of diverse chemical classes can inhibit this mechanism.
Mutations in Ribosomal Protein L3 Are Associated with Oxazolidinone Resistance in Staphylococci of Clinical Origin
Authors: Locke Jeffrey B. , Hilgers Mark , Shaw Karen Joy 
Published: October 2009

ABSTRACT

Following recent reports of ribosomal protein L3 mutations in laboratory-derived linezolid-resistant (LZD
r
)
Staphylococcus aureus
, we investigated whether similar mutations were present in LZD
r
staphylococci of clinical origin. Sequence analysis of a variety of LZD
r
isolates revealed two L3 mutations, ΔSer145 (
S. aureus
NRS127) and Ala157Arg (
Staphylococcus epidermidis
1653059), both occurring proximal to the oxazolidinone binding site in the peptidyl transferase center. The oxazolidinone torezolid maintained a ≥8-fold potency advantage over linezolid for both strains.
Phenotypic and Genotypic Characterization of
Enterobacteriaceae
with Decreased Susceptibility to Carbapenems: Results from Large Hospital-Based Surveillance Studies in China
Authors: Yang Qiwen , Wang Hui , Sun Hongli , Chen Hongbin , Xu Yingchun , Chen Minjun 
Published: October 2009

ABSTRACT

The resistance mechanism of 49
Enterobacteriaceae
isolates with decreased susceptibility to carbapenems collected from 2004 to 2008 at 16 teaching hospitals in China was investigated. Moderate- to high-level carbapenem resistance in most isolates was more closely associated with loss or decreased expression of both major porins combined with production of AmpC or extended-spectrum β-lactamase enzymes, while KPC-2, IMP-4, and IMP-8 carbapenemase production may lead to a low to moderate level of carbapenem resistance in
Enterobacteriaceae
in China.
Development of a Test System To Evaluate Procedures for Decontamination of Respirators Containing Viral Droplets
Authors: Vo Evanly , Rengasamy Samy , Shaffer Ronald 
Published: October 2009

ABSTRACT

The aim of this study was to develop a test system to evaluate the effectiveness of procedures for decontamination of respirators contaminated with viral droplets. MS2 coliphage was used as a surrogate for pathogenic viruses. A viral droplet test system was constructed, and the size distribution of viral droplets loaded directly onto respirators was characterized using an aerodynamic particle sizer. The sizes ranged from 0.5 to 15 μm, and the sizes of the majority of the droplets were the range from 0.74 to 3.5 μm. The results also showed that the droplet test system generated similar droplet concentrations (particle counts) at different respirator locations. The test system was validated by studying the relative efficiencies of decontamination of sodium hypochlorite (bleach) and UV irradiation with droplets containing MS2 virus on filtering facepiece respirators. It was hypothesized that more potent decontamination treatments would result in corresponding larger decreases in the number of viable viruses recovered from the respirators. Sodium hypochlorite doses of 2.75 to 5.50 mg/liter with a 10-min decontamination period resulted in approximately 3- to 4-log reductions in the level of MS2 coliphage. When higher sodium hypochlorite doses (≥8.25 mg/liter) were used with the same contact time that was used for the dilute solutions containing 2.75 to 5.50 mg/liter, all MS2 was inactivated. For UV decontamination at a wavelength of 254 nm, an approximately 3-log reduction in the level of MS2 virus was achieved with dose of 4.32 J/cm
2
(3 h of contact time with a UV intensity of 0.4 mW/cm
2
), while with higher doses of UV irradiation (≥7.20 J/cm
2
; UV intensity, 0.4 mW/cm
2
; contact times, ≥5 h), all MS2 was inactivated. These findings may lead to development of a standard method to test decontamination of respirators challenged by viral droplets.
Glycoprofiling Bifidobacterial Consumption of Galacto-Oligosaccharides by Mass Spectrometry Reveals Strain-Specific, Preferential Consumption of Glycans
Authors: Barboza Mariana , Sela David A. , Pirim Claire , LoCascio Riccardo G. , Freeman Samara L. , German J. Bruce , Mills David A. , Lebrilla Carlito B. 
Published: October 2009

ABSTRACT
Galacto-oligosaccharides (GOS) are versatile food ingredients that possess prebiotic properties. However, at present there is a lack of precise analytical methods to demonstrate specific GOS consumption by bifidobacteria. To better understand the role of GOS as prebiotics, purified GOS (pGOS) without disaccharides and monosaccharides was prepared and used in bacterial fermentation experiments. Growth curves showed that all bifidobacteria assayed utilized and grew on pGOS preparations. We used a novel mass spectrometry approach involving matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) to determine the composition of oligosaccharides in GOS syrup preparations. MALDI-FTICR analysis of spent fermentation media demonstrated that there was preferential consumption of selected pGOS species by different bifidobacteria. The approach described here demonstrates that MALDI-FTICR is a rapid-throughput tool for comprehensive profiling of oligosaccharides in GOS mixtures. In addition, the selective consumption of certain GOS species by different bifidobacteria suggests a means for targeting prebiotics to enrich select bifidobacterial species.
Longitudinal Characterization of Resistant
Escherichia coli
in Fecal Deposits from Cattle Fed Subtherapeutic Levels of Antimicrobials
Authors: Alexander T. W. , Reuter T. , Sharma R. , Yanke L. J. , Topp E. , McAllister T. A. 
Published: October 2009

ABSTRACT

Model fecal deposits from cattle fed or not fed antimicrobial growth promoters were examined over 175 days in the field for growth and persistence of total
Escherichia coli
and numbers and proportions of ampicillin-resistant (Amp
r
) and tetracycline-resistant (Tet
r
)
E. coli
. In addition, genotypic diversity and the frequency of genetic determinants encoded by Amp
r
and Tet
r
E. coli
were investigated. Cattle were fed diets containing chlortetracycline (44 ppm; A44 treatment group), chlortetracycline plus sulfamethazine (both at 44 ppm; AS700 treatment group), or no antibiotics (control). Fecal deposits were sampled 12 times over 175 days. Numbers of Tet
r
E. coli
in A44 and AS700 deposits were higher (
P
< 0.001) than those of controls and represented up to 35.6% and 20.2% of total
E. coli
, respectively. A time-by-treatment interaction (
P
< 0.001) was observed for the numbers of Tet
r
and Amp
r
E. coli.
Except for Amp
r
E. coli
in control deposits, all
E. coli
numbers increased (
P
< 0.001) in deposits up to day 56. Even after 175 days, high Tet
r
E. coli
numbers were detected in A44 and AS700 deposits [5.9 log
10
CFU (g dry matter)
−
1
and 5.4 log
10
CFU (g dry matter)
−
1
, respectively].
E. coli
genotypes, as determined by pulsed-field gel electrophoresis, were diverse and were influenced by the antimicrobial growth promoter and the sampling time. Of the determinants screened,
bla
TEM1
,
tetA
,
tetB
,
tetC
,
sul1
, and
sul2
were frequently detected. Occurrence of determinants was influenced by the feeding of antimicrobials. Fecal deposits remain a source of resistant
E. coli
even after a considerable period of environmental exposure.
Distribution and Diversity of Archaeal and Bacterial Ammonia Oxidizers in Salt Marsh Sediments
Authors: Moin Nicole S. , Nelson Katelyn A. , Bush Alexander , Bernhard Anne E. 
Published: October 2009

ABSTRACT

Diversity and abundance of ammonia-oxidizing
Betaproteobacteria
(β-AOB) and archaea (AOA) were investigated in a New England salt marsh at sites dominated by short or tall
Spartina alterniflora
(SAS and SAT sites, respectively) or
Spartina patens
(SP site). AOA
amoA
gene richness was higher than β-AOB
amoA
richness at SAT and SP, but AOA and β-AOB richness were similar at SAS. β-AOB
amoA
clone libraries were composed exclusively of
Nitrosospira
-like
amoA
genes. AOA
amoA
genes at SAT and SP were equally distributed between the water column/sediment and soil/sediment clades, while AOA
amoA
sequences at SAS were primarily affiliated with the water column/sediment clade. At all three site types, AOA were always more abundant than β-AOB based on quantitative PCR of
amoA
genes. At some sites, we detected 10
9
AOA
amoA
gene copies g of sediment
−1
. Ratios of AOA to β-AOB varied over 2 orders of magnitude among sites and sampling dates. Nevertheless, abundances of AOA and β-AOB
amoA
genes were highly correlated. Abundance of 16S rRNA genes affiliated with
Nitrosopumilus maritimus
,
Crenarchaeota
group I.1b, and pSL12 were positively correlated with AOA
amoA
abundance, but ratios of
amoA
to 16S rRNA genes varied among sites. We also observed a significant effect of pH on AOA abundance and a significant salinity effect on both AOA and β-ΑΟΒ abundance. Our results expand the distribution of AOA to salt marshes, and the high numbers of AOA at some sites suggest that salt marsh sediments serve as an important habitat for AOA.
Impact of an 8-Year-Old Transgenic Poplar Plantation on the Ectomycorrhizal Fungal Community
Authors: Stefani Franck O. P. , Moncalvo Jean-Marc , Séguin Armand , Bérubé Jean A. , Hamelin Richard C. 
Published: October 2009

ABSTRACT

The long-term impact of field-deployed genetically modified trees on soil mutualistic organisms is not well known. This study aimed at evaluating the impact of poplars transformed with a binary vector containing the selectable
nptII
marker and β-glucuronidase reporter genes on ectomycorrhizal (EM) fungi 8 years after field deployment. We generated 2,229 fungal internal transcribed spacer (ITS) PCR products from 1,150 EM root tips and 1,079 fungal soil clones obtained from the organic and mineral soil horizons within the rhizosphere of three control and three transformed poplars. Fifty EM fungal operational taxonomic units were identified from the 1,706 EM fungal ITS amplicons retrieved. Rarefaction curves from both the root tips and soil clones were close to saturation, indicating that most of the EM species present were recovered. Based on qualitative and/or quantitative α- and β-diversity measurements, statistical analyses did not reveal significant differences between EM fungal communities associated with transformed poplars and the untransformed controls. However, EM communities recovered from the root tips and soil cloning analyses differed significantly from each other. We found no evidence of difference in the EM fungal community structure linked to the long-term presence of the transgenic poplars studied, and we showed that coupling root tip analysis with a soil DNA cloning strategy is a complementary approach to better document EM fungal diversity.
Functional Tomographic Fluorescence Imaging of pH Microenvironments in Microbial Biofilms by Use of Silica Nanoparticle Sensors
Authors: Hidalgo Gabriela , Burns Andrew , Herz Erik , Hay Anthony G. , Houston Paul L. , Wiesner Ulrich , Lion Leonard W. 
Published: October 2009

ABSTRACT

Attached bacterial communities can generate three-dimensional (3D) physicochemical gradients that create microenvironments where local conditions are substantially different from those in the surrounding solution. Given their ubiquity in nature and their impacts on issues ranging from water quality to human health, better tools for understanding biofilms and the gradients they create are needed. Here we demonstrate the use of functional tomographic imaging via confocal fluorescence microscopy of ratiometric core-shell silica nanoparticle sensors (C dot sensors) to study the morphology and temporal evolution of pH microenvironments in axenic
Escherichia coli
PHL628 and mixed-culture wastewater biofilms. Testing of 70-, 30-, and 10-nm-diameter sensor particles reveals a critical size for homogeneous biofilm staining, with only the 10-nm-diameter particles capable of successfully generating high-resolution maps of biofilm pH and distinct local heterogeneities. Our measurements revealed pH values that ranged from 5 to >7, confirming the heterogeneity of the pH profiles within these biofilms. pH was also analyzed following glucose addition to both suspended and attached cultures. In both cases, the pH became more acidic, likely due to glucose metabolism causing the release of tricarboxylic acid cycle acids and CO
2
. These studies demonstrate that the combination of 3D functional fluorescence imaging with well-designed nanoparticle sensors provides a powerful tool for in situ characterization of chemical microenvironments in complex biofilms.
Novel Electrochemically Active Bacterium Phylogenetically Related to
Arcobacter butzleri
, Isolated from a Microbial Fuel Cell
Authors: Fedorovich Viatcheslav , Knighton Matthew C. , Pagaling Eulyn , Ward F. Bruce , Free Andrew , Goryanin Igor 
Published: October 2009

ABSTRACT

Exoelectrogenic bacteria are organisms that can transfer electrons to extracellular insoluble electron acceptors and have the potential to be used in devices such as microbial fuel cells (MFCs). Currently, exoelectrogens have been identified in the
Alpha
-,
Beta
-,
Gamma
- and
Deltaproteobacteria
, as well as in the
Firmicutes
and
Acidobacteria
. Here, we describe use of culture-independent methods to identify two members of the genus
Arcobacter
in the
Epsilon
p
roteobacteria
that are selectively enriched in an acetate-fed MFC. One of these organisms,
Arcobacter butzleri
strain ED-1, associates with the electrode and rapidly generates a strong electronegative potential as a pure culture when it is supplied with acetate. A mixed-community MFC in which ∼90% of the population is comprised of the two
Arcobacter
species generates a maximal power density of 296 mW/liter. This demonstration of exoelectrogenesis by strain ED-1 is the first time that this property has been shown for members of this genus.
Long-Term Survival of
Campylobacter jejuni
at Low Temperatures Is Dependent on Polynucleotide Phosphorylase Activity
Authors: Haddad Nabila , Burns Christopher M. , Bolla Jean Michel , Prévost Hervé , Fédérighi Michel , Drider Djamel , Cappelier Jean Michel 
Published: October 2009

ABSTRACT

Campylobacter jejuni
is a leading cause of bacterial gastroenteritis worldwide. Infection generally occurs after ingestion of contaminated poultry products, usually conserved at low temperatures. The mechanisms promoting survival of
C. jejuni
in the cold remain poorly understood despite several investigations. The present study provides insight into the survival mechanism by establishing the involvement of polynucleotide phosphorylase (PNPase), a 3′-5′ exoribonuclease with multiple biological functions in cold survival. The role of PNPase was demonstrated genetically using strains with altered
pnp
genes (which encode PNPase) created in
C. jejuni
F38011 and
C. jejuni
81-76 backgrounds. Survival assays carried out at low temperatures (4 and 10°C) revealed a difference of 3 log CFU/ml between the wild-type and the
pnp
deletion (Δ
pnp
) strains. This did not result from a general requirement for PNPase because survival rates of the strains were similar at higher growth temperatures (37 or 42°C).
trans
-Complementation with plasmid pNH04 carrying the
pnp
gene under the control of its natural promoter restored the cold survival phenotype to the
pnp
deletion strains (at 4 and 10°C) but not to the same level as the wild type. In this study we demonstrate the role of PNPase in low-temperature survival of
C. jejuni
and therefore attribute a novel biological function to PNPase directly related to human health.