bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine
Authors: Ceckova Martina , Reznicek Josef , Ptackova Zuzana , Cerveny Lukas , Müller Fabian , Kacerovsky Marian , Fromm Martin F. , Glazier Jocelyn D. , Staud Frantisek 
Published: July 2016

ABSTRACTLamivudine is one of the antiretroviral drugs of choice for the prevention of mother-to-child transmission (MTCT) in HIV-positive women. In this study, we investigated the relevance of drug efflux transporters P-glycoprotein (P-gp) (MDR1 [ABCB1]), BCRP (ABCG2), MRP2 (ABCC2), and MATE1 (SLC47A1) for the transmembrane transport and transplacental transfer of lamivudine. We employedin vitroaccumulation and transport experiments on MDCK cells overexpressing drug efflux transporters,in situ-perfused rat term placenta, and vesicular uptake in microvillous plasma membrane (MVM) vesicles isolated from human term placenta. MATE1 significantly accelerated lamivudine transport in MATE1-expressing MDCK cells, whereas no transporter-driven efflux of lamivudine was observed in MDCK-MDR1, MDCK-MRP2, and MDCK-BCRP monolayers. MATE1-mediated efflux of lamivudine appeared to be a low-affinity process (apparentKmof 4.21 mM andVmaxof 5.18 nmol/mg protein/min in MDCK-MATE1 cells). Consistent within vitrotransport studies, the transplacental clearance of lamivudine was not affected by P-gp, BCRP, or MRP2. However, lamivudine transfer across dually perfused rat placenta and the uptake of lamivudine into human placental MVM vesicles revealed pH dependency, indicating possible involvement of MATE1 in the fetal-to-maternal efflux of the drug. To conclude, placental transport of lamivudine does not seem to be affected by P-gp, MRP2, or BCRP, but a pH-dependent mechanism mediates transport of lamivudine in the fetal-to-maternal direction. We suggest that MATE1 might be, at least partly, responsible for this transport.
Molecular Epidemiology of a Vancomycin-Intermediate Heteroresistant Staphylococcus epidermidis Outbreak in a Neonatal Intensive Care Unit
Authors: Chong Jasmine , Quach Caroline , Blanchard Ana C. , Poliquin Philippe Guillaume , Golding George R. , Laferrière Céline , Lévesque Simon 
Published: July 2016

ABSTRACT

Coagulase-negative staphylococci (CoNS) have become the leading cause of bloodstream infections (BSIs) in intensive care units (ICUs), particularly in premature neonates. Vancomycin-intermediate heteroresistant CoNS (hVICoNS) have been identified as sources of BSIs worldwide, and their potential to emerge as significant pathogens in the neonatal ICU (NICU) remains uncertain. This study describes the molecular epidemiology of an outbreak of vancomycin-heteroresistant (hV)
Staphylococcus epidermidis
central-line-associated BSI (CLABSI) in a single tertiary care NICU and compares it to a second tertiary care NICU that had not been associated with an outbreak. Between November 2009 and April 2014, 119
S. epidermidis
CLABSIs were identified in two tertiary care NICUs in Quebec, Canada. Decreased vancomycin susceptibility was identified in about 88% of all collected strains using Etest methods. However, discrepancies were found according to the Etest and population analysis profiling–area under the concentration-time curve (PAP-AUC) methods used. All strains were susceptible to linezolid, and a few isolates were nonsusceptible to daptomycin. Great genetic diversity was observed within the collection, with 31 pulsed-field gel electrophoresis (PFGE) patterns identified. The outbreak strains were all determined to be heteroresistant to vancomycin and were polyclonal. The study identified two major clones, PFGE patterns E and G, which were found in both NICUs across the 5-year study period. This suggests the persistence of highly successful clones that are well adapted to the hospital environment. hV
S. epidermidis
seems more common than currently realized in the NICU, and certain hV
S. epidermidis
clones can become endemic to the NICU. The reservoirs for these clones remain unknown at this time, and identification of the reservoirs is needed to better understand the impact of hV
S. epidermidis
in the NICU and to inform infection prevention strategies. In addition, there is a need to investigate and validate hV determination protocols for different species of CoNS.
Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae
Authors: Figueira M. , Fernandes P. , Pelton S. I. 
Published: July 2016

ABSTRACT

Solithromycin (CEM-101) is a “fourth-generation” macrolide, as it has three binding site and is acid stable. The three binding sites confer activity against bacteria resistant to the older macrolides and ketolides, including multidrug-resistant
Streptococcus pneumoniae
and nontypeable
Haemophilus influenzae
(NTHi). The objective of this study was to evaluate solithromycin pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of experimental otitis media (EOM) due to strains of
S. pneumoniae
or NTHi. Plasma PK (maximum concentration of drug in serum [
C
max
] and area under the concentration-time curve from 0 to 24 h [AUC
0–24
]) and middle ear fluid (MEF) concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy. Solithromycin administered at 150 mg/kg of body weight/day resulted in
C
max
and AUC
0–24
values of 2.2 μg/ml and 27.4 μg · h/ml in plasma and 1.7 μg/ml and 28.2 μg · h/ml in extracellular MEF on day 1. By day 3,
C
max
and AUC
0–24
values had increased to 4.5 μg/ml and 54 μg · h/ml in plasma and 4.8 μg/ml and 98.6 μg · h/ml in extracellular MEF. For NTHi EOM, three isolates with MIC/minimal bactericidal concentration (MBC) ratios of 0.5/1 μg/ml (isolate BCH1), 2/2 μg/ml (isolate BMC1247C), and 4/4 μg/ml (isolate BMC1213C) were selected. The MEF of >85% of animals infected with BCH1 and BMC1247C was sterilized. For NTHi BMC1213, >85% of MEF cultures remained positive. For
S. pneumoniae
EOM, 3 isolates with MIC/MBC ratios of 0.06/0.125 μg/ml (
S. pneumoniae
331), 0.125/1 μg/ml (
S. pneumoniae
CP-645 [MLS
B
phenotype]), and 0.5/2 μg/ml (CP-712 [
mefA
subclass
mefA
resistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected with
S. pneumoniae
331 and
S. pneumoniae
CP-645. ME infection persisted in 60% of animals infected with CP-712. In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with an MIC of ≤2 μg/ml and 100% of ME infected with
S. pneumoniae
with an MIC of ≤0.125 μg/ml.
Impact of Time to Appropriate Therapy on Mortality in Patients with Vancomycin-Intermediate Staphylococcus aureus Infection
Authors: Burnham Jason P. , Burnham Carey-Ann D. , Warren David K. , Kollef Marin H. 
Published: July 2016

ABSTRACT

Despite the increasing incidence of vancomycin-intermediate
Staphylococcus aureus
(VISA) infections, few studies have examined the impact of delay in receipt of appropriate antimicrobial therapy on outcomes in VISA patients. We examined the effects of timing of appropriate antimicrobial therapy in a cohort of patients with sterile-site methicillin-resistant
S. aureus
(MRSA) and VISA infections. In this single-center, retrospective cohort study, we identified all patients with MRSA or VISA sterile-site infections from June 2009 to February 2015. Clinical outcomes were compared according to MRSA/VISA classification, demographics, comorbidities, and antimicrobial treatment. Thirty-day all-cause mortality was modeled with Kaplan-Meier curves. Multivariate logistic regression analysis (MVLRA) was used to determine odds ratios for mortality. We identified 354 patients with MRSA (
n
= 267) or VISA (
n
= 87) sterile-site infection. Fifty-five patients (15.5%) were nonsurvivors. Factors associated with mortality in MVLRA included pneumonia, unknown source of infection, acute physiology and chronic health evaluation (APACHE) II score, solid-organ malignancy, and admission from skilled care facilities. Time to appropriate antimicrobial therapy was not significantly associated with outcome. Presence of a VISA infection compared to that of a non-VISA
S. aureus
infection did not result in excess mortality. Linezolid use was a risk for mortality in patients with APACHE II scores of ≥14. Our results suggest that empirical vancomycin use in patients with VISA infections does not result in excess mortality. Future studies should (i) include larger numbers of patients with VISA infections to confirm the findings presented here and (ii) determine the optimal antibiotic therapy for critically ill patients with MRSA and VISA infections.
mcr-1.2
, a New
mcr
Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512
Authors: Di Pilato Vincenzo , Arena Fabio , Tascini Carlo , Cannatelli Antonio , Henrici De Angelis Lucia , Fortunato Simona , Giani Tommaso , Menichetti Francesco , Rossolini Gian Maria 
Published: July 2016

ABSTRACT

A novel
mcr
variant, named
mcr-1.2
, encoding a Gln
3
-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512
Klebsiella pneumoniae
isolate collected in Italy from a surveillance rectal swab from a leukemic child. The
mcr-1.2
gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of
mcr-1
-bearing plasmids previously found in
Escherichia coli
and
K. pneumoniae
strains from geographically distant sites (Estonia, China, and South Africa).
Novel
acsF
Gene Primers Revealed a Diverse Phototrophic Bacterial Population, Including Gemmatimonadetes, in Lake Taihu (China)
Authors: Huang Yili , Zeng Yanhua , Lu Hang , Feng Hao , Zeng Yonghui , Koblížek Michal 
Published: July 2016

ABSTRACT

Anoxygenic phototrophs represent an environmentally important and phylogenetically diverse group of organisms. They harvest light using bacteriochlorophyll-containing reaction centers. Recently, a novel phototrophic bacterium,
Gemmatimonas phototrophica
, belonging to a rarely studied phylum,
Gemmatimonadetes
, was isolated from a freshwater lake in the Gobi Desert. To obtain more information about the environmental distribution of phototrophic
Gemmatimonadetes
, we collected microbial samples from the water column, upper sediment, and deeper anoxic sediment of Lake Taihu, China. MiSeq sequencing of the 16S rRNA,
pufM
, and
bchY
genes was carried out to assess the diversity of local phototrophic communities. In addition, we designed new degenerate primers of aerobic cyclase gene
acsF
, which serves as a convenient marker for both phototrophic
Gemmatimonadetes
and phototrophic
Proteobacteria
. Our results showed that most of the phototrophic species in Lake Taihu belong to
Alpha
- and
Betaproteobacteria
. Sequences of green sulfur and green nonsulfur bacteria (phototrophic
Chlorobi
and
Chloroflexi
, respectively) were found in the sediment. Using the newly designed primers, we identified a diverse community of phototrophic
Gemmatimonadetes
forming 30 operational taxonomic units. These species represented 10.5 and 17.3% of the
acsF
reads in the upper semiaerobic sediment and anoxic sediment, whereas their abundance in the water column was <1%.

IMPORTANCE
Photosynthesis is one of the most fundamental biological processes on Earth. Recently, the presence of photosynthetic reaction centers has been reported from a rarely studied bacterial phylum,
Gemmatimonadetes
, but almost nothing is known about the diversity and environmental distribution of these organisms. The newly designed
acsF
primers were used to identify phototrophic
Gemmatimonadetes
from planktonic and sediment samples collected in Lake Taihu, China. The
Gemmatimonadetes
sequences were found mostly in the upper sediments, documenting the preference of
Gemmatimonadetes
for semiaerobic conditions. Our results also show that the phototrophic
Gemmatimonadetes
present in Lake Taihu were relatively diverse, encompassing 30 operational taxonomic units.
North-Seeking Magnetotactic Gammaproteobacteria in the Southern Hemisphere
Authors: Leão Pedro , Teixeira Lia C. R. S. , Cypriano Jefferson , Farina Marcos , Abreu Fernanda , Bazylinski Dennis A. , Lins Ulysses 
Published: July 2016

ABSTRACT

Magnetotactic bacteria (MTB) comprise a phylogenetically diverse group of prokaryotes capable of orienting and navigating along magnetic field lines. Under oxic conditions, MTB in natural environments in the Northern Hemisphere generally display north-seeking (NS) polarity, swimming parallel to the Earth's magnetic field lines, while those in the Southern Hemisphere generally swim antiparallel to magnetic field lines (south-seeking [SS] polarity). Here, we report a population of an uncultured, monotrichously flagellated, and vibrioid MTB collected from a brackish lagoon in Brazil in the Southern Hemisphere that consistently exhibits NS polarity. Cells of this organism were mainly located below the oxic-anoxic interface (OAI), suggesting it is capable of some type of anaerobic metabolism. Magnetosome crystalline habit and composition were consistent with elongated prismatic magnetite (Fe
3
O
4
) particles. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that this organism belongs to a distinct clade of the
Gammaproteobacteria
class. The presence of NS MTB in the Southern Hemisphere and the previously reported finding of SS MTB in the Northern Hemisphere reinforce the idea that magnetotaxis is more complex than we currently understand and may be modulated by factors other than O
2
concentration and redox gradients in sediments and water columns.

IMPORTANCE
Magnetotaxis is a navigational mechanism used by magnetotactic bacteria to move along geomagnetic field lines and find an optimal position in chemically stratified sediments. For that, magnetotactic bacteria swim parallel to the geomagnetic field lines under oxic conditions in the Northern Hemisphere, whereas those in the Southern Hemisphere swim antiparallel to magnetic field lines. A population of uncultured vibrioid magnetotactic bacteria was discovered in a brackish lagoon in the Southern Hemisphere that consistently swim northward, i.e., the opposite of the overwhelming majority of other Southern Hemisphere magnetotactic bacteria. This finding supports the idea that magnetotaxis is more complex than previously thought.
Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection
Authors: Zafar M. Ammar , Kono Masamitsu , Wang Yang , Zangari Tonia , Weiser Jeffrey N. 
Published: July 2016

ABSTRACTOne of the least understood aspects of the bacteriumStreptococcus pneumoniae(pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized “index” pups to uncolonized “contact” pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection.
Evidence for Escherichia coli Diguanylate Cyclase DgcZ Interlinking Surface Sensing and Adhesion via Multiple Regulatory Routes
Authors: Lacanna Egidio , Bigosch Colette , Kaever Volkhard , Boehm Alex , Becker Anke 
Published: July 2016

ABSTRACT

DgcZ is the main cyclic dimeric GMP (c-di-GMP)-producing diguanylate cyclase (DGC) controlling biosynthesis of the exopolysaccharide poly-β-1,6-
N
-acetylglucosamine (poly-GlcNAc or PGA), which is essential for surface attachment of
Escherichia coli
. Although the complex regulation of DgcZ has previously been investigated, its primary role and the physiological conditions under which the protein is active are not fully understood. Transcription of
dgcZ
is regulated by the two-component system CpxAR activated by the lipoprotein NlpE in response to surface sensing. Here, we show that the negative effect of a
cpxR
mutation and the positive effect of
nlpE
overexpression on biofilm formation both depend on DgcZ. Coimmunoprecipitation data suggest several potential interaction partners of DgcZ. Interaction with FrdB, a subunit of the fumarate reductase complex (FRD) involved in anaerobic respiration and in control of flagellum assembly, was further supported by a bacterial-two-hybrid assay. Furthermore, the FRD complex was required for the increase in DgcZ-mediated biofilm formation upon induction of oxidative stress by addition of paraquat. A DgcZ-mVENUS fusion protein was found to localize at one bacterial cell pole in response to alkaline pH and carbon starvation. Based on our data and previous knowledge, an integrative role of DgcZ in regulation of surface attachment is proposed. We speculate that both DgcZ-stimulated PGA biosynthesis and interaction of DgcZ with the FRD complex contribute to impeding bacterial escape from the surface.

IMPORTANCE
Bacterial cells can grow by clonal expansion to surface-associated biofilms that are ubiquitous in the environment but also constitute a pervasive problem related to bacterial infections. Cyclic dimeric GMP (c-di-GMP) is a widespread bacterial second messenger involved in regulation of motility and biofilm formation, and plays a primary role in bacterial surface attachment.
E. coli
possesses a plethora of c-di-GMP-producing diguanylate cyclases, including DgcZ. Our study expands the knowledge on the role of DgcZ in regulation of surface attachment and suggests that it interconnects surface sensing and adhesion via multiple routes.
Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake
Authors: Sritharan Manjula 
Published: July 2016

ABSTRACT

Mycobacterium tuberculosis
requires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe
3+
-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival of
M. tuberculosis
, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrophages. But as excess iron is toxic due to its catalytic role in the generation of free radicals, regulation of iron uptake is necessary to maintain optimal levels of intracellular iron. The focus of this review is to present a comprehensive overview of iron homeostasis in
M. tuberculosis
that is discussed in the context of mycobactin biosynthesis, transport of iron across the mycobacterial cell envelope, and storage of excess iron. The clinical significance of the serum iron status and the expression of the iron-regulated protein HupB in tuberculosis (TB) patients is presented here, highlighting the potential of HupB as a marker, notably in extrapulmonary TB cases.
Dynamic weakening and amorphization in serpentinite during laboratory earthquakes
Authors: Brantut Nicolas , Passelègue François X. , Deldicque Damien , Rouzaud Jean-Noël , Schubnel Alexandre 
Published: July 2016

Abstract
The mechanical properties of serpentinites are key factors in our understanding of the dynamics of earthquake ruptures in subduction zones, especially intermediate-depth earthquakes. Here, we performed shear rupture experiments on natural antigorite serpentinite, which showed that friction reaches near-zero values during spontaneous dynamic rupture propagation. Rapid coseismic slip (&gt;1 m/s), although it occurs over short distances (&lt;1 mm), induces significant overheating of microscale asperities along the sliding surface, sufficient to produce surface amorphization and likely some melting. Antigorite dehydration occurs in the fault walls, which leaves a partially amorphized material. The water generated potentially contributes to the production of a low-viscosity pressurized melt, explaining the near-zero dynamic friction levels observed in some events. The rapid and dramatic dynamic weakening in serpentinite might be a key process facilitating the propagation of earthquakes at intermediate depths in subduction zones.
Electroacupuncture Improves Cognitive Deficits and Activates Ppar-γ in a Rat Model of Alzheimer's Disease
Authors: Zhang Min , Xv Gui-Hua , Wang Wei-Xin , Meng Di-Juan , Ji Yan 
Published: July 2016

Background Alzheimer's disease (AD) is an age-associated neurodegenerative disorder that is associated with a progressive impairment of cognition. Acupuncture has protective effects, although the molecular mechanisms are largely unknown. The activation of peroxisome proliferator activated receptor γ (PPAR-γ) has an impact on the pathogenesis of AD. Objective To test the hypothesis that electroacupuncture (EA) confers therapeutic benefits through activation of PPAR-γ in a rat model of AD. Methods 80 male Sprague-Dawley rats were randomly divided into four groups (n=20 each): Control (healthy control group), Sham (sham-operated group), AD (untreated AD model group), and AD+EA (AD model group treated with EA). The AD model was induced in the latter two groups by injection of amyloid-β (Aβ)1-40 into the hippocampal CA1 area bilaterally. EA was administered at GV20 and BL23 six times per week for 4 weeks. The rats’ behaviour was examined using the Morris water maze test, and protein expression of Aβ, hyperphosphorylated tau protein (p-Tau), PPAR-γ, and hyperphosphorylated p38 mitogen activated protein kinase (p38MAPK) in the hippocampal CA1 region was examined by immunohistochemistry and Western blotting. Results EA significantly improved cognitive deficits and reduced Aβ and p-Tau Ser404 protein concentrations in the hippocampal CA1 region. AD decreased PPAR-γ and increased p-p38MAPK, while EA significantly upregulated PPAR-γ expression and significantly downregulated p-p38MAPK expression. Conclusions Acupuncture at GV20 and BL23 might have a beneficial effect on rats with AD via activation of PPAR-γ and inhibition of p-p38MAPK expression.