bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a P1-Like Bacteriophage Carrying an SHV-2 Extended-Spectrum β-Lactamase from an Escherichia coli Strain
Authors: Billard-Pomares Typhaine , Fouteau Stéphanie , Jacquet Marie Elise , Roche David , Barbe Valérie , Castellanos Miguel , Bouet Jean Yves , Cruveiller Stéphane , Médigue Claudine , Blanco Jorge , Clermont Olivier , Denamur Erick , Branger Catherine 
Published: August 2014

ABSTRACT

P1 bacteriophages lysogenize bacteria as independent plasmid-like elements. We describe here a P1-like bacteriophage, RCS47, carrying a
bla
SHV-2
gene, isolated from a clinical strain of
Escherichia coli
from phylogroup B1, and we report the prevalence of P1-like prophages in natural
E. coli
isolates. We found that 70% of the sequence of RCS47, a 115-kb circular molecule, was common to the reference P1 bacteriophage under GenBank accession no.
AF234172.1
, with the shared sequences being 99% identical. RCS47 had acquired two main foreign DNA fragments: a 9,636-bp fragment mobilized by two IS
26
elements containing a
bla
SHV-2
gene, and an 8,544-bp fragment mobilized by two IS
5
elements containing an operon encoding a dimethyl sulfoxide reductase. The reference P1 prophage plasmid replication gene belonged to the IncY incompatibility group, whereas that of RCS47 was from an unknown group. The lytic capacity of RCS47 and
bla
SHV-2
gene transduction, through the lysogenization of RCS47 in the recipient
E. coli
strains, were not demonstrated. The prevalence of P1-like prophages in various animal and human
E. coli
strain collections, as determined by the PCR detection of
repL
, the lytic replication gene, was 12.6%. No differences in the prevalences of these prophages were found between extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing strains (
P
= 0.69), but this prevalence was lower in phylogroup B2 than in the other phylogroups (
P
= 0.008), suggesting epistatic interactions between P1 family phages and the genetic background of
E. coli
strains. P1-like phages are part of the mobile elements that carry antibiotic resistance. The high prevalence of P1-like prophages suggests their role may be underestimated.
Novel Insights into the Mechanism of Inhibition of MmpL3, a Target of Multiple Pharmacophores in Mycobacterium tuberculosis
Authors: Li Wei , Upadhyay Ashutosh , Fontes Fabio L. , North E. Jeffrey , Wang Yuehong , Crans Debbie C. , Grzegorzewicz Anna E. , Jones Victoria , Franzblau Scott G. , Lee Richard E. , Crick Dean C. , Jackson Mary 
Published: August 2014

ABSTRACT

MmpL3, a resistance-nodulation-division (RND) superfamily transporter, has been implicated in the formation of the outer membrane of
Mycobacterium tuberculosis
; specifically, MmpL3 is required for the export of mycolic acids in the form of trehalose monomycolates (TMM) to the periplasmic space or outer membrane of
M. tuberculosis
. Recently, seven series of inhibitors identified by whole-cell screening against
M. tuberculosis
, including the antituberculosis drug candidate SQ109, were shown to abolish MmpL3-mediated TMM export. However, this mode of action was brought into question by the broad-spectrum activities of some of these inhibitors against a variety of bacterial and fungal pathogens that do not synthesize mycolic acids. This observation, coupled with the ability of three of these classes of inhibitors to kill nonreplicating
M. tuberculosis
bacilli, led us to investigate alternative mechanisms of action. Our results indicate that the inhibitory effects of adamantyl ureas, indolecarboxamides, tetrahydropyrazolopyrimidines, and the 1,5-diarylpyrrole BM212 on the transport activity of MmpL3 in actively replicating
M. tuberculosis
bacilli are, like that of SQ109, most likely due to their ability to dissipate the transmembrane electrochemical proton gradient. In addition to providing novel insights into the modes of action of compounds reported to inhibit MmpL3, our results provide the first explanation for the large number of pharmacophores that apparently target this essential inner membrane transporter.
Distinct Roles of Major Peptidoglycan Recycling Enzymes in β-Lactamase Production in Shewanella oneidensis
Authors: Yin Jianhua , Mao Yinting , Ju Lili , Jin Miao , Sun Yiyang , Jin Shouguang , Gao Haichun 
Published: August 2014

ABSTRACT

β-Lactam antibiotics were the earliest discovered and are the most widely used group of antibiotics that work by inactivating penicillin-binding proteins to inhibit peptidoglycan biosynthesis. As one of the most efficient defense strategies, many bacteria produce β-lactam-degrading enzymes, β-lactamases, whose biochemical functions and regulation have been extensively studied. A signal transduction pathway for β-lactamase induction by β-lactam antibiotics, consisting of the major peptidoglycan recycling enzymes and the LysR-type transcriptional regulator, AmpR, has been recently unveiled in some bacteria. Because inactivation of some of these proteins, especially the permease AmpG and the β-hexosaminidase NagZ, results in substantially elevated susceptibility to the antibiotics, these have been recognized as potential therapeutic targets. Here, we show a contrasting scenario in
Shewanella oneidensis
, in which the homologue of AmpR is absent. Loss of AmpG or NagZ enhances β-lactam resistance drastically, whereas other identified major peptidoglycan recycling enzymes are dispensable. Moreover, our data indicate that there exists a parallel signal transduction pathway for β-lactamase induction, which is independent of either AmpG or NagZ.
In Vivo
Efficacy of Apramycin in Murine Infection Models
Authors: Meyer Martin , Freihofer Pietro , Scherman Michael , Teague Joanne , Lenaerts Anne , Böttger Erik C. 
Published: August 2014

ABSTRACT

Apramycin is a unique aminoglycoside with a dissociation of antibacterial activity and ototoxicity. We assessed the antibacterial efficacy of apramycin in two murine models of infection,
Mycobacterium tuberculosis
aerosol infection and
Staphylococcus aureus
septicemia. In both infection models, the efficacy of apramycin was comparable to that of amikacin. These results suggest that apramycin has the potential to become a clinically useful agent against drug-resistant pathogens and support further development of this promising unique aminoglycoside.
Identification and Characterization of Linezolid-Resistantcfr-Positive Staphylococcus aureus USA300 Isolates from a New York City Medical Center
Authors: Locke Jeffrey B. , Zuill Douglas E. , Scharn Caitlyn R. , Deane Jennifer , Sahm Daniel F. , Goering Richard V. , Jenkins Stephen G. , Shaw Karen J. 
Published: August 2014

ABSTRACTThecfrgene was identified in three linezolid-resistant USA300 methicillin-resistantStaphylococcus aureus(MRSA) isolates collected over a 3-day period at a New York City medical center in 2011 as part of a routine surveillance program. Each isolate possessed a plasmid containing a pSCFS3-likecfrgene environment. Transformation of thecfr-bearing plasmids into theS. aureusATCC 29213 background recapitulated the expected Cfr antibiogram, including resistance to linezolid, tiamulin, clindamycin, and florfenicol and susceptibility to tedizolid.
Ceftaroline-Fosamil Efficacy against Methicillin-Resistant Staphylococcus aureus in a Rabbit Prosthetic Joint Infection Model
Authors: Gatin Laure , Saleh-Mghir Azzam , Tasse Jason , Ghout Idir , Laurent Frédéric , Crémieux Anne-Claude 
Published: August 2014

ABSTRACT

Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstrates
in vitro
bactericidal activity against methicillin-resistant
Staphylococcus aureus
(MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, its
in vivo
efficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 × 10
7
MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although the
in vivo
mean log
10
CFU/g of CPT-treated (3.0 ± 0.9,
n
= 12) and VAN-treated (3.5 ± 1.1,
n
= 12) crushed bones was significantly lower than those of controls (5.6 ± 1.1,
n
= 14) (
P
< 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log
10
CFU/g values for the antibiotics in combination with RIF were 1.9 ± 0.5 (12/14 were sterile) for CPT-F and 1.9 ± 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs.
Molecular Characterization of Streptococcus agalactiae Isolates Harboring Small
erm
(T)-Carrying Plasmids
Authors: Compain Fabrice , Hays Constantin , Touak Gérald , Dmytruk Nicolas , Trieu-Cuot Patrick , Joubrel Caroline , Poyart Claire 
Published: August 2014

ABSTRACT

Among 1,827 group B
Streptococcus
(GBS) strains collected between 2006 and 2013 by the French National Reference Center for Streptococci, 490 (26.8%) strains were erythromycin resistant. The
erm
(T) resistance gene was found in six strains belonging to capsular polysaccharides Ia, III, and V and was carried by the same mobilizable plasmid, which could be efficiently transferred by mobilization to GBS and
Enterococcus faecalis
recipients, thus promoting a broad dissemination of
erm
(T).
Association and Virulence Gene Expression Vary among Serotype III Group B Streptococcus Isolates following Exposure to Decidual and Lung Epithelial Cells
Authors: Korir Michelle L. , Knupp David , LeMerise Kathryn , Boldenow Erica , Loch-Caruso Rita , Aronoff David M. , Manning Shannon D. 
Published: August 2014

ABSTRACT

Group B
Streptococcus
(GBS) causes severe disease in neonates, the elderly, and immunocompromised individuals. GBS species are highly diverse and can be classified by serotype and multilocus sequence typing. Sequence type 17 (ST-17) strains cause invasive neonatal disease more frequently than strains of other STs. Attachment and invasion of host cells are key steps in GBS pathogenesis. We investigated whether four serotype III strains representing ST-17 (two strains), ST-19, and ST-23 differ in their abilities to attach to and invade both decidual cells and lung epithelial cells. Virulence gene expression following host cell association and exposure to amnion cells was also tested. The ST-17 strains differed in their abilities to attach to and invade decidual cells, whereas there were no differences with lung epithelial cells. The ST-19 and ST-23 strains, however, attached to and invaded decidual cells less than both ST-17 strains. Although the ST-23 strain attached to lung epithelial cells better than ST-17 and -19 strains, none of the strains effectively invaded the lung epithelial cells. Notably, the association with host cells resulted in the differential expression of several virulence genes relative to basal expression levels. Similar expression patterns of some genes were observed regardless of cell type used. Collectively, these results show that GBS strains differ in their abilities to attach to distinct host cell types and express key virulence genes that are relevant to the disease process. Enhancing our understanding of pathogenic mechanisms could aid in the identification of novel therapeutic targets or vaccine candidates that could potentially decrease morbidity and mortality associated with neonatal infections.
HilD Induces Expression of Salmonella Pathogenicity Island 2 Genes by Displacing the Global Negative Regulator H-NS from
ssrAB
Authors: Martínez Luary C. , Banda María M. , Fernández-Mora Marcos , Santana Francisco J. , Bustamante Víctor H. 
Published: August 2014

ABSTRACT

Salmonella
pathogenicity islands 1 and 2 (SPI-1 and SPI-2) have essential roles in the pathogenesis of
Salmonella enterica
. Previously, we reported transcriptional cross talk between SPI-1 and SPI-2 when the SPI-1 regulator HilD induces expression of the SsrA/B two-component system, the central positive regulator of SPI-2, during the growth of
Salmonella
to late stationary phase in LB rich medium. Here, we further define the mechanism of the HilD-mediated expression of
ssrAB
. Expression analysis of
cat
transcriptional fusions containing different regions of
ssrAB
revealed the presence of negative regulatory sequences located downstream of the
ssrAB
promoter. In the absence of these negative
cis
elements,
ssrAB
was expressed in a HilD-independent manner and was no longer repressed by the global regulator H-NS. Consistently, when the activity of H-NS was inactivated, the expression of
ssrAB
also became independent of HilD. Furthermore, electrophoretic mobility shift assays showed that both HilD and H-NS bind to the
ssrAB
region containing the repressing sequences. Moreover, HilD was able to displace H-NS bound to this region, whereas H-NS did not displace HilD. Our results support a model indicating that HilD displaces H-NS from a region downstream of the promoter of
ssrAB
by binding to sites overlapping or close to those sites bound by H-NS, which leads to the expression of
ssrAB
. Although the role of HilD as an antagonist of H-NS has been reported before for other genes, this is the first study showing that HilD is able to effectively displace H-NS from the promoter of one of its target genes.
Discovery of Novel Peptides Regulating Competence Development in Streptococcus mutans
Authors: Ahn Sang-Joon , Kaspar Justin , Kim Jeong Nam , Seaton Kinda , Burne Robert A. 
Published: August 2014

ABSTRACT

A MarR-like transcriptional repressor (RcrR) and two predicted ABC efflux pumps (RcrPQ) encoded by a single operon were recently shown to be dominant regulators of stress tolerance and development of genetic competence in the oral pathogen
Streptococcus mutans
. Here, we focused on polar (Δ
rcrR
-P) and nonpolar (Δ
rcrR
-NP)
rcrR
mutants, which are hyper- and nontransformable, respectively, to dissect the mechanisms by which these mutations impact competence. We discovered two open reading frames (ORFs) in the 3′ end of the
rcrQ
gene that encode peptides of 27 and 42 amino acids (aa) which are also dramatically upregulated in the Δ
rcrR
-NP strain. Deletion of, or start codon mutations in, the ORFs for the peptides in the Δ
rcrR
-NP background restored competence and sensitivity to competence-stimulating peptide (CSP) to levels seen in the Δ
rcrR
-P strain. Overexpression of the peptides adversely affected competence development. Importantly, overexpression of mutant derivatives of the ABC exporters that lacked the peptides also resulted in impaired competence. FLAG-tagged versions of the peptides could be detected in
S. mutans
, and FLAG tagging of the peptides impaired their function. The competence phenotypes associated with the various mutations, and with overexpression of the peptides and ABC transporters, were correlated with the levels of ComX protein in cells. Collectively, these studies revealed multiple novel mechanisms for regulation of competence development by the components of the
rcrRPQ
operon. Given their intimate role in competence and stress tolerance, the
rcrRPQ
-encoded peptides may prove to be useful targets for therapeutics to diminish the virulence of
S. mutans
.
Bubble formation occurs in insulin pumps in response to changes in ambient temperature and atmospheric pressure but not as a result of vibration
Authors: Lopez Prudence E , King Bruce R , Goss Peter W , Chockalingam Ganesh 
Published: August 2014

IntroductionBubble formation in insulin pump giving sets is a common problem. We studied change in temperature, change in atmospheric pressure, and vibration as potential mechanisms of bubble formation.Methods5 Animas 2020 pumps with 2 mL cartridges and Inset II infusion systems, 5 Medtronic Paradigm pumps with 1.8 mL cartridge and Quickset and 3 Roche Accu-chek pumps with 3.15 mL cartridges were used. Temperature study: insulin pumps were exposed to a temperature change from 4°C to 37°C. Pressure study: insulin pumps were taken to an altitude of 300 m. Vibration study: insulin pumps were vigorously shaken. All were observed for bubble formation.ResultsBubble formation was observed with changes in temperature and atmospheric pressure. Bubble formation did not occur with vibration.DiscussionChanges in insulin temperature and atmospheric pressure are common and may result in bubble formation. Vibration may distribute bubbles but does not cause bubble formation.
Patients as teachers: a randomised controlled trial on the use of personal stories of harm to raise awareness of patient safety for doctors in training
Authors: Jha Vikram , Buckley Hannah , Gabe Rhian , Kanaan Mona , Lawton Rebecca , Melville Colin , Quinton Naomi , Symons Jools , Thompson Zoe , Watt Ian , Wright John 
Published: August 2014

BackgroundPatient safety training often provides learners with a health professional's perspective rather than the patient's. Personal narratives of health-related harm allow patients to share their stories with health professionals to influence clinical behaviour by rousing emotions and improving attitudes to safety.AimThis study measured the impact of patient narratives used to train junior doctors in patient safety.MethodsAn open, multi-centre, two-arm, parallel design randomised controlled trial was conducted in the North Yorkshire East Coast Foundation School (NYECFS). The intervention consisted of 1-h-long patient narratives followed by discussion. The control arm received conventional faculty-delivered teaching. The Attitude to Patient Safety Questionnaire (APSQ) and the Positive and Negative Affect Schedule (PANAS) were used to measure the impact of the intervention.Results142 trainees received the intervention; 141 the control teaching. There was no evidence of a difference in post-intervention APSQ scores between the groups. There was a statistically significant difference in the underlying distribution of both post PA (positive affect) and post NA (negative affect) scores between the groups on the PANAS (p<0.001) with indications of both higher PA and NA scores in the intervention group.ConclusionsInvolving patients with experiences of safety incidents in training has an ideological appeal and seems an obvious choice in designing safety interventions. On the basis of our primary outcome measure, we were unable to demonstrate effectiveness of the intervention in changing general attitudes to safety compared to control. While the intervention may impact on emotional engagement and learning about communication, we remain uncertain whether this will translate into improved behaviours in the clinical context or indeed if there are any negative effects.Trial registration numberGrant reference no. RP-PG-0108-10049.
Perceived neighbourhood social cohesion and myocardial infarction
Authors: Kim Eric S , Hawes Armani M , Smith Jacqui 
Published: August 2014

BackgroundThe main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviours. Although important, emphasis on individuals has diverted focus and responsibility away from neighbourhood characteristics, which also strongly influence people's behaviours. Although a growing body of research has repeatedly demonstrated strong associations between neighbourhood characteristics and cardiovascular health, it has typically focused on negative neighbourhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighbourhood characteristics, such as perceived neighbourhood social cohesion.MethodsUsing multiple logistic regression models, we tested whether higher perceived neighbourhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Study—a nationally representative panel study of American adults over the age of 50—were used to analyse 5276 participants with no history of heart disease. Respondents were tracked for 4 years and analyses adjusted for relevant sociodemographic, behavioural, biological and psychosocial factors.ResultsIn a model that adjusted for age, gender, race, marital status, education and total wealth, each SD increase in perceived neighbourhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR=0.78, 95% CI 0.63 to 0.94. The association between perceived neighbourhood social cohesion and myocardial infarction remained even after adjusting for behavioural, biological and psychosocial covariates.ConclusionsHigher perceived neighbourhood social cohesion may have a protective effect against myocardial infarction.
PREDICTING FINANCIAL FAILURE OF THE TURKISH BANKS
Authors: DOĞANAY M. METE , CEYLAN NILDAĞ BAŞAK , AKTAŞ RAMAZAN 
Published: August 2014

Banks are the most important financial institutions in Turkey because other financial institutions are not developed efficiently yet. Turkish banks experienced financial difficulties and a substantial amount of banks failed in the past. This event urged the government to initiate measures to prevent banks from getting into financial difficulties. As a result of these measures, Turkish banking system currently seems to be very attractive for the foreign investors willing to invest in this sector. One of the main concerns of the foreign investors is a possibility of a new banking crisis although it is very remote at this time. The purpose of this study is to develop early warning systems predicting the financial failure at least three years ahead of financial failure date. A number of multivariate statistical models such as multiple regression, discriminant analysis, logit, probit are used. We found that the most appropriate model is logit. The significant variables obtained from the models explain very well the causes of the bank failures. Our models can be used to assist interested parties to predict the probability of financial failure of Turkish banks.
ACVR1 Mutations in DIPG: Lessons Learned from FOP
Authors: Taylor Kathryn R. , Vinci Maria , Bullock Alex N. , Jones Chris 
Published: August 2014

Abstract
Whole-genome sequencing studies have recently identified a quarter of cases of the rare childhood brainstem tumor diffuse intrinsic pontine glioma to harbor somatic mutations in ACVR1. This gene encodes the type I bone morphogenic protein receptor ALK2, with the residues affected identical to those that, when mutated in the germline, give rise to the congenital malformation syndrome fibrodysplasia ossificans progressiva (FOP), resulting in the transformation of soft tissue into bone. This unexpected link points toward the importance of developmental biology processes in tumorigenesis and provides an extensive experience in mechanistic understanding and drug development hard-won by FOP researchers to pediatric neurooncology. Here, we review the literature in both fields and identify potential areas for collaboration and rapid advancement for patients of both diseases. Cancer Res; 74(17); 4565–70. ©2014 AACR.