bluuebunny/crossref_metadata_2025_split huggingface dataset:
bla
CTX-M-1/9/1
Hybrid Genes May Have Been Generated from
bla
CTX-M-15
on an IncI2 Plasmid
Authors: Liu Lanping , He Dandan , Lv Luchao , Liu Wuling , Chen Xiaojie , Zeng Zhenling , Partridge Sally R. , Liu Jian-Hua 
Published: May 2015

ABSTRACT

Three hybrid CTX-M β-lactamases, CTX-M-64, CTX-M-123, and CTX-M-132, with N and C termini matching CTX-M-1 group enzymes and centers matching CTX-M-9 group enzymes, have been identified. The hybrid gene sequences suggested recombination between
bla
CTX-M-15
and
bla
CTX-M-14
, the two most common
bla
CTX-M
variants worldwide. However,
bla
CTX-M-64
and
bla
CTX-M-123
are found in an IS
Ecp1-bla
CTX-M
transposition unit with a 45-bp “spacer,” rather than the 48 bp usually associated with
bla
CTX-M-15
, and 112 bp of IncA/C plasmid backbone. This is closer to the context of
bla
CTX-M-55
, which has one nucleotide difference from
bla
CTX-M-15
, on IncI2 plasmid pHN1122-1. Here, we characterized an IncI2 plasmid carrying
bla
CTX-M-15
with a 45-bp spacer (pHNY2-1) by complete sequencing and also sequenced IncI2 plasmids carrying
bla
CTX-M-64
(pHNAH46-1) or
bla
CTX-M-132
(pHNLDH19) and an IncI1 plasmid carrying
bla
CTX-M-123
(pHNAH4-1). pHNY2-1 has the same IS
Ecp1-bla
CTX-M
-IncA/C insertion as pHN1122-1, pHNAH46-1, and pHNLDH19, and all four plasmid backbones are almost identical. pHNAH4-1 (IncI1 sequence type 108 [ST108]) carries a transposition unit that includes a 2,720-bp fragment of the IncI2 backbone, suggesting IS
Ecp1
-mediated transfer of
bla
CTX-M
-IncA/C-IncI2 to an IncI1 plasmid. All three hybrid
bla
CTX-M
genes may have resulted from recombination between
bla
CTX-M-14
and
bla
CTX-M-15
with a 45-bp spacer on an IncI2 plasmid. Five additional
Escherichia coli
isolates of different sequence types from different provinces, farms, and/or animals had
bla
CTX-M-64
on a pHNAH46-1-like IncI2 plasmid and 9 had
bla
CTX-M-123
on a pHNAH4-1-like IncI1 ST108 plasmid. Thus, epidemic IncI plasmids may be responsible for the spread of
bla
CTX-M-64
and
bla
CTX-M-123
between different animals and different locations in China.
MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a Staphylococcus aureus Immunocompromised Pneumonia Model
Authors: Hua L. , Cohen T. S. , Shi Y. , Datta V. , Hilliard J. J. , Tkaczyk C. , Suzich J. , Stover C. K. , Sellman B. R. 
Published: May 2015

ABSTRACT

Immunocompromised individuals are at increased risk of
Staphylococcus aureus
pneumonia. Neutralization of alpha-toxin (AT) with the monoclonal antibody (MAb) MEDI4893* protects normal mice from
S. aureus
pneumonia; however, the effects of the MAb in immunocompromised mice have not been reported. In this study, passive immunization with MEDI4893* increased survival rates and reduced bacterial numbers in the lungs in an immunocompromised murine
S. aureus
pneumonia model. Lungs from infected mice exhibited alveolar epithelial damage, protein leakage, and bacterial overgrowth, whereas lungs from mice passively immunized with MEDI4893* retained a healthy architecture, with an intact epithelial barrier. Adjunctive therapy or prophylaxis with a subtherapeutic MEDI4893* dose combined with subtherapeutic doses of vancomycin or linezolid improved survival rates, compared with the monotherapies. Furthermore, coadministration of MEDI4893* with vancomycin or linezolid extended the antibiotic treatment window. These data suggest that MAb-mediated neutralization of AT holds promise in strategies for prevention and adjunctive therapy among immunocompromised patients.
Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota
Authors: Rashid Mamun-Ur , Rosenborg Staffan , Panagiotidis Georgios , Söderberg-Löfdal Karin , Weintraub Andrej , Nord Carl Erik 
Published: May 2015

ABSTRACTCeftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. The purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. Fecal samples were collected on day −1 (within 24 h of the first infusion on day 1) and on days 2, 5, 7, 9, 14, and 21.Escherichia colinumbers decreased during the study and normalized on day 21. An increased number ofKlebsiellabacteria appeared on day 14 and normalized on day 21. The number of other enterobacteria decreased during the study, and the number of enterococci decreased from days 2 to 7 and normalized on day 9.Candidanumbers increased from days 5 to 9 and normalized after day 14. The number of lactobacilli decreased during the study and recovered on day 14. The number of bifidobacteria decreased on day 2 and normalized on day 21. The number ofBacteroidesbacteria was unchanged.Clostridium difficilenumbers decreased on days 7 and 9 and increased on days 14 and 21. A toxigenicC. difficilestrain was detected in one volunteer on day 21 with no reported adverse events. Plasma samples were collected on days −1, 2, 5, and 7. Ceftaroline and avibactam concentrations were 0 to 34.5 mg/liter and 0 to 61.6 mg/liter, respectively, in plasma and 0 to 35.4 mg/kg and 0 to 98.5 mg/kg, respectively, in feces. (This study is registered in the European Clinical Trials Database [https://eudract.ema.europa.eu/] under number EudraCT 2012 004921-25.)
Identification of New Natural CphA Metallo-β-Lactamases CphA4 and CphA5 in Aeromonas veronii and Aeromonas hydrophila Isolates from Municipal Sewage in Central Italy
Authors: Bottoni Carlo , Marcoccia Francesca , Compagnoni Chiara , Colapietro Martina , Sabatini Alessia , Celenza Giuseppe , Segatore Bernardetta , Maturo Maria Giovanna , Amicosante Gianfranco , Perilli Mariagrazia 
Published: May 2015

ABSTRACT

Two new natural CphA metallo-β-lactamases, the CphA4 and CphA5 enzymes, were identified in water samples from municipal sewage in central Italy. Compared to CphA, the CphA4 and CphA5 enzymes showed numerous point mutations. These enzymes have a narrow spectrum of substrates focused on carbapenems only. CphA5 showed
k
cat
values about 40-, 12-, and 97-fold higher than those observed for CphA4 versus imipenem, ertapenem, and biapenem, respectively.
The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis
Authors: Makarov Vadim , Neres João , Hartkoorn Ruben C. , Ryabova Olga B. , Kazakova Elena , Šarkan Michal , Huszár Stanislav , Piton Jérémie , Kolly Gaëlle S. , Vocat Anthony , Conroy Trent M. , Mikušová Katarína , Cole Stewart T. 
Published: May 2015

ABSTRACT

8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-
d
-ribose 2′-oxidase (DprE1) and display nanomolar bactericidal activity against
Mycobacterium tuberculosis
in vitro
. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against
M. tuberculosis
. These compounds inhibit DprE1 with 50% inhibitory concentration (IC
50
) values of <8 μM and present favorable
in vitro
absorption-distribution-metabolism-excretion/toxicity (ADME/T) and
in vivo
pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency.
Clonal Dissemination of OXA-370-Producing Klebsiella pneumoniae in Rio de Janeiro, Brazil
Authors: Pereira Polyana Silva , Borghi Mirla , de Araújo Carlos Felipe Machado , Aires Caio Augusto Martins , Oliveira Jane Cleide Ribeiro , Asensi Marise Dutra , Carvalho-Assef Ana Paula D'Alincourt 
Published: May 2015

ABSTRACTEnzymes of the OXA-48 family have become some of the most important beta-lactamases in the world. A new OXA-48 variant (OXA-370) was first described for anEnterobacter hormaecheistrain isolated in Rio Grande do Sul (southern region of Brazil) in 2013. Here we report detection of theblaOXA-370gene in 24 isolates belonging to threeEnterobacteriaceaespecies (22Klebsiella pneumoniaeisolates, 1Enterobacter cloacaeisolate, and 1Enterobacter aerogenesisolate) collected from five hospitals in Rio de Janeiro, Brazil, in 2013 and 2014. The isolates showed a multidrug resistance profile, and 12.5% were resistant to polymyxin B. BesidesblaOXA-370, no other carbapenemase genes were observed by PCR, whereasblaOXA-1was found in all isolates and 22 isolates (91.6%) possessedblaCTX-M-15. Molecular typing of theK. pneumoniaeisolates by pulsed-field gel electrophoresis (PFGE) showed the presence of two clonal groups, i.e., KpA (21 isolates) and KpB (1 isolate). KpA was characterized as sequence type 16 (ST16) and KpB as ST1041 by multilocus sequence typing (MLST). ST16 has been observed for KPC-producingK. pneumoniaein Rio de Janeiro. Plasmid analysis performed with six representative OXA-370-producing isolates showed plasmids harboring theblaOXA-370gene in all strains, ranging from 25 kb to 150 kb. This study suggests that there is an urgent need to investigate the presence of OXA-370 and dissemination of theK. pneumoniaeST16 clone carrying this gene in Brazil.
Cyclic di-GMP Modulates Gene Expression in Lyme Disease Spirochetes at the Tick-Mammal Interface To Promote Spirochete Survival during the Blood Meal and Tick-to-Mammal Transmission
Authors: Caimano Melissa J. , Dunham-Ems Star , Allard Anna M. , Cassera Maria B. , Kenedy Melisha , Radolf Justin D. 
Published: May 2015

ABSTRACT

Borrelia burgdorferi
, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of
B. burgdorferi
caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS;
B. burgdorferi
lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the
B. burgdorferi
Δ
glp
mutant had a markedly greater capacity to survive tick feeding than
B. burgdorferi
Δ
hk1
or Δ
rrp1
mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission.
An SOS Regulon under Control of a Noncanonical LexA-Binding Motif in the Betaproteobacteria
Authors: Sanchez-Alberola Neus , Campoy Susana , Emerson David , Barbé Jordi , Erill Ivan 
Published: May 2015

ABSTRACT

The SOS response is a transcriptional regulatory network governed by the LexA repressor that activates in response to DNA damage. In the
Betaproteobacteria
, LexA is known to target a palindromic sequence with the consensus sequence CTGT-N
8
-ACAG. We report the characterization of a LexA regulon in the iron-oxidizing betaproteobacterium
Sideroxydans lithotrophicus
.
In silico
and
in vitro
analyses show that LexA targets six genes by recognizing a binding motif with the consensus sequence GAACGaaCGTTC, which is strongly reminiscent of the
Bacillus subtilis
LexA-binding motif. We confirm that the closely related
Gallionella capsiferriformans
shares the same LexA-binding motif, and
in silico
analyses indicate that this motif is also conserved in the
Nitrosomonadales
and the
Methylophilales
. Phylogenetic analysis of LexA and the alpha subunit of DNA polymerase III (DnaE) reveal that the organisms harboring this noncanonical LexA form a compact taxonomic cluster within the
Betaproteobacteria
. However, their
lexA
gene is unrelated to the standard
Betaproteobacteria
lexA
, and there is evidence of its spread through lateral gene transfer. In contrast to other reported cases of noncanonical LexA-binding motifs, the regulon of
S. lithotrophicus
is comparable in size and function to that of many other
Betaproteobacteria
, suggesting that a convergent SOS regulon has reevolved under the control of a new LexA protein. Analysis of the DNA-binding domain of
S. lithotrophicus
LexA reveals little sequence similarity with that of other LexA proteins targeting similar binding motifs, suggesting that network structure may limit site evolution or that structural constrains make the
B. subtilis
-type motif an optimal interface for multiple LexA sequences.

IMPORTANCE
Understanding the evolution of transcriptional systems enables us to address important questions in microbiology, such as the emergence and transfer potential of different regulatory systems to regulate virulence or mediate responses to stress. The results reported here constitute the first characterization of a noncanonical LexA protein regulating a standard SOS regulon. This is significant because it illustrates how a complex transcriptional program can be put under the control of a novel transcriptional regulator. Our results also reveal a substantial degree of plasticity in the LexA recognition domain, raising intriguing questions about the space of protein-DNA interfaces and the specific evolutionary constrains faced by these elements.
Acupuncture for functional constipation: protocol of an individual patient data meta-analysis
Authors: Zheng Qianhua , Zheng Hui , Lu Lingyun , Leng Jincheng , Zhou Siyuan , Zheng Huabin , Huang Wenjing , Liu Zhishun , Zhu Bing , Li Ying 
Published: May 2015

IntroductionFunctional constipation (FC) is a common gastrointestinal disease. Systematic reviews indicate that acupuncture may be effective for patients with FC. However, this conclusion is not convincing due to the quality, sample size and methodological heterogeneity of the studies included by these systematic reviews. Therefore, it is necessary for us to conduct a meta-analysis of individual patient data (IPD) from high-quality clinical trials to determine whether acupuncture is effective for patients with FC.Methods and analysisRandomised controlled trials (RCTs) of acupuncture for adult patients with FC will be searched in several databases from inception to April 2015. The corresponding authors of eligible studies will be contacted and invited to contribute raw data. The primary outcome is the change in spontaneous defaecation per week from baseline. The secondary outcomes include the proportion of responders, changes in stool quality, mean transit time, proportion of patients using laxatives and adverse events. We will check all of the data and perform reanalysis according to the statistical methodology reported in previous publications. Then we will harmonise the raw data and use a two-step method to conduct the IPD meta-analysis. First, we will calculate the effect size of acupuncture of each trial by analysis of covariance, with the principal end point as the dependent variable and the baseline scores as the covariates. Second, the effect size of acupuncture in each original study will be combined in the meta-analysis.DisseminationOn the basis of the IPD meta-analysis of high-quality RCTs, this review will answer the question of whether acupuncture is effective for FC. The findings of the review will be disseminated through peer-review publications and conference presentations.Trial registration numberPROSPERO 2014 CRD42014009901.
Understanding patient experiences of self-managing chronic dizziness: a qualitative study of booklet-based vestibular rehabilitation, with or without remote support
Authors: Muller Ingrid , Kirby Sarah , Yardley Lucy 
Published: May 2015

ObjectiveThis study explores participants’ experience of self-management of dizziness using booklet-based vestibular rehabilitation (VR), with or without expert telephone support.DesignSemistructured qualitative interviews were conducted.SettingParticipants were recruited from primary care practices as part of a large RCT.ParticipantsInterviews were carried out with 33 people (10 men and 23 women; age 27–84) self-managing chronic dizziness using booklet-based vestibular rehabilitation, with or without expert telephone support.ResultsData were analysed using inductive thematic analysis. The majority of participants in both groups reported a positive experience of VR therapy, with many participants reporting an improvement in their dizziness symptoms since undertaking the therapy. Participants in the telephone support group felt that a genuine relationship developed between them and their therapist within three short sessions, and described their therapy sessions as reassuring, encouraging and motivational.ConclusionsThe VR treatment booklet appears to be a valued tool for self-managing chronic dizziness and people appreciate receiving remote telephone support.Trial registration numberNCT00732797.
What factors contribute to positive early childhood health and development in Australian Aboriginal children? Protocol for a population-based cohort study using linked administrative data (The Seeding Success Study)
Authors: Falster Kathleen , Jorm Louisa , Eades Sandra , Lynch John , Banks Emily , Brownell Marni , Craven Rhonda , Einarsdóttir Kristjana , Randall Deborah 
Published: May 2015

IntroductionAustralian Aboriginal children are more likely than non-Aboriginal children to have developmental vulnerability at school entry that tracks through to poorer literacy and numeracy outcomes and multiple social and health disadvantages in later life. Empirical evidence identifying the key drivers of positive early childhood development in Aboriginal children, and supportive features of local communities and early childhood service provision, are lacking.Methods and analysisThe study population will be identified via linkage of Australian Early Development Census data to perinatal and birth registration data sets. It will include an almost complete population of children who started their first year of full-time school in New South Wales (NSW), Australia, in 2009 and 2012. Early childhood health and development trajectories for these children will be constructed via linkage to a range of administrative data sets relating to birth outcomes, congenital conditions, hospital admissions, emergency department presentations, receipt of ambulatory mental healthcare services, use of general practitioner services, contact with child protection and out-of-home care services, receipt of income assistance and fact of death. Using multilevel modelling techniques, we will quantify the contributions of individual-level and area-level factors to variation in early childhood development outcomes in Aboriginal and non-Aboriginal children. Additionally, we will evaluate the impact of two government programmes that aim to address early childhood disadvantage, the NSW Aboriginal Maternal and Infant Health Service and the Brighter Futures Program. These evaluations will use propensity score matching methods and multilevel modelling.Ethics and disseminationEthical approval has been obtained for this study. Dissemination mechanisms include engagement of stakeholders (including representatives from Aboriginal community controlled organisations, policy agencies, service providers) through a reference group, and writing of summary reports for policy and community audiences in parallel with scientific papers.
Exploring demographic and lifestyle associations with patient experience following telephone triage by a primary care doctor or nurse: secondary analyses from a cluster randomised controlled trial
Authors: Warren Fiona C , Calitri Raff , Fletcher Emily , Varley Anna , Holt Tim A , Lattimer Valerie , Richards David , Richards Suzanne , Salisbury Chris , Taylor Rod S , Campbell John L 
Published: May 2015

BackgroundThe ESTEEM trial was a cluster randomised controlled trial that compared two telephone triage management systems (general practitioner (GP) or a nurse supported by computer decision support software) with usual care, in response to a request for same-day consultation in general practice.AimTo investigate associations between trial patients’ demographic, health, and lifestyle characteristics, and their reported experiences of care.SettingRecruitment of 20 990 patients occurred between May 2011 and December 2012 in 42 GP practices in England (13 GP triage, 15 nurse triage, 14 usual care).MethodPatients reported their experiences via a postal questionnaire issued 4 weeks after their initial request for a same-day consultation. Overall satisfaction, ease of accessing medical help/advice, and convenience of care were analysed using linear hierarchical modelling.ResultsQuestionnaires were returned by 12 132 patients (58%). Older patients reported increased overall satisfaction compared with patients aged 25–59 years, but patients aged 16–24 years reported lower satisfaction. Compared with white patients, patients from ethnic minorities reported lower satisfaction in all three arms, although to a lesser degree in the GP triage arm. Patients from ethnic minorities reported higher satisfaction in the GP triage than in usual care, whereas white patients reported higher satisfaction with usual care. Patients unable to take time away from work or who could only do so with difficulty reported lower satisfaction across all three trial arms.ConclusionsPatient characteristics, such as age, ethnicity and ability to attend their practice during work hours, were associated with their experiences of care following a same-day consultation request in general practice. Telephone triage did not increase satisfaction among patients who were unable to attend their practice during working hours.Trial registration numberISCRTN20687662.