bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased risk of breakthrough infection among cytomegalovirus donor‐positive/recipient‐negative kidney transplant recipients receiving lower‐dose valganciclovir prophylaxis
Authors: Stevens D.R. , Sawinski D. , Blumberg E. , Galanakis N. , Bloom R.D. , Trofe‐Clark J. 
Published: February 2015

AbstractObjectiveWe compared the effectiveness of lower‐dose (LD) (450 mg/day for 6 months) to standard‐dose (SD) (900 mg/day for 6 months) valganciclovir (VGCV) prophylaxis for prevention of cytomegalovirus (CMV) infection and disease in high‐risk CMV donor‐positive/recipient‐negative (D+/R−) kidney recipients.MethodsWe performed a single‐center, retrospective cohort study, in a 750‐bed academic medical center, involving a total of 90 evaluable CMV high‐risk kidney recipients. All patients were retrospectively followed from day of transplantation to November 1, 2012, or to the development of CMV infection or disease, death, or loss to follow‐up. CMV screening was only done if suggestive symptoms or abnormal laboratory values were present. Our immunosuppressive protocol otherwise did not differ between periods.ResultsIn total, 45 consecutive eligible patients initiated SD prophylaxis in the 22 months before the institutional protocol change regarding CMV prophylaxis. One patient developed CMV infection in the setting of non‐adherence. In the 16 months after the protocol update, 45 consecutive eligible patients receiving LD prophylaxis were evaluated: 6 developed CMV infection while receiving prophylaxis (P = 0.11). Ganciclovir (GCV)‐resistant infection was confirmed in 1 patient in the LD prophylaxis group. Late‐onset CMV infection or disease occurred in 11 patients (24%) in the SD group and in 12 patients (27%) in the LD group (P = 0.86). More patients in the SD group developed leukopenia (75% vs. 44%, P < 0.01). During the study period, no significant differences were seen between the groups in mean mg/kg exposure to rabbit anti‐thymocyte globulin induction courses, mean tacrolimus troughs, number of rejection episodes, mean estimated renal function, graft survival, or patient survival. Overall mean follow‐up (± standard deviation) was 357 days (± 53) in the SD group and 320 days (± 103) in the LD group (P = 0.03).ConclusionBreakthrough CMV infection while receiving VGCV prophylaxis occurred more often after the institutional protocol revision to LD VGCV prophylaxis. Given our concern for increased risk of breakthrough infection and GCV resistance when prophylaxis is under‐dosed, our institutional protocols were revised back to SD prophylaxis for all CMV D+/R− kidney transplant recipients.
Expression activation and functional analysis of HLA3, a putative inorganic carbon transporter in Chlamydomonas reinhardtii
Authors: Gao Han , Wang Yingjun , Fei Xiaowen , Wright David A. , Spalding Martin H. 
Published: February 2015

SummaryThe CO2 concentrating mechanism (CCM) is a key component of the carbon assimilation strategy of aquatic microalgae. Induced by limiting CO2 and tightly regulated, the CCM enables these microalgae to respond rapidly to varying environmental CO2 supplies and to perform photosynthetic CO2 assimilation in a cost‐effective way. A functional CCM in eukaryotic algae requires Rubisco sequestration, rapid interconversion between CO2 and catalyzed by carbonic anhydrases (CAs), and active inorganic carbon (Ci) uptake. In the model microalga Chlamydomonas reinhardtii, a membrane protein HLA3 is proposed to be involved in active Ci uptake across the plasma membrane. In this study, we use an artificially designed transcription activator‐like effector (dTALE) to activate the expression of HLA3. The successful activation of HLA3 expression demonstrates dTALE as a promising tool for gene‐specific activation and investigation of gene function in Chlamydomonas. Activation of HLA3 expression in high CO2 acclimated cells, where HLA3 is not expressed, resulted in increased Ci accumulation and Ci‐dependent photosynthetic O2 evolution specifically in very low CO2 concentrations, which confirms that HLA3 is indeed involved in Ci uptake, and suggests it is mainly associated with transport in very low CO2 concentrations, conditions in which active CO2 uptake is highly limited.
First Report of Macrolide Resistance Gene
erm
(T) Harbored by a Novel Small Plasmid from Erysipelothrix rhusiopathiae
Authors: Xu Chang-Wen , Zhang An-Yun , Yang Chun-Mei , Pan Yun , Guan Zhong-Bin , Lei Chang-Wei , Peng Lin-Yao , Li Qing-Zhou , Wang Hong-Ning 
Published: February 2015

ABSTRACT

The macrolide resistance gene
erm
(T) was identified for the first time in a porcine
Erysipelothrix rhusiopathiae
isolate from swine in China. The novel 3,749-bp small plasmid pER29, which carries
erm
(T), had a G+C content of 31% and four distinct open reading frames. The presence of pER29 increased by at least 128-fold the MICs of clindamycin and erythromycin for
E. rhusiopathiae
. The fitness cost of pER29 could be responsible for the low frequency of
erm
(T) in
E. rhusiopathiae
.
Factors Influencing Culture Positivity in Pyogenic Vertebral Osteomyelitis Patients with Prior Antibiotic Exposure
Authors: Kim Chung-Jong , Kang Seung-Ji , Yoon Doran , Lee Myung Jin , Kim Moonsuk , Song Kyoung-Ho , Jang Hee-Chang , Jung Sook-In , Kim Eu Suk , Kim Hong Bin , Oh Myoung-don , Park Kyung-Hwa , Kim Nam Joong 
Published: February 2015

ABSTRACT
We conducted a retrospective cohort study to evaluate factors influencing tissue culture positivity in patients with pyogenic vertebral osteomyelitis exposed to antibiotics before diagnosis. Tissue culture was positive in 48.3% (28/58) of the patients, and the median antibiotic-free period was 1.5 days (range, 0.7 to 5.7 days). In a multivariate analysis, a higher C-reactive protein (CRP) level (adjusted odds ratio [aOR], 1.18; 95% confidence interval, 1.07 to 1.29) and open surgical biopsy (aOR, 6.33; 95% confidence interval, 1.12 to 35.86) were associated with tissue culture positivity.
Use of
In Vitro
Vancomycin Testing Results To Predict Susceptibility to Oritavancin, a New Long-Acting Lipoglycopeptide
Authors: Jones Ronald N. , Turnidge John D. , Moeck Greg , Arhin Francis F. , Mendes Rodrigo E. 
Published: February 2015

ABSTRACT

Oritavancin is a recently approved lipoglycopeptide antimicrobial agent with activity against Gram-positive pathogens. Its extended serum elimination half-life and concentration-dependent killing enable single-dose treatment of acute bacterial skin and skin structure infections. At the time of regulatory approval, new agents, including oritavancin, are not offered in the most widely used susceptibility testing devices and therefore may require application of surrogate testing using a related antimicrobial to infer susceptibility. To evaluate vancomycin as a predictive susceptibility marker for oritavancin, 26,993 recent Gram-positive organisms from U.S. and European hospitals were tested using reference MIC methods. Organisms included
Staphylococcus aureus
, coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci (BHS), viridans group streptococci (VGS), and enterococci (ENT). These five major pathogen groups were analyzed by comparing results with FDA-approved susceptible breakpoints for both drugs, as well as those suggested by epidemiological cutoff values and supported by pharmacokinetic/pharmacodynamic analyses. Vancomycin susceptibility was highly accurate (98.1 to 100.0%) as a surrogate for oritavancin susceptibility among the indicated pathogen species. Furthermore, direct MIC comparisons showed high oritavancin potencies, with vancomycin/oritavancin MIC
90
results of 1/0.06, 2/0.06, 0.5/0.12,1/0.06, and >16/0.06 μg/ml for
S. aureus
, CoNS, BHS, VGS, and ENT, respectively. In conclusion, vancomycin demonstrated acceptable accuracy as a surrogate marker for predicting oritavancin susceptibility when tested against the indicated pathogens. In contrast, 93.3% of vancomycin-nonsusceptible enterococci had oritavancin MIC values of ≤0.12 μg/ml, indicating a poor predictive value of vancomycin for oritavancin resistance against these organisms. Until commercial oritavancin susceptibility testing devices are readily available, isolates that when tested show vancomycin susceptibility can be inferred to be susceptible to oritavancin by using FDA-approved breakpoints.
Emergence of the First Levofloxacin-Resistant Strains of Streptococcus agalactiae Isolated in Italy
Authors: Piccinelli G. , Gargiulo F. , Corbellini S. , Ravizzola G. , Bonfanti C. , Caruso A. , De Francesco M. A. 
Published: February 2015

ABSTRACT

Of 901 group B streptococcus strains analyzed, 13 (1.4%) were resistant to levofloxacin (MICs of >32 μg/ml for seven isolates, 2 μg/ml for four isolates, and 1.5 μg/ml for four isolates). Mutations in the quinolone resistance-determining regions (QRDRs) of gyrase and topoisomerase IV were identified. A double mutation involving the Ser-81 change to Leu for
gyrA
and the Ser-79 change to Phe or to Tyr for
parC
was linked to a high level of fluoroquinolone resistance. In addition, two other mutational positions in
parC
were observed, resulting in an Asp-83-to-Tyr substitution and an Asp-83-to-Asn substitution. Different mutations were also observed in
gyrB
, with unknown significance. Most levofloxacin-resistant GBS strains were of serotype Ib and belonged to sequence type 19 (ST19) and clonal complex 19 (CC-19). Most of them exhibited the
epsilon
gene.
Antimicrobial Peptides Expressed in Medicinal Maggots of the Blow Fly Lucilia sericata Show Combinatorial Activity against Bacteria
Authors: Pöppel Anne-Kathrin , Vogel Heiko , Wiesner Jochen , Vilcinskas Andreas 
Published: February 2015

ABSTRACT

The larvae of the common green bottle fly (
Lucilia sericata
) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that
L. sericata
larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs.
L. sericata
AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including
Pseudomonas aeruginosa
,
Proteus vulgaris
, and
Enterococcus faecalis
. Against
Escherichia coli
(Gram negative) and
Micrococcus luteus
(Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages.
Interstrain Interactions between Bacteria Isolated from Vacuum-Packaged Refrigerated Beef
Authors: Zhang Peipei , Baranyi József , Tamplin Mark 
Published: February 2015

ABSTRACT

The formation of bacterial spoilage communities in food is influenced by both extrinsic and intrinsic environmental factors. Although many reports describe how these factors affect bacterial growth, much less is known about interactions among bacteria, which may influence community structure. This study investigated interactions among representative species of bacteria isolated from vacuum-packaged (VP) beef. Thirty-nine effectors and 20 target isolates were selected, representing 10 bacterial genera:
Carnobacterium
,
Pseudomonas
,
Hafnia
,
Serratia
,
Yersinia
,
Rahnella
,
Brochothrix
,
Bacillus
,
Leuconostoc
, and
Staphylococcus
. The influence of live effectors on growth of target isolates was measured by spot-lawn agar assay and also in liquid culture medium broth using live targets and effector cell-free supernatants. Inhibition on agar was quantified by diameter of inhibition zone and in broth by measuring detection time, growth rate, and maximum population density. A number of interactions were observed, with 28.6% of isolates inhibiting and 4.2% promoting growth. The majority of
Pseudomonas
isolates antagonized growth of approximately one-half of target isolates. Two
Bacillus
spp. each inhibited 16 targets. Among lactic acid bacteria (LAB),
Carnobacterium maltaromaticum
inhibited a wider range of isolates compared to other LAB. The majority of effector isolates enhancing target isolate growth were Gram-negative, including
Pseudomonas
spp. and
Enterobacteriaceae
. These findings markedly improve the understanding of potential interactions among spoilage bacteria, possibly leading to more mechanistic descriptions of bacterial community formation in VP beef and other foods.
The Importance of the Pseudomonas aeruginosa Type III Secretion System in Epithelium Traversal Depends upon Conditions of Host Susceptibility
Authors: Sullivan Aaron B. , Tam K. P. Connie , Metruccio Matteo M. E. , Evans David J. , Fleiszig Suzanne M. J. 
Published: February 2015

ABSTRACT

Pseudomonas aeruginosa
is invasive or cytotoxic to host cells, depending on the type III secretion system (T3SS) effectors encoded. While the T3SS is known to be involved in disease
in vivo
, how it participates remains to be clarified. Here, mouse models of superficial epithelial injury (tissue paper blotting with EGTA treatment) and immunocompromise (MyD88 deficiency) were used to study the contribution of the T3SS transcriptional activator ExsA to epithelial traversal. Corneas of excised eyeballs were inoculated with green fluorescent protein (GFP)-expressing PAO1 or isogenic
exsA
mutants for 6 h
ex vivo
before bacterial traversal and epithelial thickness were quantified by using imaging. In the blotting-EGTA model,
exsA
mutants were defective in capacity for traversal. Accordingly, an ∼16-fold variability in
exsA
expression among PAO1 isolates from three sources correlated with epithelial loss. In contrast, MyD88
−/−
epithelia remained susceptible to
P. aeruginosa
traversal despite
exsA
mutation. Epithelial lysates from MyD88
−/−
mice had reduced antimicrobial activity compared to those from wild-type mice with and without prior antigen challenge, particularly 30- to 100-kDa fractions, for which mass spectrometry revealed multiple differences, including (i) lower baseline levels of histones, tubulin, and lumican and (ii) reduced glutathione
S
-transferase, annexin, and dermatopontin, after antigen challenge. Thus, the importance of ExsA in epithelial traversal by invasive
P. aeruginosa
depends on the compromise enabling susceptibility, suggesting that strategies for preventing infection will need to extend beyond targeting the T3SS. The data also highlight the importance of mimicking conditions allowing susceptibility in animal models and the need to monitor variability among bacterial isolates from different sources, even for the same strain.
Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition
Authors: Beatson Scott A. , Ben Zakour Nouri L. , Totsika Makrina , Forde Brian M. , Watts Rebecca E. , Mabbett Amanda N. , Szubert Jan M. , Sarkar Sohinee , Phan Minh-Duy , Peters Kate M. , Petty Nicola K. , Alikhan Nabil-Fareed , Sullivan Mitchell J. , Gawthorne Jayde A. , Stanton-Cook Mitchell , Nhu Nguyen Thi Khanh , Chong Teik Min , Yin Wai-Fong , Chan Kok-Gan , Hancock Viktoria , Ussery David W. , Ulett Glen C. , Schembri Mark A. 
Published: February 2015

ABSTRACT

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with
Escherichia coli
responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU
E. coli
strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles
E. coli
K-12, with the addition of a 94-kb genomic island (GI-VR50-
pheV
), eight prophages, and multiple plasmids. GI-VR50-
pheV
has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-
pheV
deleted was attenuated in a mouse model of UTI
in vivo
. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants.
E. coli
VR50
afa
and VR50
afaE
displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50
afa
and VR50
afaE
displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-
pheV
mutant. Our study suggests that
E. coli
VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.
Toll-Like Receptor 2 (TLR2) and TLR9 Play Opposing Roles in Host Innate Immunity against Salmonella enterica Serovar Typhimurium Infection
Authors: Zhan Renhui , Han Qiuju , Zhang Cai , Tian Zhigang , Zhang Jian 
Published: February 2015

ABSTRACTToll-like receptors (TLRs) are evolutionarily conserved host proteins that are essential for effective host defense against pathogens. However, recent studies suggest that some TLRs can negatively regulate immune responses. We observed here that TLR2 and TLR9 played opposite roles in regulating innate immunity against oral infection ofSalmonella entericaserovar Typhimurium in mice. WhileTLR9−/−mice exhibited shortened survival, an increased cytokine storm, and more severeSalmonellahepatitis than wild-type (WT) mice,TLR2−/−mice exhibited the opposite phenomenon. Further studies demonstrated that TLR2 deficiency and TLR9 deficiency in macrophages both disrupted NK cell cytotoxicity againstS. Typhimurium-infected macrophages by downregulating NK cell degranulation and gamma interferon (IFN-γ) production through decreased macrophage expression of the RAE-1 NKG2D ligand. But more importantly, we found thatS. Typhimurium-infectedTLR2−/−macrophages upregulated inducible nitric oxide synthase (iNOS) expression, resulting in a lower bacterial load than that in WT macrophagesin vitroand liversin vivoas well as low proinflammatory cytokine levels. In contrast,TLR9−/−macrophages showed decreased reactive oxygen species (ROS) expression concomitant with a high bacterial load in the macrophages and in livers ofTLR9−/−mice.TLR9−/−macrophages were also more susceptible than WT macrophages toS. Typhimurium-induced necroptosisin vitro, likely contributing to bacterial spread and transmissionin vivo. Collectively, these findings indicate that TLR2 negatively regulates anti-S. Typhimurium immunity, whereas TLR9 is vital to host defense and survival againstS. Typhimurium invasion. TLR2 antagonists or TLR9 agonists may thus serve as potential anti-S. Typhimurium therapeutic agents.
The Class II Phosphatidylinositol 3-Phosphate Kinase PIK3C2A Promotes Shigella flexneri Dissemination through Formation of Vacuole-Like Protrusions
Authors: Dragoi Ana-Maria , Agaisse Hervé 
Published: February 2015

ABSTRACTIntracellular pathogens such asShigella flexneriandListeria monocytogenesachieve dissemination in the intestinal epithelium by displaying actin-based motility in the cytosol of infected cells. As they reach the cell periphery, motile bacteria form plasma membrane protrusions that resolve into vacuoles in adjacent cells, through a poorly understood mechanism. Here, we report on the role of the class II phosphatidylinositol 3-phosphate kinase PIK3C2A inS. flexneridissemination. Time-lapse microscopy revealed that PIK3C2A was required for the resolution of protrusions into vacuoles through the formation of an intermediate membrane-bound compartment that we refer to as a vacuole-like protrusion (VLP). Genetic rescue of PIK3C2A depletion with RNA interference (RNAi)-resistant cDNA constructs demonstrated that VLP formation required the activity of PIK3C2A in primary infected cells. PIK3C2A expression was required for production of phosphatidylinositol 3-phosphate [PtdIns(3)P] at the plasma membrane surrounding protrusions. PtdIns(3)P production was not observed in the protrusions formed byL. monocytogenes, whose dissemination did not rely on PIK3C2A. PIK3C2A-mediated PtdIns(3)P production inS. flexneriprotrusions was regulated by host cell tyrosine kinase signaling and relied on the integrity of theS. flexneritype 3 secretion system (T3SS). We suggest a model ofS. flexneridissemination in which the formation of VLPs is mediated by the PIK3C2A-dependent production of the signaling lipid PtdIns(3)P in the protrusion membrane, which relies on the T3SS-dependent activation of tyrosine kinase signaling in protrusions.
Analysis of the σ
E
Regulon in Crohn's Disease-Associated Escherichia coli Revealed Involvement of the
waaWVL
Operon in Biofilm Formation
Authors: Chassaing Benoit , Garénaux Estelle , Carriere Jessica , Rolhion Nathalie , Guérardel Yann , Barnich Nicolas , Bonnet Richard , Darfeuille-Michaud Arlette 
Published: February 2015

ABSTRACT

Ileal lesions of patients with Crohn's disease are colonized by adherent-invasive
Escherichia coli
(AIEC), which is able to adhere to and to invade intestinal epithelial cells (IEC), to replicate within macrophages, and to form biofilms on the surface of the intestinal mucosa. Previous analyses indicated the involvement of the σ
E
pathway in AIEC-IEC interaction, as well as in biofilm formation, with σ
E
pathway inhibition leading to an impaired ability of AIEC to colonize the intestinal mucosa and to form biofilms. The aim of this study was to characterize the σ
E
regulon of AIEC strain LF82 in order to identify members involved in AIEC phenotypes. Using comparative
in silico
analysis of the σ
E
regulon, we identified the
waaWVL
operon as a new member of the σ
E
regulon in reference AIEC strain LF82. We determined that the
waaWVL
operon is involved in AIEC lipopolysaccharide structure and composition, and the
waaWVL
operon was found to be essential for AIEC strains to produce biofilm and to colonize the intestinal mucosa.

IMPORTANCE
An increased prevalence of adherent-invasive
Escherichia coli
(AIEC) bacteria was previously observed in the intestinal mucosa of Crohn's disease (CD) patients, and clinical observations revealed bacterial biofilms associated with the mucosa of CD patients. Here, analysis of the σ
E
regulon in AIEC and commensal
E. coli
identified 12 genes controlled by σ
E
only in AIEC. Among them, WaaWVL factors were found to play an essential role in biofilm formation and mucosal colonization by AIEC. In addition to identifying molecular tools that revealed a pathogenic population of
E. coli
colonizing the mucosa of CD patients, these results indicate that targeting the
waaWVL
operon could be a potent therapeutic strategy to interfere with the ability of AIEC to form biofilms and to colonize the gut mucosa.