bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence of Extensively Drug-Resistant Proteus mirabilis Harboring a Conjugative NDM-1 Plasmid and a Novel Salmonella Genomic Island 1 Variant, SGI1-Z
Authors: Qin Shangshang , Qi Hui , Zhang Qijing , Zhao Di , Liu Zhen-Zhen , Tian Hao , Xu Lijuan , Xu Hui , Zhou Mengmeng , Feng Xianju , Liu Hong-Min 
Published: July 2015

ABSTRACT

Acquisition of
bla
NDM-1
in bacterial species, such as
Proteus mirabilis
that is intrinsically resistant to tetracycline, tigecycline and colistin, will make clinical treatment extremely difficult. Here, we characterized an NDM-1-producing clinical isolate of
P. mirabilis
(PM58) that displayed an extensively drug-resistant (XDR) phenotype, susceptible only to aztreonam. Molecular analysis revealed that PM58 harbored both a conjugative NDM-1 plasmid and a novel
Salmonella
genomic island 1 variant on chromosome.
Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans
Authors: Li Xiuyun , Hou Yinglong , Yue Longtao , Liu Shuyuan , Du Juan , Sun Shujuan 
Published: July 2015

ABSTRACT

Fungal infections, especially infections caused by
Candida albicans
, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in
C. albicans
are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in
C. albicans
and examines potential targets for the development of new antifungal drugs.
Carriage of Escherichia coli Producing CTX-M-Type Extended-Spectrum β-Lactamase in Healthy Vietnamese Individuals
Authors: Bui Thi Mai Huong , Hirai Itaru , Ueda Shuhei , Bui Thi Kim Ngan , Hamamoto Kouta , Toyosato Takehiko , Le Danh Tuyen , Yamamoto Yoshimasa 
Published: July 2015

ABSTRACT

Healthy carriage of CTX-M-type extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
was examined by thrice collecting fecal samples from the same 199 healthy Vietnamese subjects every 6 months. Using pulsed-field gel electrophoresis (PFGE), identical PFGE patterns throughout the three samplings were not observed, although prevalence of
E. coli
in the subjects was around 50% in the three samplings. Our results suggested a short carriage period of the CTX-M-type ESBL-producing
E. coli
in healthy Vietnamese subjects.
Antimicrobial Activity of Fosfomycin-Tobramycin Combination against Pseudomonas aeruginosa Isolates Assessed by Time-Kill Assays and Mutant Prevention Concentrations
Authors: Díez-Aguilar María , Morosini María Isabel , Tedim Ana P. , Rodríguez Irene , Aktaş Zerrin , Cantón Rafael 
Published: July 2015

ABSTRACT

The antibacterial activity of fosfomycin-tobramycin combination was studied by time-kill assay in eight
Pseudomonas aeruginosa
clinical isolates belonging to the fosfomycin wild-type population (MIC = 64 μg/ml) but with different tobramycin susceptibilities (MIC range, 1 to 64 μg/ml). The mutant prevention concentration (MPC) and mutant selection window (MSW) were determined in five of these strains (tobramycin MIC range, 1 to 64 μg/ml) in aerobic and anaerobic conditions simulating environments that are present in biofilm-mediated infections. Fosfomycin-tobramycin was synergistic and bactericidal for the isolates with mutations in the
mexZ
repressor gene, with a tobramycin MIC of 4 μg/ml. This effect was not observed in strains displaying tobramycin MICs of 1 to 2 μg/ml due to the strong bactericidal effect of tobramycin alone. Fosfomycin presented higher MPC values (range, 2,048 to >2,048 μg/ml) in aerobic and anaerobic conditions than did tobramycin (range, 16 to 256 μg/ml). Interestingly, the association rendered narrow or even null MSWs in the two conditions. However, for isolates with high-level tobramycin resistance that harbored aminoglycoside nucleotidyltransferases, time-kill assays showed no synergy, with wide MSWs in the two environments.
glpT
gene mutations responsible for fosfomycin resistance in
P. aeruginosa
were determined in fosfomycin-susceptible wild-type strains and mutant derivatives recovered from MPC studies. All mutant derivatives had changes in the GlpT amino acid sequence, which resulted in a truncated permease responsible for fosfomycin resistance. These results suggest that fosfomycin-tobramycin can be an alternative for infections due to
P. aeruginosa
since it has demonstrated synergistic and bactericidal activity in susceptible isolates and those with low-level tobramycin resistance. It also prevents the emergence of resistant mutants in either aerobic or anaerobic environments.
Potent
Ex Vivo
Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax
Authors: Wirjanata Grennady , Sebayang Boni F. , Chalfein Ferryanto , Prayoga  , Handayuni Irene , Trianty Leily , Kenangalem Enny , Noviyanti Rintis , Campo Brice , Poespoprodjo Jeanne Rini , Möhrle Jörg J. , Price Ric N. , Marfurt Jutta 
Published: July 2015

ABSTRACT

The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent
in vitro
efficacies against
Plasmodium falciparum
, but susceptibility data for
P. vivax
are limited. The species- and stage-specific
ex vivo
activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant
P. falciparum
and
P. vivax
are prevalent. Both compounds were highly active against
P. falciparum
(median [range] 50% inhibitory concentration [IC
50
]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and
P. vivax
(NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC
50
s in parasites exposed at the trophozoite stage than at the ring stage for NQ in
P. falciparum
(26.5 versus 5.1 nM,
P
= 0.021) and
P. vivax
(341.6 versus 6.5 nM,
P
= 0.021) and for MB in
P. vivax
(10.1 versus 1.6 nM,
P
= 0.010). The excellent
ex vivo
activities of NQ and MB against both
P. falciparum
and
P. vivax
highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.
Effective Antibiofilm Polyketides against Staphylococcus aureus from the Pyranonaphthoquinone Biosynthetic Pathways of Streptomyces Species
Authors: Oja Terhi , San Martin Galindo Paola , Taguchi Takaaki , Manner Suvi , Vuorela Pia M. , Ichinose Koji , Metsä-Ketelä Mikko , Fallarero Adyary 
Published: July 2015

ABSTRACT

Streptomyces
bacteria are renowned for their ability to produce bioactive secondary metabolites. Recently, synthetic biology has enabled the production of intermediates and shunt products, which may have altered biological activities compared to the end products of the pathways. Here, we have evaluated the potential of recently isolated alnumycins and other closely related pyranonaphthoquinone (PNQ) polyketides against
Staphylococcus aureus
biofilms. The antimicrobial potency of the compounds against planktonic cells and biofilms was determined by redox dye-based viability staining, and the antibiofilm efficacy of the compounds was confirmed by viable counting. A novel antistaphylococcal polyketide, alnumycin D, was identified. Unexpectedly, the
C
-ribosylated pathway shunt product alnumycin D was more active against planktonic and biofilm cells than the pathway end product alnumycin A, where a ribose unit has been converted into a dioxane moiety. The evaluation of the antibiofilm potential of other alnumycins revealed that the presence of the ribose moiety in pyranose form is essential for high activity against preformed biofilms. Furthermore, the antibiofilm potential of other closely related PNQ polyketides was examined. Based on their previously reported activity against planktonic
S. aureus
cells, granaticin B, kalafungin, and medermycin were also selected for testing, and among them, granaticin B was found to be the most potent against preformed biofilms. The most active antibiofilm PNQs, alnumycin D and granaticin B, share several structural features that may be important for their antibiofilm activity. They are uncharged, glycosylated, and also contain a similar oxygenation pattern of the lateral naphthoquinone ring. These findings highlight the potential of antibiotic biosynthetic pathways as a source of effective antibiofilm compounds.
Subinhibitory Doses of Aminoglycoside Antibiotics Induce Changes in the Phenotype of Mycobacterium abscessus
Authors: Tsai Sheng-Hui , Lai Hsin-Chih , Hu Shiau-Ting 
Published: July 2015

ABSTRACT

Subinhibitory doses of antibiotics have been shown to cause changes in bacterial morphology, adherence ability, and resistance to antibiotics. In this study, the effects of subinhibitory doses of aminoglycoside antibiotics on
Mycobacterium abscessus
were investigated. The treatment of
M. abscessus
cells with subinhibitory doses of amikacin was found to change their colony from a smooth to a rough morphotype and increase their ability to adhere to a polyvinylchloride plate, aggregate in culture, and resist phagocytosis and killing by macrophages.
M. abscessus
cells treated with a subinhibitory dose of amikacin also became more potent in Toll-like receptor 2 (TLR-2) stimulation, leading to increased tumor necrosis factor alpha (TNF-α) production by macrophages. The MAB_3508c gene was shown to play a role in mediating these phenotypic changes, as its expression in
M. abscessus
cells was increased when they were treated with a subinhibitory dose of amikacin. In addition, overexpression of MAB_3508c in
M. abscessus
cells caused changes similar to those induced by subinhibitory doses of amikacin, including a switch from smooth to rough colony morphology, increased ability to aggregate in liquid culture, decreased motility, and increased resistance to killing by macrophages. These findings suggest the importance of using sufficient doses of antibiotics for the treatment of
M. abscessus
infections.
First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella pneumoniae Isolate
Authors: Humphries Romney M. , Yang Shangxin , Hemarajata Peera , Ward Kevin W. , Hindler Janet A. , Miller Shelley A. , Gregson Aric 
Published: July 2015

ABSTRACT

Ceftazidime-avibactam is the first antimicrobial approved by the U.S. FDA for the treatment of carbapenem-resistant
Enterobacteriaceae
. Avibactam, a non-β-lactam β-lactamase inhibitor, inactivates class A serine carbapenemases, including
Klebsiella pneumoniae
carbapenemase (KPC). We report a KPC-producing
K. pneumoniae
isolate resistant to ceftazidime-avibactam (MIC, 32/4 μg/ml) from a patient with no prior treatment with ceftazidime-avibactam.
Pharmacokinetics and Safety of Ofloxacin in Children with Drug-Resistant Tuberculosis
Authors: Garcia-Prats Anthony J. , Draper Heather R. , Thee Stephanie , Dooley Kelly E. , McIlleron Helen M. , Seddon James A. , Wiesner Lubbe , Castel Sandra , Schaaf H. Simon , Hesseling Anneke C. 
Published: July 2015

ABSTRACT

Ofloxacin is widely used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Data on its pharmacokinetics and safety in children are limited. It is not known whether the current internationally recommended pediatric dosage of 15 to 20 mg/kg of body weight achieves exposures reached in adults with tuberculosis after a standard 800-mg dose (adult median area under the concentration-time curve from 0 to 24 h [AUC
0–24
], 103 μg · h/ml). We assessed the pharmacokinetics and safety of ofloxacin in children <15 years old routinely receiving ofloxacin for MDR-TB treatment or preventive therapy. Plasma samples were collected predose and at 1, 2, 4, 8, and either 6 or 11 h after a 20-mg/kg dose. Pharmacokinetic parameters were calculated using noncompartmental analysis. Children with MDR-TB disease underwent long-term safety monitoring. Of 85 children (median age, 3.4 years), 11 (13%) were HIV infected, and of 79 children with evaluable data, 14 (18%) were underweight. The ofloxacin mean (range) maximum concentration (
C
max
), AUC
0–8
, and half-life were 8.97 μg/ml (2.47 to 14.4), 44.2 μg · h/ml (12.1 to 75.8), and 3.49 h (1.89 to 6.95), respectively. The mean AUC
0–24
, estimated in 72 participants, was 66.7 μg · h/ml (range, 18.8 to 120.7). In multivariable analysis, AUC
0–24
was increased by 1.46 μg · h/ml for each 1-kg increase in body weight (95% confidence interval [CI], 0.44 to 2.47;
P
= 0.006); no other assessed variable contributed to the model. No grade 3 or 4 events at least possibly attributed to ofloxacin were observed. Ofloxacin was safe and well tolerated in children with MDR-TB, but exposures were well below reported adult values, suggesting that dosage modification may be required to optimize MDR-TB treatment regimens in children.
Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation
Authors: Dickinson Laura , Yapa H. Manisha , Jackson Akil , Moyle Graeme , Else Laura , Amara Alieu , Khoo Saye , Back David , Karolia Zeenat , Higgs Chris , Boffito Marta 
Published: July 2015

ABSTRACT
Pharmacokinetic (PK) data describing a prolonged time course of antiretrovirals in plasma and peripheral blood mononuclear cells (PBMCs) are important for understanding and managing late or missed doses and to assess the appropriateness of compounds for preexposure prophylaxis (PrEP). This study aimed to evaluate the PK of coformulated tenofovir disoproxil fumarate (DF), emtricitabine, and rilpivirine in plasma and of the intracellular (IC) anabolites tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in healthy volunteers up to 9 days after drug cessation. Individuals received daily tenofovir DF-emtricitabine-rilpivirine (245/200/25 mg) for 14 days. Drug intake was stopped, and serial sampling occurred prior to the final dose and up to 216 h (9 days) after stopping drug intake. Concentrations were quantified and PK parameters calculated. Eighteen volunteers completed the study. The terminal elimination plasma half-lives for tenofovir and emtricitabine over 216 h (geometric mean [90% confidence interval]) were higher than those seen over 0 to 24 h (for tenofovir, 31 h [27 to 40 h] versus 13.3 h [12.5 to 15.1 h]; for emtricitabine, 41 h [36 to 54 h] versus 6.4 h (5.9 to 7.6 h]). Model-predicted IC half-lives (0 to 168 h) were 116 h (TFV-DP) and 37 h (FTC-TP). The plasma rilpivirine concentration at 216 h was 4.5 ng/ml (4.2 to 6.2 ng/ml), and half-lives over 0 to 216 h and 0 to 24 h were 47 h (41 to 59 h) and 35 h (28 to 46 h), respectively. These data contribute to our understanding of drug behavior following treatment interruption; however, adherence to therapy should be promoted. Validated plasma and IC target concentrations are necessary to allow interpretation with respect to sustained virus suppression or HIV prevention. (The trial was conducted in accordance with the Declaration of Helsinki [EudraCT 2012-002781-13].)
Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers
Authors: Molina I. , Salvador F. , Sánchez-Montalvá A. , Treviño B. , Serre N. , Sao Avilés A. , Almirante B. 
Published: July 2015

ABSTRACT

Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (
n
= 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%,
P
= 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.
Genetically Engineering Bacillus subtilis with a Heat-Resistant Arsenite Methyltransferase for Bioremediation of Arsenic-Contaminated Organic Waste
Authors: Huang Ke , Chen Chuan , Shen Qirong , Rosen Barry P. , Zhao Fang-Jie 
Published: July 2015

ABSTRACT

Organic manures may contain high levels of arsenic (As) due to the use of As-containing growth-promoting substances in animal feed. To develop a bioremediation strategy to remove As from organic waste,
Bacillus subtilis
168, a bacterial strain which can grow at high temperature but is unable to methylate and volatilize As, was genetically engineered to express the arsenite
S
-adenosylmethionine methyltransferase gene (
CmarsM
) from the thermophilic alga
Cyanidioschyzon merolae
. The genetically engineered
B. subtilis
168 converted most of the inorganic As in the medium into dimethylarsenate and trimethylarsine oxide within 48 h and volatized substantial amounts of dimethylarsine and trimethylarsine. The rate of As methylation and volatilization increased with temperature from 37 to 50°C. When inoculated into an As-contaminated organic manure composted at 50°C, the modified strain significantly enhanced As volatilization. This study provides a proof of concept of using genetically engineered microorganisms for bioremediation of As-contaminated organic waste during composting.
Bacterial Cyanuric Acid Hydrolase for Water Treatment
Authors: Yeom Sujin , Mutlu Baris R. , Aksan Alptekin , Wackett Lawrence P. 
Published: July 2015

ABSTRACT

Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from
Acidovorax citrulli
strain 12227, AtzD from
Pseudomonas
sp. strain ADP, and CAH from
Moorella thermoacetica
ATCC 39073. Each enzyme was expressed recombinantly in
Escherichia coli
and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile
M. thermoacetica
retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation.
Expression, Purification, and Biological Characterization of Babesia microti Apical Membrane Antigen 1
Authors: Moitra Prasun , Zheng Hong , Anantharaman Vivek , Banerjee Rajdeep , Takeda Kazuyo , Kozakai Yukiko , Lepore Timothy , Krause Peter J. , Aravind L. , Kumar Sanjai 
Published: July 2015

ABSTRACTThe intraerythrocytic apicomplexanBabesia microti, the primary causative agent of human babesiosis, is a major public health concern in the United States and elsewhere. Apicomplexans utilize a multiprotein complex that includes a type I membrane protein called apical membrane antigen 1 (AMA1) to invade host cells. We have isolated the full-lengthB. microtiAMA1 (BmAMA1) gene and determined its nucleotide sequence, as well as the amino acid sequence of the AMA1 protein. This protein contains an N-terminal signal sequence, an extracellular region, a transmembrane region, and a short conserved cytoplasmic tail. It shows the same domain organization as the AMA1 orthologs from piroplasm, coccidian, and haemosporidian apicomplexans but differs from all other currently known piroplasmida, including otherBabesiaandTheileriaspecies, in lacking two conserved cysteines in highly variable domain III of the extracellular region. Minimal polymorphism was detected in BmAMA1 gene sequences of parasite isolates from six babesiosis patients from Nantucket. Immunofluorescence microscopy studies showed that BmAMA1 is localized on the cell surface and cytoplasm near the apical end of the parasite. Native BmAMA1 from parasite lysate and refolded recombinant BmAMA1 (rBmAMA1) expressed inEscherichia colireacted with a mouse anti-BmAMA1 antibody using Western blotting.In vitrobinding studies showed that both native BmAMA1 and rBmAMA1 bind to human red blood cells (RBCs). This binding is trypsin and chymotrypsin treatment sensitive but neuraminidase independent. Incubation ofB. microtiparasites in human RBCs with a mouse anti-BmAMA1 antibody inhibited parasite growth by 80% in a 24-h assay. Based on its antigenically conserved nature and potential role in RBC invasion, BmAMA1 should be evaluated as a vaccine candidate.