bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streptomycin-Starved Mycobacterium tuberculosis 18b, a Drug Discovery Tool for Latent Tuberculosis
Authors: Zhang Ming , Sala Claudia , Hartkoorn Ruben C. , Dhar Neeraj , Mendoza-Losana Alfonso , Cole Stewart T. 
Published: August 2012

ABSTRACT

Mycobacterium tuberculosis
18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-starved 18b (SS18b) model both
in vitro
and
in vivo
by comparing the behavior of 22 approved and experimental tuberculosis drugs. Using the resazurin reduction microplate assay (REMA), rifampin (RIF), rifapentine (RPT), TMC207, clofazimine (CFM), and linezolid (LIN) were found to be active against SS18b
in vitro
, and their bactericidal activity was confirmed by determining the number of CFU. A latent 18b infection was established in mice, and some of the above-mentioned drugs were used for treatment, either alone or in combination with RIF. RIF, RPT, TMC207, CFM, and pyrazinamide (PZA) were all active
in vivo
, while cell wall inhibitors were not. A comparative kinetic study of rifamycin efficacy was then undertaken, and the results indicated that RPT clears latent 18b infection in mice faster than RIF. Intrigued by the opposing responses of live and dormant 18b cells to cell wall inhibitors, we conducted a systematic analysis of 14 such inhibitors using REMA. This uncovered an SS18b signature (CWPRED) that accurately predicted the activities of cell wall inhibitors and performed well in a blind study. CWPRED will be useful for establishing the mode of action of compounds with unknown targets, while the SS18b system should facilitate the discovery of drugs for treating latent tuberculosis.
pEl1573 Carrying
bla
IMP-4
, from Sydney, Australia, Is Closely Related to Other IncL/M Plasmids
Authors: Partridge Sally R. , Ginn Andrew N. , Paulsen Ian T. , Iredell Jonathan R. 
Published: August 2012

ABSTRACT

Complete sequencing of pEl1573, a representative IncL/M plasmid carrying
bla
IMP-4
from Sydney, Australia, revealed an ∼60-kb backbone almost identical to those of IncL/M plasmids pCTX-M3, from Poland, and pCTX-M360, from China, and less closely related to pNDM-HK, pOXA-48a, and pEL60, suggesting different lineages. The ∼28-kb Tn
2
-derived multiresistance region in pEl1573 is inserted in the same location as those in pCTX-M3 and pNDM-HK and shares some of the same components but has undergone rearrangements.
Activity of Gallidermin on Staphylococcus aureus and Staphylococcus epidermidis Biofilms
Authors: Saising Jongkon , Dube Linda , Ziebandt Anne-Kathrin , Voravuthikunchai Supayang Piyawan , Nega Mulugeta , Götz Friedrich 
Published: August 2012

ABSTRACT

Due to their abilities to form strong biofilms,
Staphylococcus aureus
and
Staphylococcus epidermidis
are the most frequently isolated pathogens in persistent and chronic implant-associated infections. As biofilm-embedded bacteria are more resistant to antibiotics and the immune system, they are extremely difficult to treat. Therefore, biofilm-active antibiotics are a major challenge. Here we investigated the effect of the lantibiotic gallidermin on two representative biofilm-forming staphylococcal species. Gallidermin inhibits not only the growth of staphylococci in a dose-dependent manner but also efficiently prevents biofilm formation by both species. The effect on biofilm might be due to repression of biofilm-related targets, such as
ica
(intercellular adhesin) and
atl
(major autolysin). However, gallidermin's killing activity on 24-h and 5-day-old biofilms was significantly decreased. A subpopulation of 0.1 to 1.0% of cells survived, comprising “persister” cells of an unknown genetic and physiological state. Like many other antibiotics, gallidermin showed only limited activity on cells within mature biofilms.
In Vitro
Combination Studies of Benzothiazinone Lead Compound BTZ043 against Mycobacterium tuberculosis
Authors: Lechartier Benoit , Hartkoorn Ruben C. , Cole Stewart T. 
Published: August 2012

ABSTRACT

Benzothiazinones (BTZ) are a new class of drug candidates to combat tuberculosis that inhibit decaprenyl-phosphoribose epimerase (DprE1), an essential enzyme involved in arabinan biosynthesis. Using the checkerboard method and cell viability assays, we have studied the interaction profiles of BTZ043, the current lead compound, with several antituberculosis drugs or drug candidates against
Mycobacterium tuberculosis
strain H37Rv, namely, rifampin, isoniazid, ethambutol, TMC207, PA-824, moxifloxacin, meropenem with or without clavulanate, and SQ-109. No antagonism was found between BTZ043 and the tested compounds, and most of the interactions were purely additive. Data from two different approaches clearly indicate that BTZ043 acts synergistically with TMC207, with a fractional inhibitory concentration index of 0.5. TMC207 at a quarter of the MIC (20 ng/ml) used in combination with BTZ043 (1/4 MIC, 0.375 ng/ml) had a stronger bactericidal effect on
M. tuberculosis
than TMC207 alone at a concentration of 80 ng/ml. This synergy was not observed when the combination was tested on a BTZ-resistant
M. tuberculosis
mutant, suggesting that DprE1 inhibition is the basis for the interaction. This finding excludes the possibility of synergy occurring through an off-target mechanism. We therefore hypothesize that sub-MICs of BTZ043 weaken the bacterial cell wall and allow improved penetration of TMC207 to its target. Synergy between two new antimycobacterial compounds, such as TMC207 and BTZ043, with novel targets, offers an attractive foundation for a new tuberculosis regimen.
The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc
Authors: Sobke A. , Klinger M. , Hermann B. , Sachse S. , Nietzsche S. , Makarewicz O. , Keller P. M. , Pfister W. , Straube E. 
Published: August 2012

ABSTRACT

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in
Pseudomonas aeruginosa
, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity.
Comparative Transcriptomic and Proteomic Analyses of Trichomonas vaginalis following Adherence to Fibronectin
Authors: Huang Kuo-Yang , Huang Po-Jung , Ku Fu-Man , Lin Rose , Alderete John F. , Tang Petrus 
Published: August 2012

ABSTRACT

The morphological transformation of
Trichomonas vaginalis
from an ellipsoid form in batch culture to an adherent amoeboid form results from the contact of parasites with vaginal epithelial cells and with immobilized fibronectin (FN), a basement membrane component. This suggests host signaling of the parasite. We applied integrated transcriptomic and proteomic approaches to investigate the molecular responses of
T. vaginalis
upon binding to FN. A transcriptome analysis was performed by using large-scale expressed-sequence-tag (EST) sequencing. A total of 20,704 ESTs generated from batch culture (trophozoite-EST) versus FN-amoeboid trichomonad (FN-EST) cDNA libraries were analyzed. The FN-EST library revealed decreased amounts of transcripts that were of lower abundance in the trophozoite-EST library. There was a shift by FN-bound organisms to the expression of transcripts encoding essential proteins, possibly indicating the expression of genes for adaptation to the morphological changes needed for the FN-adhesive processes. In addition, we identified 43 differentially expressed proteins in the proteomes of FN-bound and unbound trichomonads. Among these proteins, cysteine peptidase, glyceraldehyde-3-phosphate dehydrogenase (an FN-binding protein), and stress-related proteins were upregulated in the FN-adherent cells. Stress-related genes and proteins were highly expressed in both the transcriptome and proteome of FN-bound organisms, implying that these genes and proteins may play critical roles in the response to adherence. This is the first report of a comparative proteomic and transcriptomic analysis after the binding of
T. vaginalis
to FN. This approach may lead to the discovery of novel virulence genes and affirm the role of genes involved in disease pathogenesis. This knowledge will permit a greater understanding of the complex host-parasite interplay.
Neutrophil Extracellular Traps Exhibit Antibacterial Activity against Burkholderia pseudomallei and Are Influenced by Bacterial and Host Factors
Authors: Riyapa Donporn , Buddhisa Surachat , Korbsrisate Sunee , Cuccui Jon , Wren Brendan W. , Stevens Mark P. , Ato Manabu , Lertmemongkolchai Ganjana 
Published: August 2012

ABSTRACT

Burkholderia pseudomallei
is the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. Polymorphonuclear neutrophils (PMNs) kill microbes extracellularly by the release of neutrophil extracellular traps (NETs). PMNs play a key role in the control of melioidosis, but the involvement of NETs in killing of
B. pseudomallei
remains obscure. Here, we showed that bactericidal NETs were released from human PMNs in response to
B. pseudomallei
in a dose- and time-dependent manner.
B. pseudomallei
-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways.
B. pseudomallei
mutants defective in the virulence-associated Bsa type III protein secretion system (T3SS) or capsular polysaccharide I (CPS-I) induced elevated levels of NETs. NET induction by such mutants was associated with increased bacterial killing, phagocytosis, and oxidative burst by PMNs. Taken together the data imply that T3SS and the capsule may play a role in evading the induction of NETs. Importantly, PMNs from diabetic subjects released NETs at a lower level than PMNs from healthy subjects. Modulation of NET formation may therefore be associated with the pathogenesis and control of melioidosis.
Genome Sequence of Staphylococcus equorum subsp. equorum Mu2, Isolated from a French Smear-Ripened Cheese
Authors: Irlinger Françoise , Loux Valentin , Bento Pascal , Gibrat Jean-François , Straub Cécile , Bonnarme Pascal , Landaud Sophie , Monnet Christophe 
Published: August 2012

ABSTRACTStaphylococcus equorumsubsp.equorumis a member of the coagulase-negative staphylococcus group and is frequently isolated from fermented food products and from food-processing environments. It contributes to the formation of aroma compounds during the ripening of fermented foods, especially cheeses and sausages. Here, we report the draft genome sequence ofStaphylococcus equorumsubsp.equorumMu2 to provide insights into its physiology and compare it with otherStaphylococcusspecies.
Draft Genome Sequence of Actinomyces massiliensis Strain 4401292T
Authors: Roux Véronique , Robert Catherine , Gimenez Grégory , Gharbi Reem , Raoult Didier 
Published: August 2012

ABSTRACTA draft genome sequence ofActinomyces massiliensis, an anaerobic bacterium isolated from a patient's blood culture, is described here. CRISPR-associated proteins, insertion sequences, and toxin-antitoxin loci were found on the genome.
Whole-Genome Sequences and Comparative Genomics of Salmonella enterica Serovar Typhi Isolates from Patients with Fatal and Nonfatal Typhoid Fever in Papua New Guinea
Authors: Baddam Ramani , Thong Kwai-Lin , Avasthi Tiruvayipati Suma , Shaik Sabiha , Yap Kien-Pong , Teh Cindy Shuan Ju , Chai Lay-Ching , Kumar Narender , Ahmed Niyaz 
Published: August 2012

ABSTRACTMany of the developing countries of the Southeast Asian region are significantly affected by endemic typhoid fever, possibly as a result of marginal living standards. It is an important public health problem in countries such as Papua New Guinea, which is geographically close to some of the foci of endemicity in Asia. The severity of the disease varies in different regions, and this may be attributable to genetic diversity among the native strains. Genome sequence data on strains from different countries are needed to clearly understand their genetic makeup and virulence potential. We describe the genomes of twoSalmonellaTyphi isolates from patients with fatal and nonfatal cases of typhoid fever in Papua New Guinea. We discuss in brief the underlying sequencing methodology, assembly, genome statistics, and important features of the two draft genomes, which form an essential step in our functional molecular infection epidemiology program centering on typhoid fever. The comparative genomics of these and other isolates would enable us to identify genetic rearrangements and mechanisms responsible for endemicity and the differential severity of pathogenic salmonellae in Papua New Guinea and elsewhere.
Insights from the Genome Sequence of a Salmonella enterica Serovar Typhi Strain Associated with a Sporadic Case of Typhoid Fever in Malaysia
Authors: Yap Kien-Pong , Teh Cindy Shuan Ju , Baddam Ramani , Chai Lay-Ching , Kumar Narender , Avasthi Tiruvayipati Suma , Ahmed Niyaz , Thong Kwai-Lin 
Published: August 2012

ABSTRACTSalmonella entericaserovar Typhi is the causative agent of typhoid fever, which causes nearly 21.7 million illnesses and 217,000 deaths globally. Herein, we describe the whole-genome sequence of theSalmonellaTyphi strain ST0208, isolated from a sporadic case of typhoid fever in Kuala Lumpur, Malaysia. The whole-genome sequence and comparative genomics allow an in-depth understanding of the genetic diversity, and its link to pathogenicity and evolutionary dynamics, of this highly clonal pathogen that is endemic to Malaysia.
Genome Analysis of Mycobacterium massiliense Strain M172, Which Contains a Putative Mycobacteriophage
Authors: Choo Siew Woh , Yusoff Aini Mohamed , Wong Yan Ling , Wee Wei Yee , Ong Chia Sui , Ng Kee Peng , Ngeow Yun Fong 
Published: August 2012

ABSTRACTThe genome ofMycobacterium massilienseM172, isolated from a human sputum sample, was sequenced using Illumina GA IIX technology and found to contain 5,204,460 bp, including putative genes for virulence and antibiotic resistance as well as a 92-kb genomic region most likely to correspond to a mycobacteriophage.
Draft Genome Sequences for Two Metal-Reducing Pelosinus fermentans Strains Isolated from a Cr(VI)-Contaminated Site and for Type Strain R7
Authors: Brown Steven D. , Podar Mircea , Klingeman Dawn M. , Johnson Courtney M. , Yang Zamin K. , Utturkar Sagar M. , Land Miriam L. , Mosher Jennifer J. , Hurt Richard A. , Phelps Tommy J. , Palumbo Anthony V. , Arkin Adam P. , Hazen Terry C. , Elias Dwayne A. 
Published: August 2012

ABSTRACTPelosinus fermentans16S rRNA gene sequences have been reported from diverse geographical sites since the recent isolation of the type strain. We present the genome sequence of theP. fermentanstype strain R7 (DSM 17108) and genome sequences for two new strains with different abilities to reduce iron, chromate, and uranium.
A report of an outbreak of toxicity from a novel drug of abuse: ERIC-3
Authors: Haig Stephen Douglas , Kelly Charlotte , Morden Clare 
Published: August 2012

BackgroundNovel drugs of abuse are becoming more common in the UK, and they represent particular difficulties in management. We present a case series of toxicity due to a novel substance Eric-3.MethodsThis was a retrospective case note review over a 6-month period. Patients were included if their presentation was due to ingestion of Eric-3. Physiological data, symptoms, outcome and destination of the patient from the ED were collected. Postmortem toxicological analysis was obtained for one of the patients who died.Results41 attendances were identified from 18 patients. Two patients died and five were admitted to ITU. Heart rate and temperature on arrival tended to be above normal (mean heart rate was 112 bpm, with an SD of 18; mean temperature was 37.45° with an SD of 0.95°). 63.4% of attendances included agitation and 34.1% choreiform movements. α-Methyltryptamine and 3-/4-flouroephedrine were found in the blood of one of the patients who died.ConclusionsIn this outbreak, Eric-3 gave symptoms similar to other stimulants. It may have been a novel substance 3-/4-flouroephedrine. It underlines the need for prospective data collection and information sharing.
Detection ofhssS,hssR,hrtA, andhrtBgenes and their expression by hemin inStaphylococcus epidermidis
Authors: Juárez-Verdayes Marco A. , González-Uribe Pilar M. , Peralta Humberto , Rodríguez-Martínez Sandra , Jan-Roblero Janet , Escamilla-Hernández Rosalba , Cancino-Diaz Mario E. , Cancino-Diaz Juan C. 
Published: August 2012

Staphylococcus aureus employs a heme sensing system (HssR–HssS) and a heme-regulated transporter efflux pump (HrtA–HrtB) to avoid the accumulation of heme, which is toxic at high concentrations. The detoxification system to heme has not been studied in Staphylococcus epidermidis . In this work, the hssR, hssS, hrtA, and hrtB genes were detected, and their expression when stimulated by hemin in S. epidermidis was explored. In silico genomic analyses exhibited that the genetic organization of the hssRS and hrtAB genes was identical in 11 Staphylococcus species analyzed, including S. epidermidis. Slight variations were found in their syntenic regions. The predicted secondary structure of HrtAB proteins from these species was almost identical to these of S. aureus. Additionally, hrtAB promoter sequences of some species were analyzed, and 1 or 2 different nucleotide substitutions were found in the downstream motif. Concentrations of hemin above 5 µmol/L inhibited S. epidermidis growth. However, S. epidermidis that was pre-exposed to a subinhibitory hemin concentration (1 µmol/L) was able to grow when inoculated into medium containing above 5 µmol/L hemin. The expression levels of hrtA and hrtB genes in S. epidermidis exhibited a significant difference when they were stimulated with hemin. Our results suggest that the HrtAB could be involved in hemin detoxification of S. epidermidis.
RIGID CONTAINMENT WALLS FOR LIQUEFACTION REMEDIATION
Authors: MITRANI HELEN , MADABHUSHI S. P. G. 
Published: August 2012

Many typical ground improvement techniques that are used for liquefaction remediation, such as in situ densification, are not appropriate for application under existing buildings and more novel techniques are required. This paper describes centrifuge tests investigating the performance of rigid containment walls as a liquefaction remediation method. A simple frame structure, founded on a deep layer of loose, liquefiable sand was tested under earthquake shaking. Centrifuge tests were then carried out with containment walls around the base of the structure, extending through the full depth of the liquefiable layer and also partial depth. It is found that rigid containment walls can be very effective in reducing structural settlements primarily by preventing lateral movement of the foundation sand but the impermeability of the walls may also be important. Improvements in structural settlement are observed even when the walls do not extend through the full depth of the liquefiable layer, if the depth of the walls is greater than the depth of the free field liquefaction. In addition, it is found that the accelerations of the structure are not increased, provided there is no rigid, structural connection between the structure and the containment walls.
Incremental research vs. paradigm-shift mania
Authors: Meyer Bertrand 
Published: August 2012

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Leptin and Soluble Leptin Receptor in Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
Authors: Aleksandrova Krasimira , Boeing Heiner , Jenab Mazda , Bueno-de-Mesquita H. Bas , Jansen Eugene , van Duijnhoven Fränzel J. B. , Rinaldi Sabina , Fedirko Veronika , Romieu Isabelle , Riboli Elio , Gunter Marc J. , Westphal Sabine , Overvad Kim , Tjønneland Anne , Halkjær Jytte , Racine Antoine , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Kaaks Rudolf , Lukanova Annekatrin , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Mattiello Amalia , Pala Valeria , Palli Domenico , Tumino Rosario , Vineis Paolo , Buckland Genevieve , Sánchez María-José , Amiano Pilar , Huerta José María , Barricarte Aurelio , Menéndez Virginia , Peeters Petra H. , Söderberg Stefan , Palmqvist Richard , Allen Naomi E. , Crowe Francesca L. , Khaw Kay-Tee , Wareham Nickolas , Pischon Tobias 
Published: August 2012

Abstract
Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40–0.76; Ptrend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28–0.63, Ptrend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48–1.44, Ptrend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56–1.29, Ptrend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328–37. ©2012 AACR.