bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Novel Transposon (Tn
6072
) and a Truncated Staphylococcal Cassette Chromosome
mec
Element in Methicillin-Resistant
Staphylococcus aureus
ST239
Authors: Chen Liang , Mediavilla José R. , Smyth Davida S. , Chavda Kalyan D. , Ionescu Ramona , Roberts Richard B. , Robinson D. Ashley , Kreiswirth Barry N. 
Published: May 2010

ABSTRACT

A novel composite transposon (Tn
6072
) resembling staphylococcal cassette chromosome
mercury
(SCC
Hg
) was identified in a collection of sequence type (ST) 239 methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) isolates from Romanian hospitals. Tn
6072
is homologous to the 5′ region of SCC
Hg
found in staphylococcal cassette chromosome
mec
(SCC
mec
) type III prototype strain 85/2082 but lacks the characteristic
mer
operon. SCC
Hg
has previously been reported to integrate downstream of
orfX
, at the same chromosomal location as SCC
mec
. Tn
6072
, by contrast, is demarcated by two IS
431
elements, flanked by 8-bp direct repeats, and inserted upstream of the origin of replication, within an open reading frame homologous to SAR2700 of
S. aureus
strain MRSA252. Analysis of a geographically and temporally diverse collection of 111 strains from the ST239 clonal group uncovered 11 additional strains harboring Tn
6072
, demonstrating a lineage-specific insertion pattern. Complete sequence analysis of the SCC
mec
regions of two representative Romanian strains (BK16704, BK16691) revealed two additional novel structures derived from a type III SCC
mec
background. BK16704 possesses an SCC
mec
3A.1.4 structure, with an IS
256
insertion downstream of the right chromosomal junction. In contrast, the SCC
mec
element of BK16691 is truncated downstream of the
mec
gene complex, with a 24-kb deletion encompassing the right chromosomal junction and an inverted downstream IS
256
element. This structure, tentatively named “ψSCC
mec
16691
,” confers methicillin resistance but lacks most of the J1/J2 region, including the
ccr
gene complex. Taken together, these findings provide evidence for the continuing evolution of SCC elements, as well as the ST239 clonal group.
In Vitro
and
In Vivo
Activities of Arachidonic Acid against
Schistosoma mansoni
and
Schistosoma haematobium
Authors: El Ridi Rashika , Aboueldahab Marwa , Tallima Hatem , Salah Mohamed , Mahana Noha , Fawzi Samia , Mohamed Shadia H. , Fahmy Omar M. 
Published: May 2010

ABSTRACT

The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old
Schistosoma mansoni
and 9-, 10-, and 12-week-old
Schistosoma haematobium
worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl
2
and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated
S. mansoni
and
S. haematobium
worm attrition was reproduced
in vivo
in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy.
A Novel Polymyxin Derivative That Lacks the Fatty Acid Tail and Carries Only Three Positive Charges Has Strong Synergism with Agents Excluded by the Intact Outer Membrane
Authors: Vaara Martti , Siikanen Osmo , Apajalahti Juha , Fox John , Frimodt-Møller Niels , He Hui , Poudyal Anima , Li Jian , Nation Roger L. , Vaara Timo 
Published: May 2010

ABSTRACTPolymyxins are cationic lipopeptides (five cationic charges) and the last resort for the treatment of serious Gram-negative infections caused by multiresistant strains. NAB741 has a cyclic peptide portion identical to that of polymyxin B but carries in the linear peptide portion a threonyl-d-serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). At the N terminus of the peptide, NAB741 carries an acetyl group instead of a mixture of methyl octanoyl and methyl heptanoyl residues. NAB741 sensitizedEscherichia coli,Klebsiella pneumoniae,Enterobacter cloacae, andAcinetobacter baumanniito antibiotics against which the intact outer membrane is an effective permeability barrier. When tested by using Etest strips on plates containing increasing concentrations of NAB741, the fractional inhibition concentration index (FICI) of the combination of NAB741 with rifampin ranged from ≤0.111 to 0.158 and that with clarithromycin from ≤0.094 to 0.292. When tested by the checkerboard method, the corresponding FICI values againstE. coliATCC 25922 were ≤0.141 to ≤0.155 with rifampin and 0.094 with clarithromycin. In addition, at 4 μg/ml, NAB741 decreased the MICs of azithromycin, mupirocin, fusidic acid, and vancomycin forE. colistrains andE. cloacaeby factors ranging from 8 to 200. A sister peptide, NAB752, carrying a threonyl-aminobutyryl residue as the linear peptide portion, was inactive. Furthermore, NAB741 sensitizedE. colito the bactericidal activity of fresh guinea pig serum. The renal clearance of NAB741 was approximately 400-fold, 16-fold, and 8-fold higher than those measured for colistin, NAB7061, and NAB739, respectively.
Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration
Authors: Bilgrami I. , Roberts J. A. , Wallis S. C. , Thomas J. , Davis J. , Fowler S. , Goldrick P. B. , Lipman J. 
Published: May 2010

ABSTRACT

Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. The objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume CVVHF with high-volume exchanges (≥4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] every 8 h) are sufficient for treatment of less susceptible organisms such as
Burkholderia pseudomallei
(MIC, 4 mg/liter); and, finally, to compare the clearances observed in this study with data from previous studies using lower-volume exchanges (1 to 2 liters/h). We recruited 10 eligible patients and collected serial pre- and postfilter blood samples and ultrafiltrate and urine samples. A noncompartmental method was used to determine meropenem pharmacokinetics. The cohort had a median age of 56.6 years, a median weight of 70 kg, and a median APACHE II (acute physiology and chronic health evaluation) score of 25. The median (interquartile range) values for meropenem were as follows: terminal elimination half-life, 4.3 h (2.9 to 6.0); terminal volume of distribution, 0.2 liters/kg (0.2 to 0.3); trough concentration, 7.7 mg/liter (6.2 to 12.9); total clearance, 6.0 liters/h (5.2 to 6.2); hemofiltration clearance, 3.5 liters/h (3.4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (
R
2
= 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as
B. pseudomallei
.
First Detection of CTX-M and SHV Extended-Spectrum β-Lactamases in
Escherichia coli
Urinary Tract Isolates from Dogs and Cats in the United States
Authors: O'Keefe Alexandra , Hutton Tabitha A. , Schifferli Dieter M. , Rankin Shelley C. 
Published: May 2010

ABSTRACT

One hundred fifty canine and feline
Escherichia coli
isolates associated with urinary tract infections were screened for the presence of extended-spectrum β-lactamase (ESBL) genes. Out of 60 isolates suspected to be ESBL positive based on antimicrobial susceptibility testing, 11 ESBLs were identified, including one SHV-12 gene, one CTX-M-14 gene, and nine CTX-M-15 genes. This study provides the first report of CTX-M- and SHV-type ESBLs in dogs and cats in the United States.
Cysteamine, the Molecule Used To Treat Cystinosis, Potentiates the Antimalarial Efficacy of Artemisinin
Authors: Min-Oo Gundula , Fortin Anny , Poulin Jean-François , Gros Philippe 
Published: May 2010

ABSTRACTMalaria continues to be a major threat to global health. Artemisinin combination therapy (ACT) is the recommended treatment for clinical malaria; however, recent reports of parasite resistance to artemisinin in certain areas where malaria is endemic have stressed the need for developing more efficacious ACT. We report that cysteamine (Cys), the aminothiol used to treat nephropathic cystinosis in humans, strongly potentiates the efficacy of artemisinin against thePlasmodiumparasitein vivo. Using a mouse model of infection withPlasmodium chabaudiAS, we observe that Cys dosing used to treat cystinosis in humans can strongly potentiate (by 3- to 4-fold) the antimalarial properties of the artemisinin derivatives artesunate and dihydroartemisinin. Addition of Cys to suboptimal doses of artemisinin delays the appearance of blood parasitemia, strongly reduces the extent of parasite replication, and significantly improves survival in a model of lethalP. chabaudiinfection. Cys, the natural product of the enzyme pantetheinase, has a history of safe use for the clinical management of cystinosis. Our findings suggest that Cys could be included in novel ACTs to improve efficacy againstPlasmodiumparasite replication, including artemisinin-resistant isolates. Future work will include clinical evaluation of novel Cys-containing ACTs and elucidation of the mechanism underlying the potentiation effect of Cys.
Effect on Human Cells of Environmental
Vibrio parahaemolyticus
Strains Carrying Type III Secretion System 2
Authors: Caburlotto Greta , Lleò Maria M. , Hilton Tamara , Huq Anwar , Colwell Rita R. , Kaper James B. 
Published: May 2010

ABSTRACT

Vibrio parahaemolyticus
is an inhabitant of estuarine and marine environments that causes seafood-borne gastroenteritis worldwide. Recently, a type 3 secretion system (T3SS2) able to secrete and translocate virulence factors into the eukaryotic cell has been identified in a pathogenicity island (VP-PAI) located on the smaller chromosome. These virulence-related genes have previously been detected only in clinical strains. Classical virulence genes for this species (
tdh
,
trh
) are rarely detected in environmental strains, which are usually considered to lack virulence potential. However, during screening of a collection of environmental
V. parahaemolyticus
isolates obtained in the North Adriatic Sea in Italy, a number of marine strains carrying virulence-related genes, including genes involved in the T3SS2, were detected. In this study, we investigated the pathogenic potential of these marine
V. parahaemolyticus
strains by studying their adherence ability, their cytotoxicity, their effect on zonula occludin protein 1 (ZO-1) of the tight junctions, and their effect on transepithelial resistance (TER) in infected Caco-2 cells. By performing a reverse transcription-PCR, we also tested the expression of the T3SS2 genes
vopT
and
vopB2
, encoding an effector and a translocon protein, respectively. Our results indicate that, similarly to clinical strains, marine
V. parahaemolyticus
strains carrying
vopT
and
vopB2
and that other genes included in the VP-PAI are capable of adhering to human cells and of causing cytoskeletal disruption and loss of membrane integrity in infected cells. On the basis of data presented here, environmental
V. parahaemolyticus
strains should be included in coastal water surveillance plans, as they may represent a risk for human health.
Intramolecular Interactions between the Protease and Structural Domains Are Important for the Functions of Serine Protease Autotransporters
Authors: Tsang Casey , Malik Huma , Nassman Deana , Huang Antony , Tariq Fayha , Oelschlaeger Peter , Stathopoulos Christos 
Published: May 2010

ABSTRACT

Autotransporter (AT) is a protein secretion pathway found in Gram-negative bacteria featuring a multidomain polypeptide with a signal sequence, a passenger domain, and a translocator domain. An AT subfamily named serine protease ATs of the family
Enterobacteriaceae
(SPATEs) is characterized by the presence of a conserved serine protease motif in the passenger domain which contributes to bacterial pathogenesis. The goal of the current study is to determine the importance of the passenger domain conserved residues in the SPATE proteolytic and adhesive functions using the temperature-sensitive hemagglutinin (Tsh) protein as our model. To begin, mutations of 21 fully conserved residues in the four passenger domain conserved motifs were constructed by PCR-based site-directed mutagenesis. Seventeen mutants exhibited a wild-type secretion level; among these mutants, eight displayed reduced proteolytic activities in Tsh-specific oligopeptide and mucin cleavage assays. These eight mutants also demonstrated lower affinities to extracellular matrix proteins, collagen IV, and fibronectin. These eight conserved residues were analyzed by molecular graphics modeling to demonstrate their intramolecular interactions with the catalytic triad and other key residues. Additional mutations were made to confirm the above interactions in order to demonstrate their significance to the SPATE functions. Altogether our data suggest that certain conserved residues in the SPATE passenger domain are important for both the proteolytic and adhesive activities of SPATE by maintaining the proper protein structure via intramolecular interactions between the protease and β-helical domains. Here, we provide new insight into the structure-function relationship of the SPATEs and the functional roles of their conserved residues.
Staphylococcal Superantigen-Like Protein 5 Inhibits Matrix Metalloproteinase 9 from Human Neutrophils
Authors: Itoh Saotomo , Hamada Eri , Kamoshida Go , Takeshita Kana , Oku Teruaki , Tsuji Tsutomu 
Published: May 2010

ABSTRACTStaphylococcal superantigen-like proteins (SSLs) constitute a family of exoproteins exhibiting structural similarities to superantigens and enterotoxins but no superantigenic activity. In this article, we present evidence that SSL5 specifically binds to matrix metalloproteinase 9 (MMP-9) and inhibits its enzymatic activity. When human neutrophil cell lysate was applied to recombinant His-tagged SSL5 conjugated to Sepharose, the bound fraction gave a major band of approximately 100 kDa in SDS-polyacrylamide gel electrophoresis. This protein was identified as the proform of MMP-9 (proMMP-9) by peptide mass fingerprinting analysis. The recombinant SSL5-Sepharose also bound to proMMP-9 secreted by interleukin 8 (IL-8)-stimulated neutrophils and HT1080 fibrosarcoma cells. Surface plasmon resonance analysis revealed that recombinant SSL5 bound to proMMP-9 with rather high affinity (dissociation constant [KD] = 1.9 nM). Recombinant SSL5 was found to effectively inhibit MMP-9-catalyzed hydrolysis of gelatin and a synthetic fluorogenic peptide in a noncompetitive manner (Ki= 0.097 nM), as assessed by zymography and the fluorescence quenching method. Finally, the transmigration of neutrophils across Matrigel basement membranes in response toN-formyl-methionyl-leucyl-phenylalanine (FMLP) was suppressed by the presence of recombinant SSL5. We discuss possible roles that SSL5 may play in immune evasion of staphylococci by inhibiting MMP and interfering with leukocyte trafficking.
The
Staphylococcus aureus
Epidermal Cell Differentiation Inhibitor Toxin Promotes Formation of Infection Foci in a Mouse Model of Bacteremia
Authors: Munro Patrick , Benchetrit Maxime , Nahori Marie-Anne , Stefani Caroline , Clément René , Michiels Jean-François , Landraud Luce , Dussurget Olivier , Lemichez Emmanuel 
Published: May 2010

ABSTRACT

Inactivation of the host GTPase RhoA by staphylococcal epidermal cell differentiation inhibitor (EDIN) exotoxins triggers the formation of large transcellular tunnels, named macroapertures, in endothelial cells. We used bioluminescent strains of
Staphylococcus aureus
to monitor the formation of infection foci during the first 24 h of hematogenous bacterial dissemination. Clinically derived EDIN-expressing
S. aureus
strains S25 and Xen36 produced many disseminated foci. EDIN had no detectable impact on infection foci in terms of histopathology or the intensity of emitted light. Moreover, EDIN did not modify the course of bacterial clearance from the bloodstream. In contrast, we show that EDIN expression promotes a 5-fold increase in the number of infection foci produced by Xen36. This virulence activity of EDIN requires RhoA ADP-ribosyltranferase activity. These results suggest that EDIN is a risk factor for
S. aureus
dissemination through the vasculature by virtue of its ability to promote the formation of infection foci in deep-seated tissues.
The Oligosaccharide of Gonococcal Lipooligosaccharide Contains Several Epitopes That Are Recognized by Human Antibodies
Authors: Yamasaki Ryohei , Yabe Uichirou , Kataoka Chikako , Takeda Ushio , Asuka Shunpei 
Published: May 2010

ABSTRACT

Recently, we isolated human IgG from normal human sera (NHS) using lipooligosaccharide (LOS) from gonococcal strain JW31R as an affinity ligand. We provided evidence that the oligosaccharide (OS) moiety of LOS was immunogenic in humans and that NHS contains functional antibodies that bind to the branched OS. The present study aimed to identify bactericidal antibodies that bind to partial core OS structures or their adjacent sites expressed in the 3,4-branched and 2,3:3,4-dibranched neisserial LOSs. Using 15253 LOS from serum-resistant gonococcal strain 15253 as an affinity ligand, we isolated IgG2 and found that this preparation contained at least three different species. (i) One IgG2 species recognized a cross-reactive epitope that is expressed on 3,4-branched and 2,3:3,4-dibranched neisserial LOSs. (ii) Another IgG2 species was specific for JW31R LOS from a pyocin-resistant gonococcal strain; this IgG-defined epitope was not shared with the aforementioned branched LOSs. (iii) The third IgG2 species bound to the “
Salmonella
minnesota
” Rb and Re mutant lipopolysaccharides (LPSs); this IgG2 recognizes a KDOα2-4KDO residue at the reducing end of the carbohydrate moiety of each LPS. The IgG2 was also found to be functional and facilitated the killing of strain 15253. The current results show that neisserial LOS contains several epitopes within its OS moiety that are recognized by human antibodies.
ESR analysis of the oxidation reactions of phosphorus-containing nitrone-type spin traps with gold(III) ion
Authors: Nakajima Akira , Matsuda Emiko , Ueda Yuto , Tajima Kunihiko 
Published: May 2010

Phosphorus-containing cyclic nitrones, such as DEPMPO, CYPMPO, and DPPMPO, were oxidized by hydrogen tetrachloroaurate(III) to DEPMPOX, CYPMPOX, and DPPMPOX with the precipitation of Au(0). The reaction was depressed by the addition of chloride or hydroxide ions. The peculiar pH dependency was observed in DEPMPOX, CYPMPOX, and DPPMPOX formation, which should be caused by the diethoxyphosphoryl group in DEPMPO, the 1,3-propoxy cyclophosphoryl group in CYPMPO, and the diphenylphosphinoyl group in DPPMPO. The oxidation of the nitrones proceeded through the ligand exchange of Cl– in AuCl4– with >N+–O– in nitrone and the nucleophilic addition of the water molecule to the C-2 position in the nitrones, the stepwise intra-molecular transfer of three electrons from the nitrones to Au(III), and the release of the resulting Au(0). The phosphoryl group in the nitrones suppressed the first ligand-exchange interaction by its electronegativity, while the group promoted the electron transfer from the nitrones to Au(III) by its inductive effect.
Redox reactions of reactive oxygen species in aqueous solutions as the probe for scanning electrochemical microscopy of single live T24 cells
Authors: Zhao Xiaocui , Zhang Mengni , Long Yitao , Ding Zhifeng 
Published: May 2010

The redox reactions of two main components of reactive oxygen species (ROS), superoxide and hydrogen peroxide, along with oxygen in aqueous solutions were investigated using a conventional electrochemical technique, differential pulse voltammetry (DPV). Superoxide undergoes oxidation at a Pt working electrode biased at 0.055 V versus Ag/AgCl, while hydrogen peroxide can be oxidized and reduced at 0.817 and –0.745 V, respectively. Oxygen in the solutions is reduced at the electrode with an applied potential of –0.455 V. Based on these results, hydrogen peroxide and superoxide released from live cells can be successfully monitored, identified, and mapped using scanning electrochemical microscopy (SECM) at different potentials. Single human bladder (T24) cells were imaged using a 5 μm diameter SECM probe biased at –0.400, –0.600, and –0.800 V. Oxygen reduction that seems an interference can be discriminated from that of hydrogen peroxide by means of SECM.
UNITARIES IN A SIMPLE C*-ALGEBRA OF TRACIAL RANK ONE
Authors: LIN HUAXIN 
Published: May 2010

Let A be a unital separable simple infinite dimensional C*-algebra with tracial rank not more than one and with the tracial state space T(A) and let U(A) be the unitary group of A. Suppose that u ∈ U0(A), the connected component of U(A) containing the identity. We show that, for any ϵ > 0, there exists a self-adjoint element h ∈ As.a such that [Formula: see text] We also study the problem when u can be approximated by unitaries in A with finite spectrum. Denote by CU(A) the closure of the subgroup of unitary group of U(A) generated by its commutators. It is known that CU(A) ⊂ U0(A). Denote by [Formula: see text] the affine function on T(A) defined by [Formula: see text]. We show that u can be approximated by unitaries in A with finite spectrum if and only if u ∈ CU(A) and [Formula: see text] for all n ≥ 1. Examples are given for which there are unitaries in CU(A) which cannot be approximated by unitaries with finite spectrum. Significantly these results are obtained in the absence of amenability.