bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of OprD in Carbapenem-Intermediate and -Susceptible Strains of Pseudomonas aeruginosa Isolated from Patients with Bacteremia in a Spanish Multicenter Study
Authors: Ocampo-Sosa Alain A. , Cabot Gabriel , Rodríguez Cristina , Roman Elena , Tubau Fe , Macia María D. , Moya Bartolomé , Zamorano Laura , Suárez Cristina , Peña Carmen , Domínguez María A. , Moncalián Gabriel , Oliver Antonio , Martínez-Martínez Luis ,   the Spanish Network for Research in Infectious Diseases (REIPI)
Published: January 2012

ABSTRACT

We investigated the presence of OprD mutations in 60 strains of metallo-ß-lactamase-negative
Pseudomonas aeruginosa
intermediately susceptible (IS [
n
= 12]; MIC = 8 μg/ml) or susceptible (S [
n
= 48]; MICs ≤ 1 to 4 μg/ml) to imipenem and/or meropenem that were isolated from patients with bacteremia in order to evaluate their impact on carbapenem susceptibility profiles. The presence of mutations in
oprD
was detected by sequencing analysis. OprD expression was assessed by both outer membrane protein (OMP) analysis and real-time PCR (RT-PCR). Fourteen (23%) isolates had an OprD identical to that of PAO1, and OprD modifications were detected in 46 isolates (77%). Isolates were classified as OprD “full-length types” (T1 [
n
= 40, including both wild-type OprD and variants showing several polymorphisms]) and OprD “deficient types” (T2 [
n
= 3 for OprD frameshift mutations] and T3 [
n
= 17 for premature stop codons in
oprD
]). RT-PCR showed that 5 OprD type T1 isolates presented reduced transcription of
oprD
(0.1- to 0.4-fold compared to PAO1), while
oprD
levels increased more than 2-fold over that seen with PAO1 in 4 OprD type T1 isolates. A total of 50% of the isolates belonging to OprD “deficient types” were susceptible to both carbapenems, and 40% were susceptible to meropenem and intermediately susceptible to imipenem. Only one isolate (5%) within this group was intermediately susceptible to both carbapenems, and one (5%) was susceptible to imipenem and intermediately susceptible to meropenem. We concluded that OprD inactivating mutations in clinical isolates of
P. aeruginosa
are not restricted only to carbapenem-resistant isolates but are also found in isolates with imipenem or meropenem MICs of only 0.06 to 4 μg/ml.
Complete Sequence of a Novel 178-Kilobase Plasmid Carrying
bla
NDM-1
in a Providencia stuartii Strain Isolated in Afghanistan
Authors: Mc Gann Patrick , Hang Jun , Clifford Robert J. , Yang Yu , Kwak Yoon I. , Kuschner Robert A. , Lesho Emil P. , Waterman Paige E. 
Published: January 2012

ABSTRACT

In response to global concerns over the spread of the New Delhi metallo-β-lactamase gene 1,
bla
NDM-1
, a monthly surveillance program was initiated in September 2010. All carbapenem-resistant Gram-negative strains forwarded to our facility are screened for this gene. To date, 321 carbapenem-resistant isolates, encompassing 11 bacterial species, have been tested. In February 2011, two strains of
Providencia stuartii
, submitted from a military hospital in Afghanistan, tested positive for
bla
NDM-1
. Both strains were identical by pulsed-field gel electrophoresis (PFGE).
bla
NDM-1
was carried on a large plasmid, pMR0211, which was sequenced by emulsion PCR and pyrosequencing. pMR0211 is 178,277 bp in size and belongs to incompatibility group A/C. The plasmid consists of a backbone with considerable homology to pAR060302 from
Escherichia coli
, and it retains many of the antibiotic resistance genes associated with it. The plasmid also shares common elements with the pNDM-HK plasmid, including
bla
NDM-1
,
armA
, and
sul1
. However, gene orientation is reversed, and a 3-kb fragment from this region is absent from pMR0211. pMR0211 also contains additional genes, including the aminoglycoside-modifying enzyme loci
aadA
and
aac
(
6
′), the quinolone resistance gene
qnrA
, a gene with highest homology to a U32 family peptidase from
Shewanella amazonensis
, and the
bla
OXA-10
gene. The finding of this gene in an intrinsically colistin-resistant species such as
Providencia stuartii
is especially worrisome, as it renders the organism resistant to nearly every available antibiotic. The presence of multiple insertion sequences and transposons flanking the region containing the
bla
NDM-1
gene further highlights the potential mobility associated with this gene.
Pharmacokinetics of Different Dosing Strategies of Oral Posaconazole in Patients with Compromised Gastrointestinal Function and Who Are at High Risk for Invasive Fungal Infection
Authors: Cornely Oliver A. , Helfgott David , Langston Amelia , Heinz Werner , Vehreschild Jörg-Janne , Vehreschild Maria J. G. T. , Krishna Gopal , Ma Lei , Huyck Susan , McCarthy Michael C. 
Published: January 2012

ABSTRACT
The aim of this study was to assess different dosing strategies that may result in increased posaconazole bioavailability in patients with compromised gastrointestinal function and at high risk for invasive fungal infections. Patients undergoing chemotherapy and at risk for compromised gastrointestinal function received open-label posaconazole at 200 mg three times daily (TID) on days 1 to 8. Patients were randomized to one of three open-label dosing regimens of posaconazole on days 9 to 15: 200 mg TID, 400 mg twice daily (BID), or 400 mg TID. The plasma concentrations of interest on days 8 and 15 were 500 and 700 ng/ml, respectively; day 2 plasma concentrations of 250 and 350 ng/ml were chosen as levels that might result in steady-state concentrations of >500 and >700 ng/ml, respectively. A total of 75 patients enrolled; 52/75 (69%) completed the study, and 49/75 were included in the pharmacokinetic analyses. Mean plasma concentrations were 230, 346, and 637 ng/ml on days 2, 3, and 8, respectively. The day 15 values were 660, 930, and 671 ng/ml for 200 mg TID, 400 mg BID, and 400 mg TID, respectively. In 12 patients with a day 8 posaconazole concentration of <250 ng/ml, an overall benefit of the higher two doses was not apparent, suggesting that a subset of patients has low steady-state plasma concentrations. A change in dosing regimen on day 9 did not lead to higher exposures in these “poor absorbers” on day 15. Poor absorption may be enhanced with a high-fat meal, a nutritional supplement, or acidification.
An Antibiotic That Inhibits a Late Step in Wall Teichoic Acid Biosynthesis Induces the Cell Wall Stress Stimulon in Staphylococcus aureus
Authors: Campbell Jennifer , Singh Atul K. , Swoboda Jonathan G. , Gilmore Michael S. , Wilkinson Brian J. , Walker Suzanne 
Published: January 2012

ABSTRACT

Wall teichoic acids (WTAs) are phosphate-rich, sugar-based polymers attached to the cell walls of most Gram-positive bacteria. In
Staphylococcus aureus
, these anionic polymers regulate cell division, protect cells from osmotic stress, mediate host colonization, and mask enzymatically susceptible peptidoglycan bonds. Although WTAs are not required for survival
in vitro
, blocking the pathway at a late stage of synthesis is lethal. We recently discovered a novel antibiotic, targocil, that inhibits a late acting step in the WTA pathway. Its target is TarG, the transmembrane component of the ABC transporter (TarGH) that exports WTAs to the cell surface. We examined here the effects of targocil on
S. aureus
using transmission electron microscopy and gene expression profiling. We report that targocil treatment leads to multicellular clusters containing swollen cells displaying evidence of osmotic stress, strongly induces the cell wall stress stimulon, and reduces the expression of key virulence genes, including
dltABCD
and capsule genes. We conclude that WTA inhibitors that act at a late stage of the biosynthetic pathway may be useful as antibiotics, and we present evidence that they could be particularly useful in combination with beta-lactams.
MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis
Authors: Vesić Dušanka , Kristich Christopher J. 
Published: January 2012

ABSTRACT

Enterococcus faecalis
is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify
E. faecalis
strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in
murAA. murAA
is predicted to encode a UDP-
N
-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-
N
-acetylglucosamine to UDP-
N
-acetylglucosamine-enolpyruvate. In-frame deletion of
murAA
, but not its homolog in the
E. faecalis
genome (
murAB
), led to increased susceptibility of
E. faecalis
to cephalosporins. Furthermore, expression of
murAA
enhanced cephalosporin resistance in an
E. faecalis
mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in
E. faecalis
physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of
E. faecalis
to cephalosporins.
Small Plasmids Harboring
qnrB19
: a Model for Plasmid Evolution Mediated by Site-Specific Recombination at
oriT
and Xer Sites
Authors: Tran Tung , Andres Patricia , Petroni Alejandro , Soler-Bistué Alfonso , Albornoz Ezequiel , Zorreguieta Angeles , Reyes-Lamothe Rodrigo , Sherratt David J. , Corso Alejandra , Tolmasky Marcelo E. 
Published: January 2012

ABSTRACT

Plasmids pPAB19-1, pPAB19-2, pPAB19-3, and pPAB19-4, isolated from
Salmonella
and
Escherichia coli
clinical strains from hospitals in Argentina, were completely sequenced. These plasmids include the
qnrB19
gene and are 2,699, 3,082, 2,989, and 2,702 nucleotides long, respectively, and they share extensive homology among themselves and with other previously described small
qnrB19
-harboring plasmids. The genetic environment of
qnrB19
in all four plasmids is identical to that in these other plasmids and in transposons such as Tn
2012
, Tn
5387
, and Tn
5387
-like. Nucleotide sequence comparisons among these and previously described plasmids showed a variable region characterized by being flanked by an
oriT
locus and a Xer recombination site. We propose that this arrangement could play a role in the evolution of plasmids and present a model for DNA swapping between plasmid molecules mediated by site-specific recombination events at
oriT
and a Xer target site.
Dynamic Interaction between Fluconazole and Amphotericin B against Cryptococcus gattii
Authors: Santos Julliana Ribeiro Alves , Gouveia Ludmila Ferreira , Taylor Erika Linzi Silva , Resende-Stoianoff Maria Aparecida , Pianetti Gerson Antônio , César Isabela Costa , Santos Daniel Assis 
Published: January 2012

ABSTRACT

Cryptococcus gattii
is the main pathogen of cryptococcosis in healthy patients and is treated mainly with fluconazole and amphotericin B. The combination of these drugs has been questioned because the mechanisms of action could lead to a theoretical antagonistic interaction. We evaluated distinct parameters involved in the
in vitro
combination of fluconazole and amphotericin B against
Cryptococcus gattii
. Fourteen strains of
C. gattii
were used for the determination of MIC, fractional inhibitory concentration, time-kill curve, and postantifungal effect (PAFE). Ergosterol quantification was performed to evaluate the influence of ergosterol content on the interaction between these antifungals. Interaction between the drugs varied from synergistic to antagonistic depending on the strain and concentration tested. Increasing fluconazole levels were correlated with an antagonistic interaction. A total of 48 h was necessary for reducing the fungal viability in the presence of fluconazole, while 12 h were required for amphotericin B. When these antifungals were tested in combination, fluconazole impaired the amphotericin B activity. The ergosterol content decreased with the increase of fluconazole levels and it was correlated with the lower activity of amphotericin B. The PAFE found varied from 1 to 4 h for fluconazole and from 1 to 3 h for amphotericin B. The interaction of fluconazole and amphotericin B was concentration-dependent and special attention should be directed when these drugs are used in combination against
C. gattii
.
Evolutionary Changes in Antimicrobial Resistance of Invasive Neisseria meningitidis Isolates in Belgium from 2000 to 2010: Increasing Prevalence of Penicillin Nonsusceptibility
Authors: Bertrand Sophie , Carion Françoise , Wintjens René , Mathys Vanessa , Vanhoof Raymond 
Published: January 2012

ABSTRACT

This study was conducted to evaluate the evolution of the antimicrobial susceptibility of
Neisseria meningitidis
causing invasive diseases in Belgium in the period of January 2000 to December 2010. A total of 1,933 cases of
N. meningitidis
from invasive infections were analyzed by antimicrobial susceptibility testing at the Belgian Meningococcal Reference Centre. The majority of strains were susceptible to antibiotics that are currently used for the treatment and prophylaxis of meningococcal disease, but the prevalence of clinical isolates with reduced susceptibility to penicillin increased over the years. The phenotyping, genotyping, and determination of MICs of penicillin G were performed. The systematic shift of the curves toward higher penicillin MICs in the susceptible population indicated that this population became less sensitive to penicillin in this period. A 402-bp DNA fragment in the 3′ end of
penA
was sequenced for the 296 nonsusceptible meningococcal strains isolated between 2000 and 2010 to examine the genetic diversity and evolution of their
penA
gene. In conclusion, the data obtained in our study support the statement that the position of penicillin G as a first choice in the treatment of invasive meningococcal diseases in Belgium should be reexamined. Despite an important number of isolates displaying a reduced susceptibility to penicillin, at present the expanded-spectrum cephalosporins, such as ceftriaxone, are not affected. The follow-up of the evolutionary changes in antimicrobial resistance has also proved to be essential for the recommendation of an appropriate antimicrobial treatment for invasive meningococcal diseases.
Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice
Authors: Washino Takuya , Moroda Masataka , Iwakura Yoichiro , Aosai Fumie 
Published: January 2012

ABSTRACTInterleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection withToxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed inT. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c+cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c+cells also produced IL-10, IL-1β, and IL-6, CD4+T cells fromT. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of theT. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.
Both Phthiocerol Dimycocerosates and Phenolic Glycolipids Are Required for Virulence of Mycobacterium marinum
Authors: Yu Jia , Tran Vanessa , Li Ming , Huang Xinghua , Niu Chen , Wang Decheng , Zhu Jianghua , Wang Jianping , Gao Qian , Liu Jun 
Published: January 2012

ABSTRACT

Phthiocerol dimycocerosates (PDIMs) and structurally related phenolic glycolipids (PGLs) are complex cell wall lipids unique to pathogenic mycobacteria. While these lipids have been extensively studied in recent years, there are conflicting reports on some aspects of their biosynthesis and on the role of PDIMs and especially PGLs in virulence of
Mycobacterium tuberculosis
. This has been complicated by the natural deficiency of PGLs in many clinical strains of
M. tuberculosis
and the frequent loss of PDIMs in laboratory
M. tuberculosis
strains. In this study, we isolated seven mutants of
Mycobacterium marinum
deficient in PDIMs and/or PGLs in which multiple genes of the PDIM/PGL biosynthetic locus were disrupted by transposon insertion. Zebrafish infection experiments showed that
M. marinum
strains lacking one or both of these lipids were avirulent, suggesting that both PDIMs and PGLs are required for virulence. We also found that these strains were hypersensitive to antibiotics and exhibited increased cell wall permeability. Our studies provide new insights into the biosynthesis of PDIMs/PGLs and may help us to understand the role of PDIMs and PGLs in
M. tuberculosis
virulence.
Willingness to use HIV pre-exposure prophylaxis and the likelihood of decreased condom use are both associated with unprotected anal intercourse and the perceived likelihood of becoming HIV positive among Australian gay and bisexual men
Authors: Holt Martin , Murphy Dean A , Callander Denton , Ellard Jeanne , Rosengarten Marsha , Kippax Susan C , de Wit John B F 
Published: January 2012

ObjectivesTo investigate willingness to use HIV pre-exposure prophylaxis (PrEP) and the likelihood of decreased condom use among Australian gay and bisexual men.MethodsA national, online cross-sectional survey was conducted in April to May 2011. Bivariate relationships were assessed with χ2or Fisher's exact test. Multivariate logistic regression analysis was performed to assess independent relationships with primary outcome variables.ResultsResponses from 1161 HIV-negative and untested men were analysed. Prior use of antiretroviral drugs as PrEP was rare (n=6). Just over a quarter of the sample (n=327; 28.2%) was classified as willing to use PrEP. Willingness to use PrEP was independently associated with younger age, having anal intercourse with casual partners (protected or unprotected), having fewer concerns about PrEP and perceiving oneself to be at risk of HIV. Among men who were willing to use PrEP (n=327), only 26 men (8.0%) indicated that they would be less likely to use condoms if using PrEP. The likelihood of decreased condom use was independently associated with older age, unprotected anal intercourse with casual partners (UAIC) and perceiving oneself to be at increased risk of HIV.ConclusionsThe Australian gay and bisexual men the authors surveyed were cautiously optimistic about PrEP. The minority of men who expressed willingness to use PrEP appear to be appropriate candidates, given that they are likely to report UAIC and to perceive themselves to be at risk of HIV.
Clinical Outcomes of Traditional Chinese Medicine Compound Formula in Treating Sleep-Disordered Breathing Patients
Authors: Wu Yi-Hong , Wei Yi-Chia , Tai Yu-Shan , Chen Kuan-Jen , Li Hsueh-Yu 
Published: January 2012

Sleep-Disordered Breathing (SDB) is a prevalent affliction, which can range from simple snoring to severely obstructive sleep apnea. Compared to current treatment options of SDB, traditional Chinese medicine (TCM) provides a noninvasive way to relieve SDB-related symptoms and deaths. The purpose of this retrospective study was to observe the progression of adult SDB patients who had taken compound formula SZ + NUH (concentrated herbal granules) for four weeks. Depending on subjects’ individual needs, minor additions of formulas or single herbs were allowed. We found a significant amount of relief from snoring among the 118 enrolled subjects, according to before-after scores observed through the Snore Outcome Survey (SOS). Furthermore, as projected from the moderate linear correlation in before-after scores, we inferred that those cases with more severe snoring at baseline had greater improvement after treatment. Excessive daytime sleepiness was also significantly improved according to the results of the Epworth Sleepiness Scale (ESS). Assessment, using the SF-36 (Taiwanese version) revealed possible benefits of SZ + NUH in improving multiple facets of subjects’ quality of life. During treatment, no significant side effects occurred. In conclusion, the TCM compound formula based on SZ + NUH could be a safe and effective option for SDB treatment.
On the Expressive Power of Multiple Heads in CHR
Authors: Di Giusto Cinzia , Gabbrielli Maurizio , Meo Maria Chiara 
Published: January 2012

Constraint Handling Rules (CHR) is a committed-choice declarative language that has been originally designed for writing constraint solvers and is nowadays a general purpose language. CHR programs consist of multiheaded guarded rules which allow to rewrite constraints into simpler ones until a solved form is reached. Many empirical evidences suggest that multiple heads augment the expressive power of the language, however no formal result in this direction has been proved, so far.
In the first part of this article we analyze the Turing completeness of CHR with respect to the underlying constraint theory. We prove that if the constraint theory is powerful enough then restricting to single head rules does not affect the Turing completeness of the language. On the other hand, differently from the case of the multiheaded language, the single head CHR language is not Turing powerful when the underlying signature (for the constraint theory) does not contain function symbols.
In the second part we prove that, no matter which constraint theory is considered, under some reasonable assumptions it is not possible to encode the CHR language (with multi-headed rules) into a single headed language while preserving the semantics of the programs. We also show that, under some stronger assumptions, considering an increasing number of atoms in the head of a rule augments the expressive power of the language.
These results provide a formal proof for the claim that multiple heads augment the expressive power of the CHR language.