bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordant Temporal Evolution of
Pfcrt
and
Pfmdr1
Genotypes and Plasmodium falciparum In Vitro Drug Susceptibility to 4-Aminoquinolines after Drug Policy Change in French Guiana
Authors: Legrand Eric , Yrinesi Joséphine , Ekala Marie-Thérèse , Péneau Julie , Volney Béatrice , Berger Franck , Bouchier Christiane , Bertani Stéphane , Musset Lise , Meynard Jean-Baptiste , Mercereau-Puijalon Odile 
Published: January 2012

ABSTRACT

Analysis of the evolution of drug target genes under changing drug policy is needed to assist monitoring of
Plasmodium falciparum
drug resistance in the field. Here we genotype
Pfcrt
and
Pfdmr1
of 700 isolates collected in French Guiana from 2000 (5 years after withdrawal of chloroquine) to 2008, i.e., the period when the artemether-lumefantrine combination was progressively introduced and mefloquine was abandoned. Gene sequencing showed fixation of the 7G8-type
Pfcrt
SMVNT resistance haplotype and near fixation of the NYCDY
Pfdmr1
haplotype.
Pfdmr1
gene copy number correlated with 50% inhibitory concentrations of mefloquine and halofantrine (
r
= 0.64 and 0.47, respectively,
n
= 547); its temporal changes paralleled changes in
in vitro
mefloquine susceptibility. However, the molecular parameters studied did not account for the regained
in vitro
susceptibility to chloroquine and showed a poor correlation with susceptibility to artemether, lumefantrine, or quinine. Identification of novel markers of resistance to these antimalarials is needed in this South American area.
Hydrolysis Spectrum Extension of CMY-2-Like β-Lactamases Resulting from Structural Alteration in the Y-X-N Loop
Authors: Dahyot Sandrine , Mammeri Hedi 
Published: January 2012

ABSTRACT

The
Citrobacter freundii
isolate CHA, which was responsible for postoperative peritonitis after 10 days of cefepime therapy, displayed a phenotype of resistance consistent with extended-spectrum AmpC (ESAC) β-lactamase. The chromosome-borne
bla
AmpC-CHA
gene was amplified and sequenced, revealing five amino acid substitutions, I125V, R148H, Q196H, V305A, and V348A, in the product compared to the sequence of native AmpC. A cloning experiment yielded the
Escherichia coli
TOP10(pAmpC-CHA) strain, which was resistant to all extended-spectrum cephalosporins (ESCs), including cefepime. To ascertain whether the R148H substitution accounted for the hydrolysis spectrum extension, it was reverted by site-directed mutagenesis. The resulting
E. coli
TOP10(pAmpC-CHA-H148R) strain was fully susceptible to cefepime, thus confirming that the Arg-148 replacement was mandatory for substrate profile enlargement. To further characterize the phenotypical and biochemical effects induced by the R148H change, it was introduced by site-directed mutagenesis into the CMY-2 β-lactamase, which is structurally related to the chromosome-borne cephalosporinase of
C. freundii
. The CMY-2-R148H variant conferred increased MICs of ESCs, whereas those of carbapenems were unchanged even in a porin-deficient
E. coli
strain. Moreover, it exhibited increased catalytic efficiency (
k
cat
/

K
m

) toward ceftazidime (100-fold) due to an enhanced hydrolysis rate (
k
cat
), whereas the enzymatic parameters toward imipenem were unchanged. The structural analysis of the AmpC variant showed that the R148H replacement occurred in the loop containing the Y-X-N motif, which is the counterpart of the SDN loop in class A β-lactamases. This study shows that the Y-X-N loop is a novel hot spot for mutations accounting for hydrolysis spectrum extension in CMY-2-type enzymes.
Antimicrobial Activity of the Investigational Pleuromutilin Compound BC-3781 Tested against Gram-Positive Organisms Commonly Associated with Acute Bacterial Skin and Skin Structure Infections
Authors: Sader Helio S. , Biedenbach Douglas J. , Paukner Susanne , Ivezic-Schoenfeld Zrinka , Jones Ronald N. 
Published: January 2012

ABSTRACT

BC-3781 is a novel semisynthetic pleuromutilin antimicrobial agent developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested by the broth microdilution method against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI. BC-3781 exhibited potent activity against methicillin-resistant
Staphylococcus aureus
(MIC
50/90
, 0.12/0.25 μg/ml), coagulase-negative staphylococci (MIC
50/90
, 0.06/0.12 μg/ml), β-hemolytic streptococci (MIC
50/90
, 0.03/0.06 μg/ml), viridans group streptococci (MIC
50/90
, 0.12/0.5 μg/ml), and
Enterococcus faecium
(including vancomycin-nonsusceptible strains) (MIC
50/90
, 0.12/2 μg/ml). Compared with other antibiotics in use for the treatment of ABSSSI, BC-3781 displayed the lowest MICs and only a minimal potential for cross-resistance with other antimicrobial classes.
A Novel Membrane Protein, VanJ, Conferring Resistance to Teicoplanin
Authors: Novotna Gabriela , Hill Chris , Vincent Karen , Liu Chang , Hong Hee-Jeon 
Published: January 2012

ABSTRACT

Bacterial resistance to the glycopeptide antibiotic teicoplanin shows some important differences from the closely related compound vancomycin. They are currently poorly understood but may reflect significant differences in the mode of action of each antibiotic.
Streptomyces coelicolor
possesses a
vanRSJKHAX
gene cluster that when expressed confers resistance to both vancomycin and teicoplanin. The resistance to vancomycin is mediated by the enzymes encoded by
vanKHAX
, but not by
vanJ. vanHAX
effect a reprogramming of peptidoglycan biosynthesis, which is considered to be generic, conferring resistance to all glycopeptide antibiotics. Here, we show that
vanKHAX
are not in fact required for teicoplanin resistance in
S. coelicolor
, which instead is mediated solely by
vanJ. vanJ
is shown to encode a membrane protein oriented with its C-terminal active site exposed to the extracytoplasmic space. VanJ also confers resistance to the teicoplanin-like antibiotics ristocetin and A47934 and to a broad range of semisynthetic teicoplanin derivatives, but not generally to antibiotics or semisynthetic derivatives with vancomycin-like structures.
vanJ
homologues are found ubiquitously in streptomycetes and include
staP
from the
Streptomyces toyocaensis
A47934 biosynthetic gene cluster. While overexpression of
staP
also conferred resistance to teicoplanin, similar expression of other
vanJ
homologues (SCO2255, SCO7017, and SAV5946) did not. The
vanJ
and
staP
orthologues, therefore, appear to represent a subset of a larger protein family whose members have acquired specialist roles in antibiotic resistance. Future characterization of the divergent enzymatic activity within this new family will contribute to defining the molecular mechanisms important for teicoplanin activity and resistance.
Mechanisms of Action of Escapin, a Bactericidal Agent in the Ink Secretion of the Sea Hare Aplysia californica: Rapid and Long-Lasting DNA Condensation and Involvement of the OxyR-Regulated Oxidative Stress Pathway
Authors: Ko Ko-Chun , Tai Phang C. , Derby Charles D. 
Published: January 2012

ABSTRACT

The marine snail
Aplysia californica
produces escapin, an
l
-amino acid oxidase, in its defensive ink. Escapin uses
l
-lysine to produce diverse products called escapin intermediate products of
l
-lysine (EIP-K), including α-amino-ε-caproic acid, Δ
1
-piperidine-2-carboxylic acid, and Δ
2
-piperidine-2-carboxylic acid. EIP-K and H
2
O
2
together, but neither alone, is a powerful bactericide. Here, we report bactericidal mechanisms of escapin products on
Escherichia coli
. We show that EIP-K and H
2
O
2
together cause rapid and long-lasting DNA condensation: 2-min treatment causes significant DNA condensation and killing, and 10-min treatment causes maximal effect, lasting at least 70 h. We isolated two mutants resistant to EIP-K plus H
2
O
2
, both having a single missense mutation in the oxidation regulatory gene,
oxyR
. A complementation assay showed that the mutated gene,
oxyR
(
A233V
), renders resistance to EIP-K plus H
2
O
2
, and a gene dosage effect leads to reduction of resistance for strains carrying wild-type
oxyR
. Temperature stress with EIP-K does not produce the bactericidal effect, suggesting the effect is due to a specific response to oxidative stress. The null mutant for any single DNA-binding protein—Dps, H-NS, Hup, Him, or MukB—was not resistant to EIP-K plus H
2
O
2
, suggesting that no single DNA-binding protein is necessary to mediate this bactericidal effect, but allowing for the possibility that EIP-K plus H
2
O
2
could function through a combination of DNA-binding proteins. The bactericidal effect of EIP-K plus H
2
O
2
was eliminated by the ferrous ion chelator 1,10-phenanthroline, and it was reduced by the hydroxyl radical scavenger thiourea, suggesting hydroxyl radicals mediate the effects of EIP-K plus H
2
O
2
.
Energy acquisition and allocation patterns of lake whitefish (Coregonus clupeaformis) are modified when dreissenids are present
Authors: Rennie Michael D. , Johnson Timothy B. , Sprules W. Gary 
Published: January 2012

We evaluated the effects of dreissenid-induced food web changes on rates of lake whitefish ( Coregonus clupeaformis ) energy acquisition and allocation in North American populations. We used mass-balance models of lake whitefish growth and methylmercury accumulation in 17 populations with and without dreissenids present to estimate and contrast rates of activity (ACT), consumption (C) and conversion efficiency (V). Historical estimates were also generated for a single lake whitefish population during dreissenid establishment. Bioenergetic estimates from both scenarios were compared with densities of Diporeia , a historically important diet component of lake whitefish. Mean lake whitefish ACT and C estimates in populations with dreissenids were significantly greater: 1.3–2 times those of populations without dreissenids. Conversion efficiencies scaled positively and significantly, while C and ACT varied negatively and significantly with Diporeia abundance. Our results suggest that changes in lake whitefish activity may affect density estimates — and ultimately sustainable management quotas — for this species. Our results also show that reported declines in lake whitefish individual growth rates in South Bay, Lake Huron, can be explained by increased activity rates due to increased foraging activity in an energetically depleted prey community.
Different organochlorine contaminant profiles in groups of flounders (Platichthys flesus) from sampling locations around Denmark
Authors: Vorkamp Katrin , Svendsen Tore Christian , Rønsholdt Bent , Larsen Martin Mørk 
Published: January 2012

Flounders ( Platichthys flesus ) from the waters around Denmark were analysed for their organochlorine (OC) profile to study whether fish from the same genetic population could be separated into characteristic subpopulations, based on their feeding grounds. The chemical analysis of fish liver provided a data set of 16 OC compounds in 94 samples from 2004 to 2006. Except for hexachlorocyclohexane, OC compounds were intercorrelated, indicating similar environmental fate and bioaccumulation. OC profiles are less affected than absolute concentrations by potentially confounding biological factors and thus more suitable for studies of intrapopulation differences in relation to feeding grounds. Principal component analysis grouped the samples according to locations. All but three of the 94 samples could be reclassified. Samples from the same and additional locations collected in 2003 provided validation, with only few misclassifications. This statistical separation likely reflects location-specific pollutant patterns in sediments and biota, even on the relatively small scale of this study. Thus, despite the lack of genetic differences, characteristic subpopulations of flounders could be identified with separate feeding grounds. OC profiles have been used increasingly to distinguish stocks.
Mycobacterium marinuminfections in humans and tracing of its possible environmental sources
Authors: Slany Michal , Jezek Petr , Fiserova Vera , Bodnarova Monika , Stork Jiri , Havelkova Marta , Kalat Frantisek , Pavlik Ivo 
Published: January 2012

The low frequency of nontuberculous mycobacterial infections, nonspecific symptoms for individual mycobacteria, and the lack of specific identification methods could alter correct diagnosis. This study presents a combined microbiology and molecular-based approach for Mycobacterium marinum detection in four aquarists with cutaneous mycobacterial infection. Simultaneously, ecology screening for M. marinum presence in the aquarists’ fish tanks was performed. A total of 38 mycobacterial isolates originated from four human patients (n = 20), aquarium animals (n = 8), and an aquarium environment (n = 10). Isolate identification was carried out using 16S rRNA sequence analysis. A microbiology-based approach, followed by 16S rRNA sequence analysis, was successfully used for detection of M. marinum in all four patients. Animal and environmental samples were simultaneously examined, and a total of seven mycobacterial species were isolated: Mycobacterium chelonae , Mycobacterium fortuitum , Mycobacterium gordonae , Mycobacterium kansasii , Mycobacterium mantenii , Mycobacterium marinum , and Mycobacterium peregrinum . The presence of M. marinum was proven in the aquarium environments of two patients. Although M. marinum is described as being present in water, it was detected only in fish.
Diversity and antimicrobial activities of the fungal endophyte community associated with the traditional Brazilian medicinal plant Solanum cernuum Vell. (Solanaceae)
Authors: Vieira Mariana L.A. , Hughes Alice F.S. , Gil Viviane B. , Vaz Aline B.M. , Alves Tânia M.A. , Zani Carlos L. , Rosa Carlos A. , Rosa Luiz H. 
Published: January 2012

The diversity and antimicrobial activity of endophytic fungi associated with the Brazilian medicinal plant Solanum cernuum Vell. were studied during summer and winter seasons. A total of 246 fungal isolates were obtained, including 225 filamentous fungi and 21 yeasts. They were identified by morphological, physiological, and molecular methods. Fifty-five different taxa represented by the phyla Ascomycota (33 taxa), Basidiomycota (21 taxa), and Zygomycota (one taxon) were identified. The most abundant taxa were closely related to Arthrobotrys foliicola , Colletotrichum gloeosporioides , Coprinellus radians , Glomerella acutata , Diatrypella frostii , Phoma glomerata , Mucor sp., Phlebia subserialis , Phoma moricola , Phanerochaete sordida , and Colletotrichum sp. A total of 265 fungal extracts were screened and 64 (26.01%) displayed antimicrobial activities. Among these extracts, 18 (28.12%) presented antibacterial and antifungal activities, 42 (65.62%) displayed selective antibacterial activity, and four (6.25%) exhibited only antifungal activity. The best values of minimum inhibitory concentration were obtained from extracts of Cryptococcus rajasthanensis , Glomerella acutata, Leptosphaeria sp., and Phoma glomerata ranging from 7.8 to 15.62 µg/mL. This study is the first survey of the endophytic fungi community associated with S. cernuum, and our results show that they can represent a promising source of bioactive compounds.
Role forcheRofVibrio fischeriin theVibrio–squid symbiosis
Authors: DeLoney-Marino Cindy R. , Visick Karen L. 
Published: January 2012

Upon hatching, the Hawaiian squid Euprymna scolopes is rapidly colonized by its symbiotic partner, the bioluminescent marine bacterium Vibrio fischeri . Vibrio fischeri cells present in the seawater enter the light organ of juvenile squid in a process that requires bacterial motility. In this study, we investigated the role chemotaxis may play in establishing this symbiotic colonization. Previously, we reported that V. fischeri migrates toward numerous attractants, including N-acetylneuraminic acid (NANA), a component of squid mucus. However, whether or not migration toward an attractant such as squid-derived NANA helps the bacterium to localize toward the light organ is unknown. When tested for the ability to colonize juvenile squid, a V. fischeri chemotaxis mutant defective for the methyltransferase CheR was outcompeted by the wild-type strain in co-inoculation experiments, even when the mutant was present in fourfold excess. Our results suggest that the ability to perform chemotaxis is an advantage during colonization, but not essential.
Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF
Authors: Arul Albert Baskar , Savarimuthu Ignacimuthu , Alsaif Mohammed A. , Numair Khalid S. Al 
Published: January 2012

This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting DMH (20 mg·(kg body mass)–1) once weekly for 15 consecutive weeks, and administering a multivitamin supplement in 3 regimes (initiation, post-initiation, and entire experimental period) for 32 weeks. We studied lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) in the circulation and in the tissues, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and non-enzymatic antioxidant-reduced glutathione) of the tissues, aberrant crypt foci (ACF), and histopathological alterations. DMH-induced rats had an increase in lipid peroxidation products and a lower antioxidant status compared with control animals. Multivitamin and mineral supplementation during the initiation, post-initiation, and the entire study period significantly decreased the levels of lipid peroxidation products in circulation and colonic tissues, significantly elevated the activities of the antioxidant enzymes and reduced glutathione to near normalcy in DMH-induced rats. The incidence of ACF was reduced to 84.1% in rats supplemented with multivitamin and minerals for the entire study and prevented the colonic tissue from histopathological alterations induced by DMH.
Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart disease resulting in “HUFA deficiency”
Authors: Rupp Heinz , Rupp Thomas P. , Alter Peter , Maisch Bernhard 
Published: January 2012

The causes of reduced levels of omega-3 and omega-6 highly unsaturated fatty acids (“HUFA deficiency”) in heart failure remain unresolved. HUFA profiles were examined in the serum of 331 patients with failing versus nonfailing heart disease. Arachidonic acid was positively correlated (P < 0.001) with eicosapentaenoic acid (EPA) (r = 0.40) and docosahexaenoic acid (DHA) (r = 0.53) and negatively with palmitic (r = 0.42), palmitoleic (r = 0.38), and oleic acid (r = 0.48). Delta-5 desaturase activity was reduced (P < 0.01) in heart failure patients with low ejection fraction, dilatation, increased wall stress, and reduced heart rate variability (SDNN). In these patients, the reduced (P < 0.01) HUFA and increased palmitic (P < 0.01) and oleic acid (P = 0.05) arose from separate influences involving reduced cardiac contractility (arachidonic acid and palmitic acid predicted by ejection fraction) and chamber dilatation (DHA and oleic acid predicted by end-diastolic diameter). A low DHA (0.2%–0.9% versus 1.4%–3.1%) was associated (P < 0.025) with atrial dilatation (44 ± 8 mm versus 40 ± 8 mm). Equidirectional but less pronounced effects on HUFA were induced by sympathetic activation and (or) insulin resistance (fat and sugar fed to deoxycorticosterone acetate (DOCA)-salt rats) but not by compensated cardiac overload alone (DOCA-salt or aortic constriction), or reduced fatty acid oxidation (CPT-1 inhibition). Based on administration of omega-3 HUFA (OMACOR), dilatation is identified as a target for 1–2 g omega-3 HUFA·day–1. Interventions for reduced arachidonic acid remain to be explored.
Impact of Circulating Vitamin D Binding Protein Levels on the Association between 25-Hydroxyvitamin D and Pancreatic Cancer Risk: A Nested Case–Control Study
Authors: Weinstein Stephanie J. , Stolzenberg-Solomon Rachael Z. , Kopp William , Rager Helen , Virtamo Jarmo , Albanes Demetrius 
Published: January 2012

Abstract
High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case–control study of 234 cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. ORs and 95% CIs were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r = 0.27, P &lt; 0.0001), and DBP was inversely associated with pancreatic cancer risk (OR = 0.66, 95% CI = 0.39–1.12, for the highest vs. lowest quartile; Ptrend = 0.02). Importantly, this association seemed to have a threshold between quartiles 2 to 4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR = 0.33, 95% CI = 0.16–0.70 for highest vs. lowest quartile; Ptrend = 0.002), with no association in men with lower serum 25(OH)D (OR = 1.28, 95% CI = 0.62–2.61 for highest vs. lowest quartile, Ptrend 0.63, Pinteraction = 0.01). Men with higher 25(OH)D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR = 5.01, 95% CI 2.33–10.78, for highest vs. lowest quartile; Ptrend &lt; 0.0001), while risk was weakly inversely associated with serum 25(OH)D when DBP concentrations were higher (Pinteraction = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH)D and reduce free 25(OH)D bioavailability. Simultaneous examination of DBP and 25(OH)D may be important in determining the association of vitamin D with cancer risk. Cancer Res; 72(5); 1190–8. ©2012 AACR.