bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inactivation of AHLs by Ochrobactrum sp. A44 depends on the activity of a novel class of AHL acylase
Authors: Czajkowski Robert , Krzyżanowska Dorota , Karczewska Joanna , Atkinson Steve , Przysowa Joanna , Lojkowska Ewa , Williams Paul , Jafra Sylwia 
Published: June 2010

SummaryThe soil isolate Ochrobactrum sp. A44 inactivates N‐acyl homoserine lactone (AHL) quorum sensing signal molecules and is capable of quenching the AHL‐dependent virulence of Pectobacterium carotovorum in planta. To characterize this AHL inactivating activity, Ochrobactrum cell extracts were prepared and their capacity to degrade a broad range of AHLs was determined. AHLs with acyl chains ranging from C4 to C14 with or without 3‐oxo or 3‐hydroxy substituents were all inactivated to varying extents; long chain AHLs were generally more susceptible than short chain compounds irrespective of the three position substituent. HPLC and LC‐tandem mass spectrometry of the AHL degradation products revealed that the AHL inactivating activity present in the Ochrobactrum cell extract cleaved the AHL amide bond. To identify the gene(s) responsible for AHL degradation, Ochrobactrum sp. A44 was subjected to random transposon (Tn) mutagenesis and the resulting mutants screened for the loss of AHL acylase activity. The Tn insertion in mutant A6731 was mapped to a gene termed aiiO, the translated product of which belongs to the α/β hydrolase superfamily which constitutes a novel type of AHL acylase.
Molecular identification of reproductive cells released from Cypassis irregularis Nigrini (Radiolaria)
Authors: Kimoto Katsunori , Yuasa Tomoko , Takahashi Osamu 
Published: June 2010

SummaryThe mechanisms of the extensive distribution of radiolarian‐affiliated sequences from clone libraries of marine picoeukaryotes from deeper water remain poorly understood. Here, we describe an event that could explain this phenomenon. A polycystine radiolarian species, Cypassis irregularis Nigrini, released a large number of pico‐size cells under culture conditions. The diameters of the cells averaged ∼3 µm and the 18S rDNA sequences fell within those of typical radiolarian families. This finding suggests that the radiolarian sequences found in the picoeukaryote size fraction from deep water are from swarmers or gametes released for reproduction. Thus, the deep ocean is expected to aid in the widespread dispersal of the genetic material of eukaryotes.
Cloning and Occurrence of
czrC
, a Gene Conferring Cadmium and Zinc Resistance in Methicillin-Resistant
Staphylococcus aureus
CC398 Isolates
Authors: Cavaco L. M. , Hasman H. , Stegger M. , Andersen P. S. , Skov R. , Fluit A. C. , Ito T. , Aarestrup F. M. 
Published: June 2010

ABSTRACT

We recently reported a phenotypic association between reduced susceptibility to zinc and methicillin resistance in
Staphylococcus aureus
CC398 isolates from Danish swine (F. M. Aarestrup, L. M. Cavaco, and H. Hasman, Vet. Microbiol.
142:
455-457, 2009). The aim of this study was to identify the genetic determinant causing zinc resistance in CC398 and examine its prevalence in isolates of animal and human origin. Based on the sequence of the staphylococcal cassette chromosome
mec
(SCC
mec
) element from methicillin-resistant
S. aureus
(MRSA) CC398 strain SO385, a putative metal resistance gene was identified in strain 171 and cloned in
S. aureus
RN4220. Furthermore, 81 MRSA and 48 methicillin-susceptible
S. aureus
(MSSA) strains, isolated from pigs (31 and 28) and from humans (50 and 20) in Denmark, were tested for susceptibility to zinc chloride and for the presence of a putative resistance determinant,
czrC
, by PCR. The cloning of
czrC
confirmed that the zinc chloride and cadmium acetate MICs for isogenic constructs carrying this gene were increased compared to those for
S. aureus
RN4220. No difference in susceptibility to sodium arsenate, copper sulfate, or silver nitrate was observed. Seventy-four percent (
n
= 23) of the animal isolates and 48% (
n
= 24) of the human MRSA isolates of CC398 were resistant to zinc chloride and positive for
czrC
. All 48 MSSA strains from both human and pig origins were found to be susceptible to zinc chloride and negative for
czrC
. Our findings showed that
czrC
is encoding zinc and cadmium resistance in CC398 MRSA isolates, and that it is widespread both in humans and animals. Thus, resistance to heavy metals such as zinc and cadmium may play a role in the coselection of methicillin resistance in
S. aureus
.
Association of the Extended-Spectrum β-Lactamase Gene
bla
TLA-1
with a Novel IS
CR
Element, IS
CR20
Authors: Berçot Beatrice , Poirel Laurent , Silva-Sanchez Jesus , Nordmann Patrice 
Published: June 2010

ABSTRACT

The
bla
TLA-1
gene encoding an extended-spectrum β-lactamase was identified in 11 enterobacterial isolates from Mexico City, Mexico. This gene was located on different plasmids and plasmid types with different sizes and incompatibility groups. It was associated with a novel insertion sequence, IS
CR20
, encoding a putative transposase that shared only 20% amino acid identity with the most closely related transposase of IS
CR1
. The IS
CR20
element provided specific promoter sequences for expression of the
bla
TLA-1
gene.
Small-Molecule Screening Using a Whole-Cell Viral Replication Reporter Gene Assay Identifies 2-{[2-(Benzoylamino)Benzoyl]Amino}-Benzoic Acid as a Novel Antiadenoviral Compound
Authors: Andersson Emma K. , Strand Mårten , Edlund Karin , Lindman Kristina , Enquist Per-Anders , Spjut Sara , Allard Annika , Elofsson Mikael , Mei Ya-Fang , Wadell Göran 
Published: June 2010

ABSTRACTAdenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their antiadenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential antiadenoviral compounds. The assay is unique in that it is based on a replication-competent adenovirus type 11p green fluorescent protein (GFP)-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expressionin vitroby ≥80%, but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.
Impact of Multidrug-Resistant
Pseudomonas aeruginosa
Bacteremia on Patient Outcomes
Authors: Tam Vincent H. , Rogers Cary A. , Chang Kai-Tai , Weston Jaye S. , Caeiro Juan-Pablo , Garey Kevin W. 
Published: June 2010

ABSTRACT

Trends of rising rates of resistance in
Pseudomonas aeruginosa
make selection of appropriate empirical therapy increasingly difficult, but whether multidrug-resistant (MDR)
P. aeruginosa
is associated with worse clinical outcomes is not well established. The objective of this study was to determine the impact of MDR (resistance to three or more classes of antipseudomonal agents)
P. aeruginosa
bacteremia on patient outcomes. We performed a retrospective cohort study of adult patients with
P. aeruginosa
bacteremia from 2005 to 2008. Patients were identified by the microbiology laboratory database, and pertinent clinical data were collected. Logistic regression was used to explore independent risk factors for 30-day mortality. Classification and regression tree analysis was used to determine threshold breakpoints for continuous variables. Kaplan-Meier survival analysis was used to compare time to mortality, after normalization of the patients' underlying risks by propensity scoring. A total of 109 bacteremia episodes were identified; 25 episodes (22.9%) were caused by MDR
P. aeruginosa
. Patients with MDR
P. aeruginosa
bacteremia were more likely to receive inappropriate empirical therapy (44.0% and 6.0%, respectively;
P
< 0.001) and had longer prior hospital stays (32.6 ± 37.3 and 14.4 ± 43.6 days, respectively;
P
= 0.046). Multivariate regression revealed that 30-day mortality was associated with multidrug resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9 to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an APACHE II score of ≥22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time to mortality was also shorter in the MDR cohort (
P
= 0.011). Multidrug resistance is a significant risk factor for 30-day mortality in patients with
P. aeruginosa
bacteremia; efforts to curb the spread of MDR
P. aeruginosa
could be beneficial.
Easy Strategy To Protect Antimicrobial Peptides from Fast Degradation in Serum
Authors: Knappe Daniel , Henklein Petra , Hoffmann Ralf , Hilpert Kai 
Published: June 2010

ABSTRACT

Antimicrobial peptides are promising novel peptide leads, but their low serum stability often limits their further consideration in drug development programs. Here, we describe a generally applicable strategy to stabilize peptides against serum proteases by replacing arginine residues with α-amino-3-guanidino-propionic acid (Agp). Peptide NH
2
-RRWRIVVIRVRR-CONH
2
was nearby totally degraded after 8 h in mouse serum, whereas the variant with Agp substituted was degraded less than 20%. The antimicrobial activity was not affected.
Emergence of Resistance among USA300 Methicillin-Resistant
Staphylococcus aureus
Isolates Causing Invasive Disease in the United States
Authors: McDougal Linda K. , Fosheim Gregory E. , Nicholson Ainsley , Bulens Sandra N. , Limbago Brandi M. , Shearer Julia E. S. , Summers Anne O. , Patel Jean B. 
Published: June 2010

ABSTRACT

USA300 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates are usually resistant only to oxacillin, erythromycin, and, increasingly, levofloxacin. Of these, oxacillin and levofloxacin resistances are chromosomally encoded. Plasmid-mediated clindamycin, mupirocin, and/or tetracycline resistance has been observed among USA300 isolates, but these descriptions were limited to specific patient populations or isolated occurrences. We examined the antimicrobial susceptibilities of invasive MRSA isolates from a national surveillance population in order to identify USA300 isolates with unusual, possibly emerging, plasmid-mediated antimicrobial resistance. DNA from these isolates was assayed for the presence of resistance determinants and the presence of a pSK41-like conjugative plasmid. Of 823 USA300 isolates, 72 (9%) were tetracycline resistant; 69 of these were doxycycline susceptible and
tet
K
positive, and 3 were doxycycline resistant and
tet
M
positive. Fifty-one (6.2%) isolates were clindamycin resistant and
erm
C
positive; 22 (2.7%) isolates were high-level mupirocin resistant (
mup
A
positive); 5 (0.6%) isolates were trimethoprim-sulfamethoxazole (TMP-SMZ) resistant, of which 4 were
dfr
A
positive; and 7 (0.9%) isolates were gentamicin resistant and
aac
6
′-
aph
2
″ positive. Isolates with pSK41-like plasmids (
n
= 24) were positive for
mup
A
(
n
= 19),
dfr
A
(
n
= 6),
aac
6
′-
aph
2
″ (
n
= 6),
tet
M
(
n
= 2), and
erm
C
(
n
= 8); 20 pSK41-positive isolates were positive for two or more resistance genes. Conjugative transfer of resistance was demonstrated between four gentamicin- and mupirocin-resistant and three gentamicin- and TMP-SMZ-resistant USA300 isolates; transconjugants harbored a single pSK41-like plasmid, which was PCR positive for
aac
6
′-
aph
2
″ and either
mup
A
and/or
dfr
A
. USA300 and USA100 isolates from the same state with identical resistance profiles contained pSK41-like plasmids with indistinguishable restriction and Southern blot profiles, suggesting horizontal plasmid transfer between USA100 and USA300 isolates.
In Vitro
Activity of the New Multivalent Glycopeptide-Cephalosporin Antibiotic TD-1792 against Vancomycin-Nonsusceptible
Staphylococcus
Isolates
Authors: Leuthner Kimberly D. , Vidaillac Celine , Cheung Chrissy M. , Rybak Michael J. 
Published: June 2010

ABSTRACT

TD-1792 is a glycopeptide-cephalosporin heterodimer antibiotic with activity against a broad spectrum of Gram-positive pathogens that includes methicillin-susceptible and -resistant
Staphylococcus aureus
. The objective of the present study was to evaluate the
in vitro
activity of TD-1792 against a collection of clinical isolates of vancomycin-intermediate
Staphylococcus
spp. (VISS), heteroresistant VISS (hVISS), and vancomycin-resistant
S. aureus
(VRSA). The TD-1792, vancomycin, daptomycin, linezolid, and quinupristin-dalfopristin MICs and minimum bactericidal concentrations (MBCs) were determined for 50 VISS/hVISS isolates and 3 VRSA isolates. Time-kill experiments (TKs) were then performed over 24 h with two vancomycin-intermediate
S. aureus
strains and two VRSA strains, using each agent at multiples of the MIC. TD-1792 and daptomycin were also evaluated in the presence and absence of 50% human serum to determine the effects of the proteins on their activities. Most of the VISS/hVISS isolates were susceptible to all agents except vancomycin. TD-1792 exhibited the lowest MIC values (MIC
90
= 0.125 μg/ml), followed by quinupristin-dalfopristin and daptomycin (MIC
90
= 1 μg/ml) and then linezolid (MIC
90
= 2 μg/ml). The presence of serum resulted in a 2- to 8-fold increase in the TD-1792 and daptomycin MIC values. In TKs, QD demonstrated bactericidal activity at multiples of the MIC that simulated therapeutic levels, whereas linezolid was only bacteriostatic. Both TD-1792 and daptomycin demonstrated rapid bactericidal activities against all isolates tested. The presence of proteins had only a minimal impact on the activity of TD-1792 in TKs. TD-1792 exhibited significant
in vitro
activity against multidrug-resistant
Staphylococcus
isolates and represents a promising candidate for the treatment of infections caused by Gram-positive organisms.
Assessment of Pandemic and Seasonal Influenza A (H1N1) Virus Susceptibility to Neuraminidase Inhibitors in Three Enzyme Activity Inhibition Assays
Authors: Nguyen Ha T. , Sheu Tiffany G. , Mishin Vasiliy P. , Klimov Alexander I. , Gubareva Larisa V. 
Published: June 2010

ABSTRACTThe neuraminidase inhibitors (NAIs) zanamivir and oseltamivir are currently the only antiviral drugs effective for the treatment and prophylaxis of 2009 pandemic influenza A (H1N1) virus infections. The proven potential of these viruses to acquire NAI resistance during treatment emphasizes the need to assess their NAI susceptibility. The 50% inhibitory concentrations (IC50s) are known to vary depending on the neuraminidase inhibition (NI) test used; however, few side-by-side comparisons of different NI assays have been done. In the present study, a panel of 11 isolates representing 2009 seasonal and pandemic influenza H1N1 viruses, including oseltamivir-resistant H275Y variants, were tested in three functional NI assays: chemiluminescent (CL), fluorescent (FL), and colorimetric (CM). The sensitivities of the viruses to zanamivir, oseltamivir, and three investigational NAIs (peramivir, R-125489, and A-315675) were assessed. All isolates with the exception of H275Y variants were sensitive to all five NAIs by all three NI assays. The H275Y variants showed substantially elevated IC50s against oseltamivir and peramivir. The three NI assays generally yielded consistent results; thus, the choice of NI assay does not appear to affect conclusions based on drug susceptibility surveillance. Each assay, however, offers certain advantages compared to the others: the CL assay required less virus volume and the FL assay provided the greatest difference in the IC50s between the wild type and the variants, whereas the IC50s obtained from the CM assay may be the most predictive of the drug concentrations needed to inhibit enzyme activity in humans. It would be desirable to develop an NI assay which combines the advantages of all three currently available assays but which lacks their shortcomings.
Improving Quinolone Use in Hospitals by Using a Bundle of Interventions in an Interrupted Time Series Analysis
Authors: Willemsen Ina , Cooper Ben , van Buitenen Carin , Winters Marjolein , Andriesse Gunnar , Kluytmans Jan 
Published: June 2010

ABSTRACT

The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in
Escherichia coli
isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for
E. coli
isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month,
P
< 0.001). Intervention 2, introduction of a new antibiotic guideline and education program, was associated with a stepwise reduction in the overall use of quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions.
Different Classes of Antibiotics Differentially Influence Shiga Toxin Production
Authors: McGannon Colleen Marie , Fuller Cynthia Ann , Weiss Alison Ann 
Published: June 2010

ABSTRACT

Shiga toxin (Stx) in
Escherichia coli
O157:H7 is encoded as a late gene product by temperate bacteriophage integrated into the chromosome. Phage late genes, including
stx
, are silent in the lysogenic state. However, stress signals, including some induced by antibiotics, trigger the phage to enter the lytic cycle, and phage replication and Stx production occur concurrently. In addition to the Stx produced by O157:H7, phage produced by O157:H7 can infect harmless intestinal
E. coli
and recruit them to produce Shiga toxin. To understand how antibiotics influence Stx production, Stx lysogens were treated with different classes of antibiotics in the presence or absence of phage-sensitive
E. coli
, and Stx-mediated inhibition of protein synthesis was monitored using luciferase-expressing Vero cells. Growth-inhibitory levels of antibiotics suppressed Stx production. Subinhibitory levels of antibiotics that target DNA synthesis, including ciprofloxacin (CIP) and trimethoprim-sulfamethoxazole, increased Stx production, while antibiotics that target the cell wall, transcription, or translation did not. More Stx was produced when
E. coli
O157:H7 was incubated in the presence of phage-sensitive
E. coli
than when grown as a pure culture. Remarkably, very high levels of Stx were detected even when growth of O157:H7 was completely suppressed by CIP. In contrast, azithromycin significantly reduced Stx levels even when O157:H7 viability remained high.
Porphyromonas gingivalisLipids Inhibit Osteoblastic Differentiation and Function
Authors: Wang Yu-Hsiung , Jiang Jin , Zhu Qiang , AlAnezi Amer Z. , Clark Robert B. , Jiang Xi , Rowe David W. , Nichols Frank C. 
Published: June 2010

ABSTRACTPorphyromonas gingivalisproduces unusual sphingolipids that are known to promote inflammatory reactions in gingival fibroblasts and Toll-like receptor 2 (TLR2)-dependent secretion of interleukin-6 from dendritic cells. The aim of the present study was to examine whetherP. gingivalislipids inhibit osteoblastic function. Total lipids fromP. gingivalisand two fractions, phosphoglycerol dihydroceramides and phosphoethanolamine dihydroceramides, were prepared free of lipid A. Primary calvarial osteoblast cultures derived from 5- to 7-day-old CD-1 mice were used to examine the effects ofP. gingivalislipids on mineralized nodule formation, cell viability, apoptosis, cell proliferation, and gene expression.P. gingivalislipids inhibited osteoblast differentiation and fluorescence expression of pOBCol2.3GFP in a concentration-dependent manner. However,P. gingivalislipids did not significantly alter osteoblast proliferation, viability, or apoptosis. When administered during specific intervals of osteoblast growth,P. gingivalistotal lipids demonstrated inhibitory effects on osteoblast differentiation only after the proliferation stage of culture. Reverse transcription-PCR confirmed the downregulation of osteoblast marker genes, including Runx2, ALP, OC, BSP, OPG, and DMP-1, with concurrent upregulation of RANKL, tumor necrosis factor alpha, and MMP-3 genes.P. gingivalistotal lipids and lipid fractions inhibited calvarial osteoblast gene expression and functionin vivo, as determined by the loss of expression of another osteoblast differentiation reporter, pOBCol3.6GFPcyan, and reduced uptake of Alizarin complexone stain. Finally, lipid inhibition of mineral nodule formationin vitrowas dependent on TLR2 expression. Our results indicate that inhibition of osteoblast function and gene expression byP. gingivalislipids represents a novel mechanism for altering alveolar bone homeostasis at periodontal disease sites.