A5075589181- Adenosine and Purinergic Signaling
- Bacterial Infections and Vaccines
- Reproductive tract infections research
- Antibiotic Resistance in Bacteria
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Pneumonia and Respiratory Infections
- Bacterial Genetics and Biotechnology
- Microbial Natural Products and Biosynthesis
- Streptococcal Infections and Treatments
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Nitric Oxide and Endothelin Effects
- Syphilis Diagnosis and Treatment
- Enzyme Structure and Function
- Antimicrobial Resistance in Staphylococcus
- Pharmacological Receptor Mechanisms and Effects
- Chemical Synthesis and Analysis
- Gastroesophageal reflux and treatments
- Monoclonal and Polyclonal Antibodies Research
- Calcium signaling and nucleotide metabolism
- Neuroscience of respiration and sleep
- Pharmacological Effects of Natural Compounds
- Ion channel regulation and function
- Antibiotics Pharmacokinetics and Efficacy
University of North Carolina at Chapel Hill
2015-2024
McKesson (United States)
2020
University of North Carolina Health Care
2013
University of Bonn
2009
Heinrich Heine University Düsseldorf
2009
SLAC National Accelerator Laboratory
2008
Stanford Synchrotron Radiation Lightsource
2008
Wesleyan University
2006
University of Liège
2006
Indiana University School of Medicine
1993-2006
ABSTRACT Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm characterize a second (F89) with high-level cefixime resistance France most likely caused treatment failure cefixime. F89 examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. multiantigen...
Observation that the G protein-coupled P2U receptor (P2Y2 receptor) is activated by UTP as well ATP provided first indication a class of uridine nucleotide-responsive receptors might exist. This hypothesis was confirmed our identification nucleotide-specific on C6-2B rat glioma cells and recent cloning two receptors, P2Y6 [J. Biol. Chem. 270:26152-26158 (1995)] P2Y4 270:30849-30852 (1995) J. 270:30845-30848 (1995)]. The relative nucleotide selectivities these nucleotide-activated have not...
1. The coding sequence of the P2Y1-purinoceptor was cloned from a human genomic library. 2. open reading frame encodes protein 373 amino acids that is 83% identical to previously chick and turkey > or = 95% homologous recently rat, mouse, bovine P2Y1-purinoceptors. 3. stably expressed in 1321N1 astrocytoma cells using retroviral vector. Although agonist, 2MeSATP, had no effect on inositol phosphate accumulation infected with virus. No 2MeSATP cyclic AMP observed P2Y1-receptor-expressing...
ABSTRACT The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as cefixime ceftriaxone have been reported. aim this study was determine the correlation different polymorphisms in penA , mtrR porB1b ( penB ), ponA genes N. ceftriaxone. Eighteen gonococcal (Cef i ) two susceptible were characterized using serovar determination, antibiograms, multiantigen sequence typing (NG-MAST), sequencing alleles. For Cef...
Extracellular ATP and its metabolite adenosine regulate mucociliary clearance in airway epithelia. Little has been known, however, regarding the actual concentrations thin (∼7 μm) liquid layer lining native surfaces link between release/metabolism autocrine/paracrine regulation of epithelial function. In this study, chimeric Staphylococcus aureus protein A-luciferase (SPA-luc) was bound to endogenous antigens on primary human bronchial (HBE) cell surface assessed real-time (ASL). resting...
P2Y purinergic receptors previously have been shown to couple either activation of phospholipase C through a pertussis toxin-insensitive mechanism or inhibition adenylyl cyclase toxin-sensitive members the G1 family G proteins. These and other pharmacological data strongly suggest that multiple exist. Webb et al. [FEBS Lett. 324:219-225 (1993)] cloned cDNA that, when expressed in frog oocytes, displayed general characteristics receptor but whose second messenger linkage was not resolved. We...
Extracellular ATP regulates several elements of the mucus clearance process important for pulmonary host defense. However, mechanisms mediating release onto airway surfaces remain unknown. Mitochondrial voltage-dependent anion channels (mt-VDACs) translocate a variety metabolites, including and ADP, across mitochondrial outer membrane, plasmalemmal splice variant (pl-VDAC-1) has been proposed to mediate translocation plasma membrane. We tested involvement VDAC-1 in series studies murine...
All strains of Neisseria gonorrhoeae with reduced susceptibility to ceftriaxone and cefixime (cephalosporin-intermediate-resistant [Ceph(i)] strains) contain a mosaic penA allele encoding penicillin-binding protein 2 (PBP 2) nearly 60 amino acid differences compared the sequence wild-type PBP 2, together set resistance determinants (i.e., mtrR, penB, and/or ponA1) that are required for high-level penicillin resistance. To define individual contributions these cefixime, we created isogenic...
Mutations in penicillin-binding protein 2 (PBP 2) encoded by mosaic penA alleles are crucial for intermediate resistance to the expanded-spectrum cephalosporins ceftriaxone and cefixime Neisseria gonorrhoeae. Three of ∼60 mutations present penA, G545S, I312M, V316T, have been reported be responsible increased resistance, especially [Takahata, S., et al. (2006) Antimicrob. Agents Chemother. 50, 3638−3645]. However, we observed that minimum inhibitory concentrations (MICs) penicillin,...
ABSTRACT Chromosomally mediated penicillin resistance in Neisseria gonorrhoeae occurs part through alterations penicillin-binding proteins (PBPs) and a decrease outer membrane permeability. However, the genetic molecular mechanisms of transformation penicillin-susceptible strain N. to high-level have not been clearly elucidated. Previous studies suggested that PBP 1 were involved resistance. In this study, we identified single amino acid mutation located 40 acids N terminal active-site...
ABSTRACT The importance of the mtrCDE -encoded efflux pump in conferring chromosomally mediated penicillin resistance on certain strains Neisseria gonorrhoeae was determined by using genetic derivatives penicillin-sensitive strain FA19 bearing defined mutations ( mtrR , penA and penB ) donated a clinical isolate (FA6140) expressing high-level to antimicrobial hydrophobic agents (HAs). When introduced into transformation, single base pair deletion promoter sequence from FA6140 sufficient...
The agonist selectivity for adenosine di- and triphosphates was determined the human P2Y1 receptor stably expressed in 1321N1 astrocytoma cells studied under conditions which nucleotide metabolism both minimized assessed. Cells were grown at low density on glass coverslips, encased a flow-through chamber, continuously superfused with medium, Ca2+ responses to nucleotides quantified. Superfusion high performance liquid chromatographically purified ADP, ATP, 2-methylthio-ADP, 2-methylthio-ATP...
Neisseria gonorrhoeae has two porins, PIA and PIB, whose genes (porA porB, respectively) are alleles of a single por locus. We recently demonstrated that penB mutations at positions 120 121 in which presumed to reside loop 3 forms the pore constriction zone, confer intermediate-level resistance penicillin tetracycline (M. Olesky, M. Hobbs, R. A. Nicholas, Antimicrob. Agents Chemother. 46:2811-2820, 2002). In present study, we investigated electrophysiological properties as well solute...
PenB is the third resistance determinant in stepwise acquisition of multiple genes chromosomally mediated resistant Neisseria gonorrhoeae (CMRNG). Alterations por(IB), one two alleles at por locus that encodes outer membrane protein porin IB (PIB), were recently reported to be responsible for increased penicillin and tetracycline conferred by penB, but specific mutations conferring antibiotic not identified experimentally. To determine which amino acids PIB confer resistance, we transformed...
The P2Y<sub>1</sub> receptor is a membrane-bound G protein-coupled stimulated by adenine nucleotides. Using alanine scanning mutagenesis, the role in activation of charged amino acids (Asp, Glu, Lys, and Arg) cysteines extracellular loops (EL) human P2Y<sub>1</sub>receptor has been investigated. mutant receptors were expressed COS-7 cells measured for stimulation phospholipase C induced potent agonist 2-methylthioadenosine-5′-diphosphate (2-MeSADP). In addition to single point mutations, all...
ABSTRACT Neisseria gonorrhoeae becomes resistant to tetracycline by two major mechanisms: expression of a plasmid-encoded TetM protein and mutations in endogenous genes (chromosomally mediated resistance). Early studies Sparling colleagues (P. F. A. J. Sarubbi, E. Blackman, Bacteriol. 124:740-749, 1975) demonstrated that three were involved high-level chromosomally resistance (MIC ≥ 2 μg/ml): ery-2 (now referred as mtrR ), penB , tet-2 . While the identities first are known, gene has not...
Resistance to ceftriaxone in
The UDP-3- O -( R -3-hydroxyacyl)- N -acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, outer membrane anchor lipopolysaccharide and lipooligosaccharide Gram-negative bacteria. development LpxC-targeting antibiotics toward clinical therapeutics has been hindered by limited antibiotic profile reported non-hydroxamate inhibitors unexpected cardiovascular toxicity observed certain hydroxamate non–hydroxamate-based inhibitors. Here, we report preclinical...
We conducted a mutational analysis of residues potentially involved in the adenine nucleotide binding pocket human P2Y<sub>1</sub>receptor. Mutated receptors were expressed COS-7 cells with an epitope tag that permitted confirmation expression plasma membrane, and agonist-promoted inositol phosphate accumulation was assessed as measure receptor activity. Residues transmembrane helical domains (TMs) 3, 5, 6, 7 predicted by molecular modeling to be ligand recognition replaced alanine and, some...
The nucleotide selectivities of the human P2Y(4) (hP2Y(4)) and rat (rP2Y(4)) receptor stably expressed in 1321N1 astrocytoma cells were determined by measuring increases intracellular [Ca(2+)] under conditions that minimized metabolism, bioconversion, endogenous release. In expressing hP2Y(4) receptor, UTP, GTP, ITP all increased with a rank order potency UTP (0.55) > GTP (6.59) = (7.38), (EC(50), microM). ATP, CTP, xanthine 5'-triphosphate (XTP), diadenosine 5',5"'-P(1), P(4)-tetraphosphate...