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N Misra, T F Wines, C L Knopp, R Hermann, L Bond, B Mitchell, M A McGuire, J K Tinker
Staphylococcus aureus causes a chronic, contagious disease of the udder, or mastitis, in dairy cows. This infection is often refractory to antibiotic treatment, and has a significant economic impact on milk production worldwide. An effective vaccine to prevent S. aureus mastitis would improve animal health, reduce antibiotic dependence and inform human vaccine approaches. The iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) are conserved S. aureus extracellular-matrix adhesins and target vaccine antigens...
May 5, 2018: Vaccine
Diana I Saavedra, Benjamin D Rencher, Doo-Hyun Kwon, Stacey J Smith, Daniel H Ess, Merritt B Andrus
Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin (DPT) in seven steps using an intramolecular styryl Diels-Alder reaction (ISDA) strategy uniquely suited to assemble the deoxypodophyllotoxin core. Computational studies are also reported for this reaction that demonstrate the ability to overcome the limitations of slow reactivity and electronic mismatch of the diene and dieneophile...
January 17, 2018: Journal of Organic Chemistry
H Ghasemzadeh-Moghaddam, Wjb van Wamel, A van Belkum, R A Hamat, M Tavakol, V K Neela
The humoral immune responses against 46 different staphylococcal antigens in 27 bacteremia patients infected by clonally related methicillin-resistant Staphylococcus aureus (MRSA) strains of a single sequence type (ST) 239 were investigated. A group of non-infected patients (n = 31) hospitalized for different reasons served as controls. All strains were confirmed as ST 239 by S. aureus and mecA-specific PCR, spa, and multi-locus sequence typing (MLST). In each bacteremia patient, a unique pattern of S. aureus antigen-specific immune responses after infection was observed...
February 2018: European Journal of Clinical Microbiology & Infectious Diseases
Neha Misra, Tyler F Wines, Colton L Knopp, Mark A McGuire, Juliette K Tinker
Staphylococcus aureus iron-regulated surface protein A (IsdA) is a fibrinogen and fibronectin adhesin that also contributes to iron sequestration and resistance to innate immunity. IsdA is conserved in human isolates and has been investigated as a human vaccine candidate. Here we report the expression of isdA, the efficacy of anti-IsdA responses and the existence of IsdA sequence variants from bovine Staphylococcus. Clinical staphylococci were obtained from US dairy farms and assayed by PCR for the presence and expression of isdA...
May 1, 2017: FEMS Microbiology Letters
Elham Yousef Kalafi, Wooi Boon Tan, Christopher Town, Sarinder Kaur Dhillon
BACKGROUND: Monogeneans are flatworms (Platyhelminthes) that are primarily found on gills and skin of fishes. Monogenean parasites have attachment appendages at their haptoral regions that help them to move about the body surface and feed on skin and gill debris. Haptoral attachment organs consist of sclerotized hard parts such as hooks, anchors and marginal hooks. Monogenean species are differentiated based on their haptoral bars, anchors, marginal hooks, reproductive parts' (male and female copulatory organs) morphological characters and soft anatomical parts...
December 22, 2016: BMC Bioinformatics
Charlene Babra Waryah, Jully Gogoi-Tiwari, Kelsi Wells, Karina Yui Eto, Elnaz Masoumi, Paul Costantino, Michael Kotiw, Trilochan Mukkur
An extensive array of virulence factors associated with S. aureus has contributed significantly to its success as a major nosocomial pathogen in hospitals and community causing variety of infections in affected patients. Virulence factors include immune evading capsular polysaccharides, poly-N-acetyl glucosamine, and teichoic acid in addition to damaging toxins including hemolytic toxins, enterotoxins, cytotoxins, exfoliative toxin, and microbial surface components recognizing adhesive matrix molecules (MSCRAMM)...
2016: BioMed Research International
Fadi M Tayim, Laura A Flashman, Matthew J Wright, Robert M Roth, Thomas W McAllister
INTRODUCTION: Episodic memory complaints are commonly reported after traumatic brain injury (TBI). The contributions of specific memory subprocesses (encoding, consolidation, and retrieval), however, are not well understood in mild TBI (mTBI). In the present study, we evaluated subprocesses of episodic memory in patients with mTBI using the item-specific deficit approach (ISDA), which analyzes responses on list learning tasks at an item level. We also conducted exploratory analyses to evaluate the effects of complicated mTBI (comp-mTBI) on memory...
November 2016: Journal of Clinical and Experimental Neuropsychology
Weipeng Liu, Minjun Zhu, Hongxing Liu, Jitao Wei, Xiaoming Zhou, Da Xing
Searching for a strategy to enhance the efficiency of nucleic acid amplification and achieve exquisite discrimination of nucleic acids at the single-base level for biological detection has become an exciting research direction in recent years. Here, we have developed a simple and universal primer design strategy which produces a fascinating effect on isothermal strand displacement amplification (iSDA). We refer to the resultant primer as "invading stacking primer (IS-Primer)" which is based on contiguous stacking hybridization and toehold-mediated exchange reaction and function by merely changing the hybridization location of the primer...
July 15, 2016: Biosensors & Bioelectronics
P M den Reijer, E M Haisma, N A Lemmens-den Toom, J Willemse, R I Koning, R A Koning, J A A Demmers, D H W Dekkers, E Rijkers, A El Ghalbzouri, P H Nibbering, W van Wamel
BACKGROUND & AIM: The ability of Staphylococcus aureus to successfully colonize (a)biotic surfaces may be explained by biofilm formation and the actions of virulence factors. The aim of the present study was to establish the presence of 52 proteins, including virulence factors such as alpha-toxin, during biofilm formation of five different (methicillin resistant) S. aureus strains on Leiden human epidermal models (LEMs) and polystyrene surfaces (PS) using a competitive Luminex-based assay...
2016: PloS One
Bhushan J Toley, Isabela Covelli, Yevgeniy Belousov, Sujatha Ramachandran, Enos Kline, Noah Scarr, Nic Vermeulen, Walt Mahoney, Barry R Lutz, Paul Yager
We present a method of rapid isothermal amplification of DNA without initial heat denaturation of the template, and methods and probes for (a) real-time fluorescence detection and (b) lateral flow detection of amplicons. Isothermal strand displacement amplification (iSDA) can achieve >10(9)-fold amplification of the target sequence in <20 minutes at 49 °C, which makes it one of the fastest existing isothermal DNA amplification methods. iSDA initiates at sites where DNA base pairs spontaneously open or transiently convert into Hoogsteen pairs, i...
November 21, 2015: Analyst
Kohei Nishitani, Christopher A Beck, Alexander F Rosenberg, Stephen L Kates, Edward M Schwarz, John L Daiss
BACKGROUND: Because immunity against Staphylococcus aureus has not been fully elucidated, there is no diagnostic test to gauge how robust a patient's host response is likely to be. Therefore, we aimed to develop a test for specific antibodies in serum with diagnostic and prognostic potential. QUESTIONS/PURPOSES: We describe the development and validation of a multiplex immunoassay for characterizing a patient's immune response against 14 known S aureus antigens, which we then used to answer four questions: (1) Do certain antigens predominate in the immune response against S aureus? (2) Is there a predominant pattern of antigens recognized by patients and mice with infections? (3) Is the immunoglobulin G (IgG) response to any single antigen a useful predictor of ongoing S aureus infection? (4) Does measurement of the combined response against all 14 antigens provide a better predictor of ongoing infection? METHODS: A case-control study was performed...
September 2015: Clinical Orthopaedics and related Research
Mariana Rosenthal, Randi Pedersen, Scott Leibsle, Vincent Hill, Kris Carter, Dawn M Roellig
On August 27, 2014, the Idaho Department of Health and Welfare's Division of Public Health (DPH) was notified of two cases of cryptosporidiosis in siblings aged <3 years. Idaho's Southwest District Health (SWDH) investigated and found that both children had consumed raw (unpasteurized) goat milk produced at a dairy licensed by the Idaho State Department of Agriculture (ISDA) and purchased at a retail store. Milk produced before August 18, the date of illness onset, was unavailable for testing from retail stores, the household, or the dairy...
February 27, 2015: MMWR. Morbidity and Mortality Weekly Report
Jasper Swierstra, Stephanie Debets, Corné de Vogel, Nicole Lemmens-den Toom, Nelianne Verkaik, Nadjia Ramdani-Bouguessa, Marcel F Jonkman, Jan Maarten van Dijl, Ahmed Fahal, Alex van Belkum, Willem van Wamel
IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses against Staphylococcus aureus might generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 different S. aureus virulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries...
February 2015: Infection and Immunity
Sabine Rauch, Portia Gough, Hwan Keun Kim, Olaf Schneewind, Dominique Missiakas
The risk for Staphylococcus aureus bloodstream infection (BSI) is increased in immunocompromised individuals, including patients with hematologic malignancy and/or chemotherapy. Due to the emergence of antibiotic-resistant strains, designated methicillin-resistant S. aureus (MRSA), staphylococcal BSI in cancer patients is associated with high mortality; however, neither a protective vaccine nor pathogen-specific immunotherapy is currently available. Here, we modeled staphylococcal BSI in leukopenic CD-1 mice that had been treated with cyclophosphamide, a drug for leukemia and lymphoma patients...
November 2014: Infection and Immunity
Waleed Mazi, Zikra Begum, Diaa Abdulla, Ahmed Hesham, Sami Maghari, Abdullah Assiri, Abiola Senok
BACKGROUND: This study aimed to assess the impact implementation of the basic Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) practice recommendations in reducing central line-associated bloodstream infection (CLABSI) in intensive care units (ICUs). METHODS: The prospective study was conducted from January 2011-December 2012 at the 23-bed trauma ICU in Saudi Arabia. The basic SHEA/IDSA practice recommendations were introduced and implemented during the year 2012...
August 2014: American Journal of Infection Control
Catherine F M Bowden, Meghan M Verstraete, Lindsay D Eltis, Michael E P Murphy
The Isd (iron-regulated surface determinant) system is a multiprotein transporter that allows bacterium Staphylococcus aureus to take up iron from hemoglobin (Hb) during human infection. In this system, IsdB is a cell wall-anchored surface protein that contains two near iron transporter (NEAT) domains, one of which binds heme. IsdB rapidly extracts heme from Hb and transfers it to IsdA for relay into the bacterial cell. Using a series of recombinant IsdB constructs that included at least one NEAT domain, we demonstrated that both domains are required to bind Hb with high affinity (KD = 0...
April 15, 2014: Biochemistry
Yoshitaka Moriwaki, Tohru Terada, Jose M M Caaveiro, Yousuke Takaoka, Itaru Hamachi, Kouhei Tsumoto, Kentaro Shimizu
Near transporter (NEAT) domains of the iron-regulated surface determinant (Isd) proteins are essential for the import of nutritional heme from host animals to Gram-positive pathogens such as Staphylococcus aureus. The order of transfer of heme between NEAT domains occurs from IsdH to IsdA to IsdC, without any energy input despite the similarity of their three-dimensional structures. We measured the free energy of binding of heme and various metalloporphyrins to each NEAT domain and found that the affinity of heme and non-iron porphyrins for NEAT domains increased gradually in the same order as that for heme transfer...
December 10, 2013: Biochemistry
J Oltra-Cucarella, R Pérez-Elvira, P Duque
INTRODUCTION: the aim of this study is to test the encoding deficit hypothesis in Alzheimer disease (AD) using a recent method for correcting memory tests. To this end, a Spanish-language adaptation of the Free and Cued Selective Reminding Test was interpreted using the Item Specific Deficit Approach (ISDA), which provides three indices: Encoding Deficit Index, Consolidation Deficit Index, and Retrieval Deficit Index. METHODS: We compared the performances of 15 patients with AD and 20 healthy control subjects and analysed results using either the task instructions or the ISDA approach...
June 2014: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Stacey L Kolar, J Antonio Ibarra, Frances E Rivera, Joe M Mootz, Jessica E Davenport, Stanley M Stevens, Alexander R Horswill, Lindsey N Shaw
Staphylococcus aureus is a highly virulent and successful pathogen that causes a diverse array of diseases. Recently, an increase of severe infections in healthy subjects has been observed, caused by community-associated methicillin-resistant S. aureus (CA-MRSA). The reason for enhanced CA-MRSA virulence is unclear; however, work suggests that it results from hypersecretion of agr-regulated toxins, including secreted proteases. In this study, we explore the contribution of exo-proteases to CA-MRSA pathogenesis using a mutant lacking all 10 enzymes...
February 2013: MicrobiologyOpen
Marta Zapotoczna, Simon Heilbronner, Pietro Speziale, Timothy J Foster
Staphylococcus lugdunensis is the only coagulase-negative Staphylococcus species with a locus encoding iron-regulated surface determinant (Isd) proteins. In Staphylococcus aureus, the Isd proteins capture heme from hemoglobin and transfer it across the wall to a membrane-bound transporter, which delivers it into the cytoplasm, where heme oxygenases release iron. The Isd proteins of S. lugdunensis are expressed under iron-restricted conditions. We propose that S. lugdunensis IsdB and IsdC proteins perform the same functions as those of S...
December 2012: Journal of Bacteriology
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