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https://www.readbyqxmd.com/read/27821068/cp40-from-corynebacterium-pseudotuberculosis-is-an-endo-%C3%AE-n-acetylglucosaminidase
#1
Azadeh Shadnezhad, Andreas Naegeli, Mattias Collin
BACKGROUND: C. pseudotuberculosis is an important animal pathogen that causes substantial economical loss in sheep and goat farming. Zoonotic infections in humans are rare, but when they occur they are often severe and difficult to treat. One of the most studied proteins from this bacterium, the secreted protein CP40 is being developed as a promising vaccine candidate and has been characterized as a serine protease. In this study we have investigated if CP40 is an endoglycosidase rather than a protease...
November 8, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27682453/an-icosahedral-quasicrystal-and-its-1-0-crystalline-approximant-in-the-ca-au-al-system
#2
Joyce Pham, Andreas Kreyssig, Alan I Goldman, Gordon J Miller
A new icosahedral quasicrystalline phase, CaAu4.5-xAl1.5+x [0.11 ≤ x ≤ 0.40(6); CaAu4.4Al1.6, aQC = 5.383(4) Å, and Pm3̅ 5̅], and its lowest-order 1/0 cubic crystalline approximant phase, CaAu3+xAl1-x [0 ≤ x ≤ 0.31(1); a = 9.0766(5)-9.1261(8) Å, Pa3̅ (No. 205), and Pearson symbol cP40], have been discovered in the Ca-poor region of the Ca-Au-Al system. In the crystalline approximant, eight [Au3-xAl1+x] tetrahedra fill the unit cell, and each tetrahedron is surrounded by four Ca atoms, thus forming a three-dimensional network of {Ca4/4[Au3-xAl1+x]} tetrahedral stars...
October 17, 2016: Inorganic Chemistry
https://www.readbyqxmd.com/read/27677785/complement-c3-inhibitor-cp40-attenuates-xenoreactions-in-pig%C3%A2-hearts-perfused-with-human-blood
#3
Jan-Michael Abicht, Ioannis Kourtzelis, Bruno Reichart, Sophia Koutsogiannaki, Alexandra Primikyri, John D Lambris, Triantafyllos Chavakis, Lesca Holdt, Alexander Kind, Sonja Guethoff, Tanja Mayr
BACKGROUND: The complement system plays a crucial role in acute xenogeneic reactions after cardiac transplantation. We used an ex vivo perfusion model to investigate the effect of Cp40, a compstatin analog and potent inhibitor of complement at the level of C3. METHODS: Fifteen wild-type pig hearts were explanted, cardiopleged, and reperfused ex vivo after 150 minutes of cold ischemia. Hearts were challenged in a biventricular working heart mode to evaluate cardiac perfusion and function...
September 27, 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27546448/compstatin-cp40-blocks-hematin-mediated-deposition-of-c3b-fragments-on-erythrocytes-implications-for-treatment-of-malarial-anemia
#4
Margaret A Lindorfer, Erika M Cook, Edimara S Reis, Daniel Ricklin, Antonio M Risitano, John D Lambris, Ronald P Taylor
During malarial anemia, 20 uninfected red blood cells (RBCs) are destroyed for every RBC infected by Plasmodium falciparum (Pf). Increasing evidence indicates an important role for complement in destruction of uninfected RBCs. Products of RBC lysis induced by Pf, including the digestive vacuole and hematin, activate complement and promote C3 fragment deposition on uninfected RBCs. C3-opsonized cells are then subject to extravascular destruction mediated by fixed tissue macrophages which express receptors for C3 fragments...
October 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27021500/complement-inhibition-in-pre-clinical-models-of-periodontitis-and-prospects-for-clinical-application
#5
REVIEW
George Hajishengallis, Evlambia Hajishengallis, Tetsuhiro Kajikawa, Baomei Wang, Despina Yancopoulou, Daniel Ricklin, John D Lambris
Periodontitis is a dysbiotic inflammatory disease leading to the destruction of the tooth-supporting tissues. Current therapies are not always effective and this prevalent oral disease continues to be a significant health and economic burden. Early clinical studies have associated periodontitis with elevated complement activity. Consistently, subsequent genetic and pharmacological studies in rodents have implicated the central complement component C3 and downstream signaling pathways in periodontal host-microbe interactions that promote dysbiosis and inflammatory bone loss...
June 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/26977050/combined-inhibition-of-complement-and-cd14-attenuates-bacteria-induced-inflammation-in-human-whole-blood-more-efficiently-than-antagonizing-the-toll-like-receptor-4-md2-complex
#6
Alice Gustavsen, Stig Nymo, Anne Landsem, Dorte Christiansen, Liv Ryan, Harald Husebye, Corinna Lau, Søren E Pischke, John D Lambris, Terje Espevik, Tom E Mollnes
BACKGROUND: Single inhibition of the Toll-like receptor 4 (TLR4)-MD2 complex failed in treatment of sepsis. CD14 is a coreceptor for several TLRs, including TLR4 and TLR2. The aim of this study was to investigate the effect of single TLR4-MD2 inhibition by using eritoran, compared with the effect of CD14 inhibition alone and combined with the C3 complement inhibitor compstatin (Cp40), on the bacteria-induced inflammatory response in human whole blood. METHODS: Cytokines were measured by multiplex technology, and leukocyte activation markers CD11b and CD35 were measured by flow cytometry...
July 1, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/26796140/recombinant-cp40-from-corynebacterium-pseudotuberculosis-confers-protection-in-mice-after-challenge-with-a-virulent-strain
#7
Daniela Droppa-Almeida, Wanessa L P Vivas, Katharina Kelly O Silva, Andrea F S Rezende, Simone Simionatto, Roberto Meyer, Isabel B Lima-Verde, Odir Delagostin, Sibele Borsuk, Francine F Padilha
BACKGROUND: Caseous Lymphadenitis (CLA) is a contagious, infectious, chronic disease caused by Corynebacterium pseudotuberculosis, which affects mainly sheep and goats. The clinical prevalence of CLA in Brazil is 30%, resulting in decreased milk production, weight loss, and unusable meat and leather. Prophylaxis is based on vaccination; however, current vaccinations do not offer effective protection against the infection, which makes the development of a new vaccine essential to control this disease...
February 17, 2016: Vaccine
https://www.readbyqxmd.com/read/26728318/inhibition-of-pre-existing-natural-periodontitis-in-non-human-primates-by-a-locally-administered-peptide-inhibitor-of-complement-c3
#8
Tomoki Maekawa, Ruel A Briones, Ranillo R G Resuello, Joel V Tuplano, Evlambia Hajishengallis, Tetsuhiro Kajikawa, Sophia Koutsogiannaki, Cristina A G Garcia, Daniel Ricklin, John D Lambris, George Hajishengallis
AIM: Human periodontitis is associated with overactivation of complement, which is triggered by different mechanisms converging on C3, the central hub of the system. We assessed whether the C3 inhibitor Cp40 inhibits naturally occurring periodontitis in non-human primates (NHPs). MATERIALS AND METHODS: Non-human primates with chronic periodontitis were intra-gingivally injected with Cp40 either once (5 animals) or three times (10 animals) weekly for 6 weeks followed by a 6-week follow-up period...
March 2016: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/26548839/using-an-in-vitro-xenoantibody-mediated-complement-dependent-cytotoxicity-model-to-evaluate-the-complement-inhibitory-activity-of-the-peptidic-c3-inhibitor-cp40
#9
Junxiang Wang, Lu Wang, Ying Xiang, Daniel Ricklin, John D Lambris, Gang Chen
Simple and reliable methods for evaluating the inhibitory effects of drug candidates on complement activation are essential for preclinical development. Here, using an immortalized porcine aortic endothelial cell line (iPEC) as target, we evaluated the feasibility and effectiveness of an in vitro xenoantibody-mediated complement-dependent cytotoxicity (CDC) model for evaluating the complement inhibitory activity of Cp40, a potent analog of the peptidic C3 inhibitor compstatin. The binding of human xenoantibodies to iPECs led to serum dilution-dependent cell death...
January 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/25982307/compstatin-analog-cp40-inhibits-complement-dysregulation-in-vitro-in-c3-glomerulopathy
#10
Yuzhou Zhang, Dingwu Shao, Daniel Ricklin, Brieanna M Hilkin, Carla M Nester, John D Lambris, Richard J H Smith
C3 glomerulopathy (C3G) defines a group of untreatable ultra-rare renal diseases caused by uncontrolled activation of the alternative complement pathway. Nearly half of patients progress to end stage renal failure within 10 years. Cp40, a second-generation compstatin analog in clinical development, is a 14 amino-acid cyclic peptide that selectively inhibits complement activation in humans and non-human primates by binding to C3 and C3b. We hypothesized that by targeting C3 Cp40 would provide an effective treatment for C3G...
August 2015: Immunobiology
https://www.readbyqxmd.com/read/25807289/complement-inhibition-prevents-oncolytic-vaccinia-virus-neutralization-in-immune-humans-and-cynomolgus-macaques
#11
Laura Evgin, Sergio A Acuna, Christiano Tanese de Souza, Monique Marguerie, Chantal G Lemay, Carolina S Ilkow, C Scott Findlay, Theresa Falls, Kelley A Parato, David Hanwell, Alyssa Goldstein, Roberto Lopez, Sandra Lafrance, Caroline J Breitbach, David Kirn, Harold Atkins, Rebecca C Auer, Joshua M Thurman, Gregory L Stahl, John D Lambris, John C Bell, J Andrea McCart
Oncolytic viruses (OVs) have shown promising clinical activity when administered by direct intratumoral injection. However, natural barriers in the blood, including antibodies and complement, are likely to limit the ability to repeatedly administer OVs by the intravenous route. We demonstrate here that for a prototype of the clinical vaccinia virus based product Pexa-Vec, the neutralizing activity of antibodies elicited by smallpox vaccination, as well as the anamnestic response in hyperimmune virus treated cancer patients, is strictly dependent on the activation of complement...
June 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/25527190/corynebacterium-pseudotuberculosis-cp09-mutant-and-cp40-recombinant-protein-partially-protect-mice-against-caseous-lymphadenitis
#12
Judson W Silva, Daniela Droppa-Almeida, Sibele Borsuk, Vasco Azevedo, Ricardo W Portela, Anderson Miyoshi, Flávia S Rocha, Fernanda A Dorella, Wanessa L Vivas, Francine F Padilha, Maria L Hernández-Macedo, Isabel B Lima-Verde
BACKGROUND: Caseous lymphadenitis (CLA) is an infectious disease that affects small ruminants and is caused by Corynebacterium pseudotuberculosis. This disease is responsible for high economic losses due to condemnation and trim of infected carcasses, decreased leather and wool yield, loss of sales of breeding stock and deaths from internal involvement. Treatment is costly and ineffective; the most cost-effective strategy is timely immunisation. Various vaccine strategies have been tested, and recombinant vaccines are a promising alternative...
2014: BMC Veterinary Research
https://www.readbyqxmd.com/read/25468722/therapeutic-c3-inhibitor-cp40-abrogates-complement-activation-induced-by-modern-hemodialysis-filters
#13
Edimara S Reis, Robert A DeAngelis, Hui Chen, Ranillo R G Resuello, Daniel Ricklin, John D Lambris
Approximately 350,000 individuals in the United States rely on maintenance hemodialysis treatment because of end-stage renal disease. Despite improvements in dialysis technology, the mortality rate for patients treated with maintenance dialysis is still exceptionally high, with a 5-year survival rate of only 35%. Many patients succumb to conditions resulting at least in part from the chronic induction of inflammation. Among the triggers of inflammation, the complement system is of particular importance, being a well-appreciated mediator of inflammatory processes that is involved in many pathologic states...
April 2015: Immunobiology
https://www.readbyqxmd.com/read/25350518/complement-inhibition-in-a-xenogeneic-model-of-interactions-between-human-whole-blood-and-porcine-endothelium
#14
I Kourtzelis, A Ferreira, I Mitroulis, D Ricklin, S R Bornstein, C Waskow, J D Lambris, T Chavakis
Xenotransplantation (xeno-Tx) is considered as an alternative solution to overcome the shortage of human donor organs. However, the success of xeno-Tx is hindered by immune reactions against xenogeneic cells (e. g. of porcine origin). More specifically, activation of innate immune mechanisms such as complement and triggering of the coagulation cascade occur shortly after xeno-Tx, and adhesion of human leukocytes to porcine endothelium is another early critical step mediating the immune attack. To investigate the therapeutic potential of complement inhibition in the context of xenogeneic interactions, we have employed a whole-blood model in the present study...
January 2015: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/24808362/genetic-and-intervention-studies-implicating-complement-c3-as-a-major-target-for-the-treatment-of-periodontitis
#15
Tomoki Maekawa, Toshiharu Abe, Evlambia Hajishengallis, Kavita B Hosur, Robert A DeAngelis, Daniel Ricklin, John D Lambris, George Hajishengallis
Chronic periodontitis is induced by a dysbiotic microbiota and leads to inflammatory destruction of tooth-supporting connective tissue and bone. The third component of complement, C3, is a point of convergence of distinct complement activation mechanisms, but its involvement in periodontitis was not previously addressed. We investigated this question using two animal species models, namely, C3-deficient or wild-type mice and nonhuman primates (NHPs) locally treated with a potent C3 inhibitor (the compstatin analog Cp40) or an inactive peptide control...
June 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24497537/peptide-inhibitors-of-c3-activation-as-a-novel-strategy-of-complement-inhibition-for-the-treatment-of-paroxysmal-nocturnal-hemoglobinuria
#16
Antonio M Risitano, Daniel Ricklin, Yijun Huang, Edimara S Reis, Hui Chen, Patrizia Ricci, Zhuoer Lin, Caterina Pascariello, Maddalena Raia, Michela Sica, Luigi Del Vecchio, Fabrizio Pane, Florea Lupu, Rosario Notaro, Ranillo R G Resuello, Robert A DeAngelis, John D Lambris
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis due to the lack of CD55 and CD59 on affected erythrocytes. The anti-C5 antibody eculizumab has proven clinically effective, but uncontrolled C3 activation due to CD55 absence may result in opsonization of erythrocytes, possibly leading to clinically meaningful extravascular hemolysis. We investigated the effect of the peptidic C3 inhibitor, compstatin Cp40, and its long-acting form (polyethylene glycol [PEG]-Cp40) on hemolysis and opsonization of PNH erythrocytes in an established in vitro system...
March 27, 2014: Blood
https://www.readbyqxmd.com/read/23721750/effect-of-varying-the-concentrations-of-carbohydrate-and-milk-protein-in-rehydration-solutions-ingested-after-exercise-in-the-heat
#17
RANDOMIZED CONTROLLED TRIAL
Lewis J James, Gethin H Evans, Joshua Madin, Darren Scott, Michael Stepney, Russell Harris, Robert Stone, David J Clayton
The present study investigated the relationship between the milk protein content of a rehydration solution and fluid balance after exercise-induced dehydration. On three occasions, eight healthy males were dehydrated to an identical degree of body mass loss (BML, approximately 1·8%) by intermittent cycling in the heat, rehydrating with 150% of their BML over 1 h with either a 60 g/l carbohydrate solution (C), a 40 g/l carbohydrate, 20 g/l milk protein solution (CP20) or a 20 g/l carbohydrate, 40 g/l milk protein solution (CP40)...
October 2013: British Journal of Nutrition
https://www.readbyqxmd.com/read/22803713/cryptosporidium-parvum-antigens-induce-mouse-and-human-dendritic-cells-to-generate-th1-enhancing-cytokines
#18
B Bedi, J R Mead
Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhoea, which can be life-threatening in an immunocompromised host. To increase our understanding of the mechanisms that play a role in host immune responses, we investigated the effects of C. parvum antigens on the phenotype of mouse and human dendritic cells (DCs). Cryptosporidium parvum antigens induced DC activation as indicated by upregulation of the maturation marker CD209, as well as by the production of the cytokines interleukin-12 p70, IL-2, IL-1beta, IL-6...
October 2012: Parasite Immunology
https://www.readbyqxmd.com/read/21421779/targeted-allele-replacement-mutagenesis-of-corynebacterium-pseudotuberculosis
#19
Caray A Walker, Willie Donachie, David G E Smith, Michael C Fontaine
A two-step allele replacement mutagenesis procedure, using a conditionally replicating plasmid, was developed to allow the creation of targeted, marker-free mutations in Corynebacterium pseudotuberculosis. The relationship between homologous sequence length and recombination frequency was determined, and enhanced plasmid excision was observed due to the rolling-circle replication of the mutagenesis vector. Furthermore, an antibiotic enrichment procedure was applied to improve the recovery of mutants. Subsequently, as proof of concept, a marker-free, cp40-deficient mutant of C...
May 2011: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/21192786/the-complete-genome-sequence-of-corynebacterium-pseudotuberculosis-frc41-isolated-from-a-12-year-old-girl-with-necrotizing-lymphadenitis-reveals-insights-into-gene-regulatory-networks-contributing-to-virulence
#20
Eva Trost, Lisa Ott, Jessica Schneider, Jasmin Schröder, Sebastian Jaenicke, Alexander Goesmann, Peter Husemann, Jens Stoye, Fernanda Alves Dorella, Flavia Souza Rocha, Siomar de Castro Soares, Vívian D'Afonseca, Anderson Miyoshi, Jeronimo Ruiz, Artur Silva, Vasco Azevedo, Andreas Burkovski, Nicole Guiso, Olivier F Join-Lambert, Samer Kayal, Andreas Tauch
BACKGROUND: Corynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated...
2010: BMC Genomics
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