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Alpha toxin

Góra Bartłomiej, Gofron Zygmunt, Grosiak Magdalena, Aptekorz Małgorzata, Kazek Beata, Kocelak Piotr, Radosz-Komoniewska Halina, Chudek Jerzy, Martirosian Gayane
Infectious factors are taken into consideration in pathophysiology of autism spectrum disorders (ASD). ASD patients often suffer from gastrointestinal disorders. The intestinal microbiota of autistic patients significantly differs from that in healthy individuals. The aim of the study was to compare the profile of toxins produced by C. perfringens strains isolated from feces of children with ASD, with healthy individuals and obese subjects. This study included 111 strains of C. perfringens: 49 isolates from 29 children with ASD, 30 - from 17 healthy individuals and 32 - from 24 young obese subjects...
March 8, 2018: Anaerobe
Baifen Song, Hongyu Cui, Longzhu Ju, Li Song, Lijie Tang, Yijing Li
We previously developed a stable and marker-free Lactobacillus casei strain (PPαT Δupp) that contained a chromosomally integrated expression cassette (PPαT) that enabled the surface expression of the Clostridium perfringens alpha toxin. To measure immune responses against the alpha toxin, specific-pathogen-free BALB/c mice were inoculated with L. casei PPαT Δupp by oral gavage. Then, specific immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM)...
March 7, 2018: Microbial Pathogenesis
Monifa A Fahie, Lucas Liang, Alzira R Avelino, Bach Pham, Patanachai Limpikirati, Richard W Vachet, Min Chen
Cytolysin A (ClyA) is a water-soluble alpha pore-forming toxin that assembles to form an oligomeric pore on host cell membranes. The ClyA monomer possesses an α-helical bundle with a β-sheet subdomain (the β-tongue) previously believed to be critical for pore assembly and/or insertion. Oligomerization of ClyA pores transforms the β-tongue into a helix-turn-helix that embeds into the lipid bilayer. Here, we show that mutations of the β-tongue did not prevent oligomerization or transmembrane insertion. Instead, β-tongue substitution mutants yielded pores with decreased conductance while a deletion mutation resulted in pores that rapidly closed following membrane association...
February 28, 2018: Scientific Reports
Taylor S Cohen, Michelle L Boland, Brandon B Boland, Virginia Takahashi, Andrey Tovchigrechko, Young Lee, Aimee D Wilde, Mark J Mazaitis, Omari Jones-Nelson, Christine Tkaczyk, Rajiv Raja, C Kendall Stover, Bret R Sellman
Clinical severity of Staphylococcus aureus respiratory infection correlates with alpha toxin (AT) expression. AT activates the NLRP3 inflammasome; deletion of Nlrp3, or AT neutralization, protects mice from lethal S. aureus pneumonia. We tested the hypothesis that this protection is not due to a reduction in inflammasome-dependent cytokines (IL-1β/IL-18) but increased bactericidal function of macrophages. In vivo, neutralization of AT or NLRP3 improved bacterial clearance and survival, while blocking IL-1β/IL-18 did not...
February 27, 2018: Cell Reports
Alexey Ruzin, Yuling Wu, Li Yu, Xiang-Qing Yu, David E Tabor, Hoyin Mok, Christine Tkaczyk, Kathryn Jensen, Terramika Bellamy, Lorin Roskos, Mark T Esser, Hasan S Jafri
Objectives: MEDI4893 is a novel, long-acting human monoclonal antibody targeting Staphylococcus aureus (SA) alpha toxin (AT). This report presents the results of the exploratory analyses from a randomised phase 1 dose-escalation study in healthy human subjects receiving single intravenous MEDI4893 doses or placebo. Methods: Anti-AT antibodies and AT expression were measured as described previously. Nasal swabs were analysed by culture and PCR. Data were summarised by treatment groups and visits by using SAS System Version 9...
2018: Clinical & Translational Immunology
Jun-Seob Kim, Allen B Schantz, Sooyeon Song, Manish Kumar, Thomas K Wood
GhoT is a bacterial toxin of the type V toxin/antitoxin system that allows Escherichia coli to reduce its metabolism in response to oxidative and bile stress. GhoT functions by increasing membrane permeability and reducing both ATP levels and the proton motive force. However, how GhoT damages the inner membrane has not been elucidated. Here we investigated how GhoT damages membranes by studying its interaction with lipid bilayers and determined that GhoT does not cause macroscopic disruption of the lipid bilayer to increase membrane permeability to the dye carboxyfluorescein...
February 19, 2018: Biochemical and Biophysical Research Communications
Barbara Hofbauer, Jan Vomacka, Matthias Stahl, Vadim S Korotkov, Megan C Jennings, William Wuest, Stephan A Sieber
Staphylococcus aureus is a major bacterial pathogen that invades and damages host tissue by the expression of devastating toxins. We here performed a phenotypic screen of 35 molecules that were structurally inspired by previous hydroxyamide-based S. aureus virulence inhibitors compiled from commercial sources or designed and synthesized de novo. One of the most potent compounds, AV73, did not only reduce hemolytic alpha-hemolysin production in S. aureus but also impeded in vitro biofilm formation. The effect of AV73 on bacterial proteomes and extracellular protein levels were analyzed by quantitative proteomics and revealed a significant down-regulation of major virulence and biofilm promoting proteins...
February 16, 2018: Biochemistry
Abeje Ambaw, Lingxing Zheng, Mitali A Tambe, Katherine E Strathearn, Glen Acosta, Scott A Hubers, Fang Liu, Seth A Herr, Jonathan Tang, Alan Truong, Elwood Walls, Amber Pond, Jean-Christophe Rochet, Riyi Shi
Growing evidence suggests that oxidative stress plays a critical role in neuronal destruction characteristic of Parkinson's disease (PD). However, the molecular mechanisms of oxidative stress-mediated dopaminergic cell death are far from clear. In the current investigation, we tested the hypothesis that acrolein, an oxidative stress and lipid peroxidation (LPO) product, is a key factor in the pathogenesis of PD. Using a combination of in vitro, in vivo, and cell free models, coupled with anatomical, functional, and behavioral examination, we found that acrolein was elevated in 6-OHDA-injected rats, and behavioral deficits associated with 6-OHDA could be mitigated by the application of the acrolein scavenger hydralazine, and mimicked by injection of acrolein in healthy rats...
January 29, 2018: Molecular and Cellular Neurosciences
Jaime Felipe Guerrero-Garzón, Melisa Bénard-Valle, Rita Restano-Cassulini, Fernando Zamudio, Gerardo Corzo, Alejandro Alagón, Alejandro Olvera-Rodríguez
The three-finger toxins (3FTxs) represent an extremely diverse protein family in elapid venoms, where the short chain α-neurotoxins are the most relevant toxin group from the clinical point of view. Essentially, the 3FTxs variability and the low proportions of α-neurotoxins in the venoms of North American coral snakes make it difficult to obtain effective elapid antivenoms against the envenomation symptoms caused mainly by these α-neurotoxins. In this work, thirty 3FTx transcript sequences were obtained from the venom glands of four coral snake species from Mexico (M...
January 29, 2018: Biochimie
Regina Lamendella, Justin R Wright, Jada Hackman, Christopher McLimans, David R Toole, William Bernard Rubio, Rebecca Drucker, Hoi Tong Wong, Kate Sabey, John P Hegarty, David B Stewart
Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI...
January 2018: MSphere
Eugene Moore, Ryan Arvidson, Christopher Banks, Jean Urenda, Elizabeth Duong, Haroun Mohammad, Michael E Adams
The parasitoid wasp Ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach Periplaneta americana, inducing a seven to ten day lethargy termed hypokinesia. Hypokinesia presents as a significant reduction in both escape response and spontaneous walking. We examined aminergic and peptidergic components of milked venom with HPLC and MALDI-TOF mass spectrometry. HPLC coupled with electrochemical detection confirmed presence of dopamine in milked venom, while mass spectrometry revealed that the venom gland and venom sac have distinct peptide profiles, with milked venom predominantly composed of venom sac peptides...
January 19, 2018: Biochemistry
Imke Lueders, Carsten Ludwig, Johanna Kasberg, Christoph Georg Baums, Kerstin Klimke, Martin B Dorner, Dana Ströse, Volker Schmidt
Fatal clostridial infections and clostridial toxicoses are common in birds. Most fatalities are associated with toxin production and progress rapidly, often within 24 hours of infection. We describe an unusual and protracted course of disease in 6 captive brown pelicans ( Pelecanus occidentalis), which was believed to result from toxicosis by toxovar A produced by a mixed infection with Clostridium sordellii and Clostridium perfringens. Although the first death in the group occurred 3 days after signs of illness were documented, the remaining birds died over a 38-day period despite aggressive antibiotic and supportive therapy...
December 2017: Journal of Avian Medicine and Surgery
Richard J O'Callaghan
Staphylococcus aureus is a major pathogen of the eye able to infect the tear duct, eyelid, conjunctiva, cornea, anterior and posterior chambers, and the vitreous chamber. Of these infections, those involving the cornea (keratitis) or the inner chambers of the eye (endophthalmitis) are the most threatening because of their potential to cause a loss in visual acuity or even blindness. Each of these ocular sites is protected by the constitutive expression of a variety of antimicrobial factors and these defenses are augmented by a protective host response to the organism...
January 10, 2018: Pathogens
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
Kimbria J Blake, Pankaj Baral, Tiphaine Voisin, Ashira Lubkin, Felipe Almeida Pinho-Ribeiro, Kelsey L Adams, David P Roberson, Yuxin C Ma, Michael Otto, Clifford J Woolf, Victor J Torres, Isaac M Chiu
The hallmark of many bacterial infections is pain. The underlying mechanisms of pain during live pathogen invasion are not well understood. Here, we elucidate key molecular mechanisms of pain produced during live methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that spontaneous pain is dependent on the virulence determinant agr and bacterial pore-forming toxins (PFTs). The cation channel, TRPV1, mediated heat hyperalgesia as a distinct pain modality. Three classes of PFTs-alpha-hemolysin (Hla), phenol-soluble modulins (PSMs), and the leukocidin HlgAB-directly induced neuronal firing and produced spontaneous pain...
January 2, 2018: Nature Communications
Cédric Woudstra, Caroline Le Maréchal, Rozenn Souillard, Fabrizio Anniballi, Bruna Auricchio, Luca Bano, Marie-Hélène Bayon-Auboyer, Miriam Koene, Isabelle Mermoud, Roseane B Brito, Francisco C F Lobato, Rodrigo O S Silva, Martin B Dorner, Patrick Fach
Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C...
December 26, 2017: Anaerobe
Kin Ying Wong, Choo Hock Tan, Kae Yi Tan, Quraishi H Naeem, Nget Hong Tan
Naja naja is a medically important species that is distributed widely in South Asia. Its venom lethality and neutralization profile have been reported to vary markedly, but the understanding of this phenomenon has been limited without a comprehensive venom profile for the Pakistani N. naja. This study set to investigate the venom proteome of Pakistani N. naja applying reverse-phase HPLC, SDS-PAGE, mass spectrometry and data-mining approaches. The venom enzymatics and antigen binding activities were also studied...
December 23, 2017: Journal of Proteomics
Byung Eui Kim, Elena Goleva, Clifton F Hall, Sang Hyun Park, Un Ha Lee, Anne M Brauweiler, Joanne E Streib, Brittany N Richers, Gwuicheol Kim, Donald Y M Leung
In chronic non-healing wounds, the healing process is disrupted and wounds are often infected with bacteria. About 85% of lower extremity amputations in diabetes are attributed to deep infection of foot ulcers. Therefore, infection control is critical for wound care. In this study, we analyzed lipid composition of Chamaecyparis (C) obtusa extract, and describe the wound healing properties of its combination of ten major lipid components. A 10 lipid mixture upregulated HBD-3 and LL-37 through the olfactory receptor 2AT4, and induced phosphorylation of extracellular signal-regulated kinases and p38 mitogen-activated protein kinases in primary human keratinocytes...
December 22, 2017: Journal of Investigative Dermatology
Yonglin Zhou, Chengzhen Chen, Juan Pan, Xuming Deng, Jianfeng Wang
Staphylococcus aureus (S. aureus) is a common cause of hospital-acquired infection and has become an epidemic globally. Alpha-haemolysin (α-haemolysin), a pore-forming toxin, is one of the most important virulence factors secreted by most S. aureus strains. α-haemolysin monomers form a 232.4-kDa membrane-inserted heptamer by self-assembling to cause host cell lysis and death. Consequently, α-haemolysin plays a significant role in the pathogenesis of S. aureus, and it could be the target for the treatment of staphylococcal infection...
December 19, 2017: Microbial Pathogenesis
Flávia de Faria Siqueira, Rodrigo Otávio Silveira Silva, Anderson Oliveira do Carmo, Bárbara Bruna Ribeiro de Oliveira Mendes, Carolina Campolina Rebello Horta, Francisco Carlos Faria Lobato, Evanguedes Kalapothakis
Clostridium perfringens alpha toxin, encoded by plc gene, has been implicated in gas gangrene, a life threatening infection. Vaccination is considered one of the best solutions against Clostridium infections. Although studies have identified many low quality clostridial vaccines, the use of recombinant proteins has been considered a promising alternative. Previously, a naturally occurring alpha toxin isoform (αAV1b) was identified with a mutation at residue 11 (His/Tyr), which can affect its enzymatic activity...
December 12, 2017: Anaerobe
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