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toxin antitoxin

Richard A Slayden, Clinton C Dawson, Jason E Cummings
There has been a significant reduction in annual tuberculosis incidence since the World Health Organization declared tuberculosis a global health threat. However, treatment of M. tuberculosis infections requires lengthy multidrug therapeutic regimens to achieve a durable cure. The development of new drugs that are active against resistant strains and phenotypically diverse organisms continues to present the greatest challenge in the future. Numerous phylogenomic analyses have revealed that the Mtb genome encodes a significantly expanded repertoire of toxin-antitoxin (TA) loci that makes up the Mtb TA system...
June 1, 2018: Pathogens and Disease
Eman Abdel Monaem Abdel Rashid, Nashwa Mohamed El-Mahdy, Huda Shehata Kharoub, Ahmed Salah Gouda, Naglaa Ahmed ElNabarawy, Bruno Mégarbane
Iatrogenic botulism resulting from the substantial increase in use of botulinum neurotoxin type-A (BoNT-A) treatment is rarely reported. We aimed to describe a large iatrogenic botulism outbreak in Egypt in June-July 2017. Nine patients developed botulism after receiving intramuscular injections of BoNT-A (dose: 200-300 IU) to treat cerebral palsy (N=7), spastic dystonia (N=1), and hyperhidrosis (N=1). Detailed findings were available in 5/9 cases. Patients were admitted to the hospital 5-10 days after the BoNT-A injection...
May 22, 2018: Basic & Clinical Pharmacology & Toxicology
Julian A Rycroft, Bridget Gollan, Grzegorz J Grabe, Alexander Hall, Angela M Cheverton, Gerald Larrouy-Maumus, Stephen A Hare, Sophie Helaine
Non-typhoidal Salmonella strains are responsible for invasive infections associated with high mortality and recurrence in sub-Saharan Africa, and there is strong evidence for clonal relapse following antibiotic treatment. Persisters are non-growing bacteria that are thought to be responsible for the recalcitrance of many infections to antibiotics. Toxin-antitoxin systems are stress-responsive elements that are important for Salmonella persister formation, specifically during infection. Here, we report the analysis of persister formation of clinical invasive strains of Salmonella Typhimurium and Enteritidis in human primary macrophages...
May 18, 2018: Nature Communications
Amita Gupta, Balaji Venkataraman, Madavan Vasudevan, Kiran Gopinath Bankar
A correction to this article has been published and is linked from the HTML and PDF version of this paper. The error has been fixed in the paper.
May 10, 2018: Scientific Reports
Mingxiang Li, Dennis Lee, Chidi R Obi, Joel K Freeberg, Shauna Farr-Jones, Milan T Tomic
Safe and effective antitoxins to treat and prevent botulism are needed for biodefense. We have developed recombinant antibody-based therapeutics for botulinum neurotoxin (BoNT) serotypes A, B, and E. The mechanism of action of this antitoxin requires that three mAbs bind one toxin molecule to achieve clearance. Here we present a co-formulation of an antitoxin to the three most important serotypes. Combining these antibodies obviates the need to identify the serotype causing intoxication prior to drug administration, which would facilitate administration...
2018: PloS One
Eleonora Mastrorilli, Daniele Pietrucci, Lisa Barco, Serena Ammendola, Sara Petrin, Alessandra Longo, Claudio Mantovani, Andrea Battistoni, Antonia Ricci, Alessandro Desideri, Carmen Losasso
Over the past decades, Salmonella 4,[5],12:i:- has rapidly emerged and it is isolated with high frequency in the swine food chain. Although many studies have documented the epidemiological success of this serovar, few investigations have tried to explain this phenomenon from a genetic perspective. Here a comparative whole-genome analysis of 50 epidemiologically unrelated S . 4,[5],12:i:-, isolated in Italy from 2010 to 2016 was performed, characterizing them in terms of genetic elements potentially conferring resistance, tolerance and persistence characteristics...
2018: Frontiers in Microbiology
Jean-Marc Cavaillon
Research on bacterial toxins is closely linked to the birth of immunology. Our understanding of the interaction of bacterial protein toxins with immune cells has helped to decipher immunopathology, develop preventive and curative treatments for infections, and propose anti-cancer immunotherapies. The link started when Behring and Kitasato demonstrated that serotherapy was effective against 'the strangling angel', namely diphtheria, and its dreadful toxin discovered by Roux and Yersin. The antitoxin treatment helped to save thousands of children...
April 1, 2018: Pathogens and Disease
Akanksha Nigam, Sathish Kumar, Hanna Engelberg-Kulka
mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "<u>e</u>xtracellular <u>d</u>eath <u>f</u>actors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules...
May 1, 2018: MBio
Julija Armalytė, Dukas Jurėnas, Renatas Krasauskas, Albinas Čepauskas, Edita Sužiedėlienė
Acinetobacter baumannii is one of the major causes of hard to treat multidrug-resistant hospital infections. A. baumannii features contributing to its spread and persistence in clinical environment are only beginning to be explored. Bacterial toxin-antitoxin (TA) systems are genetic loci shown to be involved in plasmid maintenance and proposed to function as components of stress response networks. Here we present a thorough characterization of type II system of A. baumannii , which is the most ubiquitous TA module present in A...
2018: Frontiers in Microbiology
Andrea Rocker, Madeleine Peschke, Tiia Kittilä, Roman Sakson, Clara Brieke, Anton Meinhart
Bacterial toxin-antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin-antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1...
April 27, 2018: Nature Communications
Nenad S Mitić, Saša N Malkov, Jovana J Kovačević, Gordana M Pavlović-Lažetić, Miloš V Beljanski
BACKGROUND: In the last decade and a half it has been firmly established that a large number of proteins do not adopt a well-defined (ordered) structure under physiological conditions. Such intrinsically disordered proteins (IDPs) and intrinsically disordered (protein) regions (IDRs) are involved in essential cell processes through two basic mechanisms: the entropic chain mechanism which is responsible for rapid fluctuations among many alternative conformations, and molecular recognition via short recognition elements that bind to other molecules...
April 25, 2018: BMC Bioinformatics
Chew Chieng Yeo
GCN5-related N-acetyltransferase (GNAT) is a huge superfamily of proteins spanning the prokaryotic and eukaryotic domains of life. GNAT proteins usually transfer an acetyl group from acetyl-CoA to a wide variety of substrates ranging from aminoglycoside antibiotics to large macromolecules. Type II toxin-antitoxin (TA) modules are typically bicistronic and widespread in bacterial and archael genomes with diverse cellular functions. Recently, a novel family of type II TA toxins was described which presents a GNAT-fold and functions by acetylating charged tRNA thereby precluding translation...
April 6, 2018: Molecular Microbiology
Helena Leinweber, Sulaiman M I Alotaibi, Søren Overballe-Petersen, Frank Hansen, Henrik Hasman, Valeria Bortolaia, Anette M Hammerum, Hanne Ingmer
The occurrence of vancomycin-resistant Enterococcus faecium (VREfm) in food has public health relevance since foodborne VREfm may colonize the gut of consumers and transfer vancomycin resistance genes to the indigenous gut microbiota. Therefore, we determined occurrence and elucidated genetic traits of VREfm in Danish retail chicken meat. Three out of 40 samples (7.5%) from two slaughterhouses yielded VREfm (vancomycin MIC > 32mg/L). This is the first report of VREfm in Danish retail poultry meat since 2010 (DANMAP)...
April 2, 2018: International Journal of Antimicrobial Agents
Simon Veyron, Gérald Peyroche, Jacqueline Cherfils
During the last decade, FIC proteins have emerged as a large family comprised of a variety of bacterial enzymes and a single member in animals. The air de famille of FIC proteins stems from a domain of conserved structure, which catalyzes the post-translational modification of proteins (PTM) by a phosphate-containing compound. In bacteria, examples of FIC proteins include the toxin component of toxin/antitoxin modules, such as Doc-Phd and VbhT-VbhA, toxins secreted by pathogenic bacteria to divert host cell processes, such as VopS, IbpA and AnkX, and a vast majority of proteins of unknown functions...
March 1, 2018: Pathogens and Disease
Audrey Segura, Pauline Auffret, Delphine Bibbal, Marine Bertoni, Alexandra Durand, Grégory Jubelin, Monique Kérourédan, Hubert Brugère, Yolande Bertin, Evelyne Forano
Healthy cattle are the primary reservoir for O157:H7 Shiga toxin-producing E. coli responsible for human food-borne infections. Because farm environment acts as a source of cattle contamination, it is important to better understand the factors controlling the persistence of E. coli O157:H7 outside the bovine gut. The E. coli O157:H7 strain MC2, identified as a persistent strain in French farms, possessed the characteristics required to cause human infections and genetic markers associated with clinical O157:H7 isolates...
2018: Frontiers in Microbiology
Sabine Pellett, Marite Bradshaw, William H Tepp, Christina L Pier, Regina C M Whitemarsh, Chen Chen, Joseph T Barbieri, Eric A Johnson
Botulinum neurotoxin (BoNT) is the causative agent of botulism and a widely used pharmaceutical to treat a variety of neurological diseases. BoNTs are 150-kDa protein toxins organized into heavy chain (HC) and light chain (LC) domains linked by a disulfide bond. The HC selectively binds to neurons and aids cell entry of the enzymatically active LC. There are seven immunological BoNT serotypes (A to G); each serotype includes genetic variants, termed subtypes. Only two subtypes, BoNT/A1 and BoNT/B1, are currently used as therapeutics...
March 27, 2018: MBio
Bassam H Rimawi
Botulism is a life-threatening toxin mediated disease that often presents with a sudden rapid onset of paralysis of their skeletal muscles with subsequent respiratory compromise and sudden death. Given the natural physiological changes during pregnancy, pregnant women with botulism may experience a more exaggerated course and have worse outcomes compared to nonpregnant women. Medical providers caring for such patients should not only maintain a high level of suspicion for botulism, but administration of an antitoxin early in their care can help reduce morbidity and mortality, while awaiting confirmatory laboratory results...
March 25, 2018: Journal of Maternal-fetal & Neonatal Medicine
Nicholas J Vietri
PURPOSE OF REVIEW: Inhalational anthrax is a rare disease and Bacillus anthracis is a likely pathogen to be used in a biological attack. The lack of clinical experience with anthrax has led experts to develop treatment guidelines. These guidelines recommend anthrax antitoxin to be used in conjunction with antibiotics for the treatment of patients with systemic anthrax infection, yet there is still a lack of human or animal data to support this recommendation. RECENT FINDINGS: The U...
March 22, 2018: Current Opinion in Infectious Diseases
Vilma Pérez, Cristina Dorador, Verónica Molina, Carolina Yáñez, Martha Hengst
The Salar de Huasco is an evaporitic basin located in the Chilean Altiplano, which presents extreme environmental conditions for life, i.e. high altitude (3800 m.a.s.l.), negative water balance, a wide salinity range, high daily temperature changes and the occurrence of the highest registered solar radiation on the planet (> 1200 W m-2 ). This ecosystem is considered as a natural laboratory to understand different adaptations of microorganisms to extreme conditions. Rhodobacter, an anoxygenic aerobic phototrophic bacterial genus, represents one of the most abundant groups reported based on taxonomic diversity surveys in this ecosystem...
March 22, 2018: Antonie Van Leeuwenhoek
Ji-Li Zhao, Wei Liu, Wan-Ying Xie, Xu-Dong Cao, Li Yuan
Background: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the most common chronic infectious amphixenotic diseases worldwide. Prevention and control of TB are greatly difficult, due to the increase in drug-resistant TB, particularly multidrug-resistant TB. We speculated that there were some differences between drug-sensitive and drug-resistant MTB strains and that mazEF 3,6,9 toxin-antitoxin systems (TASs) were involved in MTB viability. This study aimed to investigate differences in viability, biofilm formation, and MazEF expression between drug-sensitive and drug-resistant MTB strains circulating in Xinjiang, China, and whether mazEF 3,6,9 TASs contribute to MTB viability under stress conditions...
2018: Infection and Drug Resistance
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