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toxin antitoxin

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https://www.readbyqxmd.com/read/29149596/rational-design-of-evolutionarily-stable-microbial-kill-switches
#1
Finn Stirling, Lisa Bitzan, Samuel O'Keefe, Elizabeth Redfield, John W K Oliver, Jeffrey Way, Pamela A Silver
The evolutionary stability of synthetic genetic circuits is key to both the understanding and application of genetic control elements. One useful but challenging situation is a switch between life and death depending on environment. Here are presented "essentializer" and "cryodeath" circuits, which act as kill switches in Escherichia coli. The essentializer element induces cell death upon the loss of a bi-stable cI/Cro memory switch. Cryodeath makes use of a cold-inducible promoter to express a toxin. We employ rational design and a toxin/antitoxin titering approach to produce and screen a small library of potential constructs, in order to select for constructs that are evolutionarily stable...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29133571/development-of-protective-immunity-in-new-zealand-white-rabbits-challenged-with-bacillus-anthracis-spores-and-treated-with-antibiotics-and-obiltoxaximab-a-monoclonal-antibody-against-protective-antigen
#2
Lisa N Henning, Sarah Carpenter, Gregory V Stark, Natalya V Serbina
Recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax Protective Antigen (PA) is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for treatment of inhalational anthrax. Because of spore latency, disease re-emergence after treatment cessation is a concern and there is a need to understand development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29114057/directed-evolution-of-secb-chaperones-toward-toxin-antitoxin-systems
#3
Ambre Julie Sala, Patricia Bordes, Sara Ayala, Nawel Slama, Samuel Tranier, Michèle Coddeville, Anne-Marie Cirinesi, Marie-Pierre Castanié-Cornet, Lionel Mourey, Pierre Genevaux
SecB chaperones assist protein export in bacteria. However, certain SecB family members have diverged to become specialized toward the control of toxin-antitoxin (TA) systems known to promote bacterial adaptation to stress and persistence. In such tripartite TA-chaperone (TAC) systems, the chaperone was shown to assist folding and to prevent degradation of its cognate antitoxin, thus facilitating inhibition of the toxin. Here, we used both the export chaperone SecB of Escherichia coli and the tripartite TAC system of Mycobacterium tuberculosis as a model to investigate how generic chaperones can specialize toward the control of TA systems...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29109187/homologous-vapc-toxins-inhibit-translation-and-cell-growth-by-sequence-specific-cleavage-of-trna-fmet
#4
Lauren R Walling, J Scott Butler
Type II toxin-antitoxin (TA) systems play a critical role in the establishment and maintenance of bacterial dormancy. They are composed of a protein toxin and its cognate protein antitoxin. They function to regulate growth during conditions of stress, such as starvation or antibiotic treatment. As cellular proteases degrade the antitoxin, which normally binds and neutralizes the toxin, this frees the toxin to act on its cellular targets and arrest bacterial growth. TA systems are of particular concern in pathogenic organisms such as nontypeable Haemophilus influenzae (NTHi), as dormancy may lead to chronic infections and failure of antibiotic treatment...
November 6, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/29106666/tadb-2-0-an-updated-database-of-bacterial-type-ii-toxin-antitoxin-loci
#5
Yingzhou Xie, Yiqing Wei, Yue Shen, Xiaobin Li, Hao Zhou, Cui Tai, Zixin Deng, Hong-Yu Ou
TADB2.0 (http://bioinfo-mml.sjtu.edu.cn/TADB2/) is an updated database that provides comprehensive information about bacterial type II toxin-antitoxin (TA) loci. Compared with the previous version, the database refined and the new data schema is employed. With the aid of text mining and manual curation, it recorded 6193 type II TA loci in 870 replicons of bacteria and archaea, including 105 experimentally validated TA loci. In addition, the newly developed tool TAfinder combines the homolog searches and the operon structure detection, allowing the prediction for type II TA pairs in bacterial genome sequences...
November 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29099338/messing-up-translation-from-the-start-how-atat-inhibits-translation-initiation-in-e-coli
#6
Laurence Van Melderen, Dukas Jurenas, Abel Garcia-Pino
Toxin---antitoxin systems (TA) are widespread in bacteria and archea. They are commonly found in chromosomes and mobile genetic elements. These systems move from different genomic locations and bacterial hosts through horizontal gene transfer, using mobile elements as vehicles. Their potential roles in bacterial physiology are still a matter of debate in the field. The mechanisms of action of different toxin families have been deciphered at the molecular level. Intriguingly, the vast majority of these toxins target protein synthesis...
November 3, 2017: RNA Biology
https://www.readbyqxmd.com/read/29089929/fic-proteins-of-campylobacter-fetus-subsp-venerealis-form-a-network-of-functional-toxin-antitoxin-systems
#7
Hanna Sprenger, Sabine Kienesberger, Brigitte Pertschy, Lisa Pöltl, Bettina Konrad, Priya Bhutada, Dina Vorkapic, Denise Atzmüller, Florian Feist, Christoph Högenauer, Gregor Gorkiewicz, Ellen L Zechner
Enzymes containing the FIC (filamentation induced by cyclic AMP) domain catalyze post-translational modifications of target proteins. In bacteria the activity of some Fic proteins resembles classical toxin-antitoxin (TA) systems. An excess of toxin over neutralizing antitoxin can enable bacteria to survive some stress conditions by slowing metabolic processes and promoting dormancy. The cell can return to normal growth when sufficient antitoxin is present to block toxin activity. Fic genes of the human and animal pathogen Campylobacter fetus are significantly associated with just one subspecies, which is specifically adapted to the urogenital tract...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29073888/effective-and-rapid-treatment-of-wound-botulism-a-case-report
#8
M Schulte, U Hamsen, T A Schildhauer, T Ramczykowski
BACKGROUND: The latest news shows several cases of contaminated heroin that is found in different parts all over Europe. This information can be helpful for the emergency doctors to find the correct diagnosis of wound botulism in patients who are intravenous drug users. CASE PRESENTATION: We describe a case of a 40-year-old man who presented to the emergency department in 2016. He suffered from mild dysarthria, diplopia, dysphagia and ptosis since two days. The CT-scan of the cerebrum and the liquor were without any pathological results...
October 26, 2017: BMC Surgery
https://www.readbyqxmd.com/read/29073283/identification-of-novel-substrates-of-shigella-t3sa-through-analysis-of-its-virulence-plasmid-encoded-secretome
#9
Laurie Pinaud, Mariana L Ferrari, Robin Friedman, Nico Jehmlich, Martin von Bergen, Armelle Phalipon, Philippe J Sansonetti, François-Xavier Campbell-Valois
Many human Gram-negative bacterial pathogens express a Type Three Secretion Apparatus (T3SA), including among the most notorious Shigella spp., Salmonella enterica, Yersinia enterocolitica and enteropathogenic Escherichia coli (EPEC). These bacteria express on their surface multiple copies of the T3SA that mediate the delivery into host cells of specific protein substrates critical to pathogenesis. Shigella spp. are Gram-negative bacterial pathogens responsible for human bacillary dysentery. The effector function of several Shigella T3SA substrates has largely been studied but their potential cellular targets are far from having been comprehensively delineated...
2017: PloS One
https://www.readbyqxmd.com/read/29073136/a-bacterial-toxin-antitoxin-module-is-the-origin-of-inter-bacterial-and-inter-kingdom-effectors-of-bartonella
#10
Alexander Harms, Marius Liesch, Jonas Körner, Maxime Québatte, Philipp Engel, Christoph Dehio
Host-targeting type IV secretion systems (T4SS) evolved from conjugative T4SS machineries that mediate interbacterial plasmid transfer. However, the origins of effectors secreted by these virulence devices have remained largely elusive. Previous work showed that some effectors exhibit homology to toxins of bacterial toxin-antitoxin modules, but the evolutionary trajectories underlying these ties had not been resolved. We previously reported that FicT toxins of FicTA toxin-antitoxin modules disrupt cellular DNA topology via their enzymatic FIC (filamentation induced by cAMP) domain...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29066303/computational-insights-into-promoter-architecture-of-toxin-antitoxin-systems-of-mycobacterium-tuberculosis
#11
Zoozeal Thakur, Vandana Saini, Preeti Arya, Ajit Kumar, Promod K Mehta
Toxin-antitoxin (TA) systems are two component genetic modules widespread in many bacterial genomes, including Mycobacterium tuberculosis (Mtb). The TA systems play a significant role in biofilm formation, antibiotic tolerance and persistence of pathogen inside the host cells. Deciphering regulatory motifs of Mtb TA systems is the first essential step to understand their transcriptional regulation. In this study, in silico approaches, that is, the knowledge based motif discovery and de novo motif discovery were used to identify the regulatory motifs of 79 Mtb TA systems...
October 21, 2017: Gene
https://www.readbyqxmd.com/read/29057798/production-characterisation-and-testing-of-an-ovine-antitoxin-against-ricin-efficacy-potency-and-mechanisms-of-action
#12
Sarah J C Whitfield, Gareth D Griffiths, Dominic C Jenner, Robert J Gwyther, Fiona M Stahl, Lucy J Cork, Jane L Holley, A Christopher Green, Graeme C Clark
Ricin is a type II ribosome-inactivating toxin that catalytically inactivates ribosomes ultimately leading to cell death. The toxicity of ricin along with the prevalence of castor beans (its natural source) has led to its increased notoriety and incidences of nefarious use. Despite these concerns, there are no licensed therapies available for treating ricin intoxication. Here, we describe the development of a F(ab')₂ polyclonal ovine antitoxin against ricin and demonstrate the efficacy of a single, post-exposure, administration in an in vivo murine model of intoxication against aerosolised ricin...
October 18, 2017: Toxins
https://www.readbyqxmd.com/read/29056932/pathogenicity-of-human-st23-streptococcus-agalactiae-to-fish-and-genomic-comparison-of-pathogenic-and-non-pathogenic-isolates
#13
Rui Wang, Liping Li, Yin Huang, Ting Huang, Jiayou Tang, Ting Xie, Aiying Lei, Fuguang Luo, Jian Li, Yan Huang, Yunliang Shi, Dongying Wang, Ming Chen, Qiang Mi, Weiyi Huang
Streptococcus agalactiae, or Group B Streptococcus (GBS), is a major pathogen causing neonatal sepsis and meningitis, bovine mastitis, and fish meningoencephalitis. CC23, including its namesake ST23, is not only the predominant GBS strain derived from human and cattle, but also can infect a variety of homeothermic and poikilothermic species. However, it has never been characterized in fish. This study aimed to determine the pathogenicity of ST23 GBS to fish and explore the mechanisms causing the difference in the pathogenicity of ST23 GBS based on the genome analysis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29046006/-skin-and-soft-tissue-infections-due-to-corynebacterium-ulcerans-case-reports
#14
Christian Jenssen, Ilona Schwede, Volker Neumann, Cristine Pietsch, Werner Handrick
History and clinical findings We report on three patients suffering from skin and soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans strains. In all three patients, there was a predisposition due to chronic diseases. Three patients had domestic animals (cat, dog) in their households. Investigations and diagnosis A mixed bacterial flora including Corynebacterium ulcerans was found in wound swab samples. Diphtheric toxin was produced by the Corynebacterium ulcerans strains in all three cases...
October 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29044211/identification-of-novel-mazef-pemik-family-toxin-antitoxin-loci-and-their-distribution-in-the-staphylococcus-genus
#15
Michal Bukowski, Karolina Hyz, Monika Janczak, Marcin Hydzik, Grzegorz Dubin, Benedykt Wladyka
The versatile roles of toxin-antitoxin (TA) systems in bacterial physiology and pathogenesis have been investigated for more than three decades. Diverse TA loci in Bacteria and Archaea have been identified in genome-wide studies. The advent of massive parallel sequencing has substantially expanded the number of known bacterial genomic sequences over the last 5 years. In staphylococci, this has translated into an impressive increase from a few tens to a several thousands of available genomes, which has allowed us for the re-evalution of prior conclusions...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030445/microhomology-mediated-high-throughput-gene-inactivation-strategy-for-hyperthermophilic-crenarchaeon-sulfolobus-islandicus
#16
Changyi Zhang, Rachel J Whitaker
Sulfolobus islandicus is rapidly emerging as a model system for studying the biology and evolution within the TACK lineage of the Archaeal domain. As the tree of life grows, identifying the cellular function of genes within this lineage will have significant impacts on our understanding of the evolution of Last Archaeal Eukaryote Common Ancestor (LEACA) and the differentiation of Archaea from Eukaryotes during the evolution of the modernday cell. To progress our understanding of this key Archaeal organism, we report a novel high-throughput method for targeted gene inactivation in S...
October 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28993337/whole-transcriptome-and-genomic-analysis-of-extensively-drug-resistant-mycobacterium-tuberculosis-clinical-isolates-identifies-downregulation-of-etha-as-a-mechanism-of-ethionamide-resistance
#17
Lynne de Welzen, Vegard Eldholm, Kashmeel Maharaj, Abigail L Manson, Ashlee M Earl, Alexander S Pym
Genetic based drug susceptibility testing has improved the diagnosis of drug-resistant tuberculosis, but is limited by our lack of knowledge of all resistance mechanisms. Next generation sequencing has assisted in identifying the principal genetic mechanisms of resistance for many drugs, but a significant proportion of phenotypic drug resistance is unexplained genetically. Few studies have formally compared the transcriptome of susceptible and resistant M. tuberculosis We carried out comparative whole genome transcriptomics on extensively drug-resistant (XDR) clinical isolates using RNA-sequencing (RNAseq) to find novel transcriptional mediated mechanisms of resistance...
October 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28986943/crystal-structure-of-mycobacterium-tuberculosis-vapc20-toxin-and-its-interactions-with-cognate-antitoxin-vapb20-suggest-a-model-for-toxin-antitoxin-assembly
#18
Amar Deep, Soni Kaundal, Sakshi Agarwal, Ramandeep Singh, Krishan Gopal Thakur
VapBCs, virulence-associated proteins, are the most abundant type II toxin-antitoxin (TA) systems in prokaryotes. Under normal conditions, toxin and antitoxin interact to form a heterooctameric complex, which upon binding to operator sites, inhibits their own expression. Under stress conditions, the VapB antitoxin is degraded by cellular proteases to release a free VapC toxin, which in turn inhibits cell growth mainly by targeting protein translation. However, the intermediate steps involved in the assembly of the heterooctameric complex have not been resolved...
October 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28985291/mobile-genetic-elements-and-evolution-of-crispr-cas-systems-all-the-way-there-and-back
#19
Eugene V Koonin, Kira S Makarova
The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci...
October 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28979246/variable-persister-gene-interactions-with-p-ppgpp-for-persister-formation-in-escherichia-coli
#20
Shuang Liu, Nan Wu, Shanshan Zhang, Youhua Yuan, Wenhong Zhang, Ying Zhang
Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA) system HipAB depends on stringent response effector (p)ppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (p)ppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ) using Escherichia coli as a model...
2017: Frontiers in Microbiology
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