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toxin antitoxin

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https://www.readbyqxmd.com/read/28445136/selective-eradication-of-cancer-cells-by-delivery-of-adenovirus-based-toxins
#1
Shiran Shapira, Assaf Shapira, Diana Kazanov, Gil Hevroni, Sarah Kraus, Nadir Arber
BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430938/characterization-of-yjjj-toxin-of-escherichia-coli
#2
Yuki Maeda, Chun-Yi Lin, Yojiro Ishida, Masayori Inouye, Yoshihiro Yamaguchi, Sangita Phadtare
Reminiscent of eukaryotic apoptotic programmed cell death, bacteria also contain a large number of suicide genes, which are in general co-expressed with their cognate antitoxic genes. These systems called the toxin-antitoxin (TA) systems are associated with cellular dormancy, and play major roles in biofilm formation and persistent multi-drug resistance of many human pathogens. In recent years, the study on TA system toxins has become a hot topic due to the health implications of these toxins by virtue of their role in bacterial pathogenicity...
April 19, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28420090/toxins-of-prokaryotic-toxin-antitoxin-systems-with-sequence-specific-endoribonuclease-activity
#3
REVIEW
Hisako Masuda, Masayori Inouye
Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA containing recognition sequences in the absence of ribosome in vitro. However, increasing evidence suggests that in vivo digestion may occur in association with ribosomes...
April 14, 2017: Toxins
https://www.readbyqxmd.com/read/28419869/allodemic-distribution-of-plasmids-co-harbouring-blactx-m-15-aac-6-ib-cr-qnrb-in-klebsiella-pneumoniae-is-the-main-source-of-extended-spectrum-%C3%AE-lactamases-in-uruguay-s-paediatric-hospital
#4
V Garcia-Fulgueiras, L Araujo, I Bado, N F Cordeiro, M I Mota, G Laguna, G Algorta, R Vignoli
OBJECTIVES: This study aimed to describe the characteristics of clinical isolates of extended-spectrum β-lactamase (ESBL)-producing enterobacteria (EPE) in Uruguay's paediatric hospital. METHODS: ESBLs, qnr alleles and aac(6')-Ib-cr were sought and characterised in EPE isolated between March 2010 and March 2012. Transfer of resistance determinants was assessed by conjugation. Incompatibility (Inc) groups, plasmid toxin-antitoxin systems (TAS) and plasmid size were determined in transconjugants...
April 15, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28393877/comprehensive-mapping-of-the-helicobacter-pylori-nikr-regulon-provides-new-insights-in-bacterial-nickel-responses
#5
Andrea Vannini, Eva Pinatel, Paolo Emidio Costantini, Simone Pelliciari, Davide Roncarati, Simone Puccio, Gianluca De Bellis, Clelia Peano, Alberto Danielli
Nickel homeostasis is important for pathogenic and ureolytic bacteria, which use this metal ion as enzymatic cofactor. For example, in the human pathogen Helicobacter pylori an optimal balance between nickel uptake and incorporation in metallo-enzymes is fundamental for colonization of the host. Nickel is also used as cofactor to modulate DNA binding of the NikR regulator, which controls transcription of genes involved in nickel trafficking or infection in many bacteria. Accordingly, there is much interest in a systematic characterization of NikR regulation...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28369041/atat-blocks-translation-initiation-by-n-acetylation-of-the-initiator-trna-fmet
#6
Dukas Jurėnas, Sneha Chatterjee, Albert Konijnenberg, Frank Sobott, Louis Droogmans, Abel Garcia-Pino, Laurence Van Melderen
Toxin-antitoxin (TA) loci are prevalent in bacterial genomes. They are suggested to play a central role in dormancy and persister states. Under normal growth conditions, TA toxins are neutralized by their cognate antitoxins, and under stress conditions, toxins are freed and inhibit essential cellular processes using a variety of mechanisms. Here we characterize ataR-ataT, a novel TA system, from enterohemorrhagic Escherichia coli. We show that the toxin AtaT is a GNAT family enzyme that transfers an acetyl group from acetyl coenzyme A to the amine group of the methionyl aminoacyl moiety of initiator tRNA...
April 3, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28360447/botulism-outbreak-in-a-family-after-ingestion-of-locally-produced-cheese
#7
Shahram Rafie, Shokrollah Salmanzadeh, Asieh Mehramiri, Adel Nejati
Botulism is one of the most important foodborne diseases and is caused by Clostridium botulinum toxin. The main manifestations are flaccid muscle paralysis and cranial nerve palsies. Botulism is an essential health problem because of its high mortality. The diagnosis of botulism, especially in sporadic cases, is a medical challenge and a high clinical suspicion is necessary for early recognition. So, every physician should be familiar with its signs and symptoms for early detection and treatment. We describe a family with dysphasia and acute paralysis after the ingestion of locally made cheese...
March 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28348028/examination-of-e-faecalis-toxin-antitoxin-ta-toxin-fst-function-utilizing-a-pheromone-inducible-expression-vector-with-tight-repression-and-large-dynamic-range
#8
Keith E Weaver, Yuqing Chen, Elly M Miiller, Jake N Johnson, Alex A Dangler, Dawn A Manias, Aaron M Clem, Daniel J Schjodt, Gary M Dunny
Tools for regulated gene expression in E. faecalis are extremely limited. In this study we describe the construction of an expression vector for E. faecalis, designated pCIE, utilizing the PQ pheromone-responsive promoter of plasmid pCF10. We demonstrate that this promoter is tightly repressed, responds to nanogram quantities of the peptide pheromone, and has a large dynamic range. To demonstrate its utility, the promoter was used to control expression of the toxic peptides of two par family toxin-antitoxin loci present in E...
March 27, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28347177/new-mechanistic-insights-into-the-motile-to-sessile-switch-in-various-bacteria-with-particular-emphasis-on-bacillus-subtilis-and-pseudomonas-aeruginosa-a-review
#9
Faizan A Sadiq, Steve Flint, Yun Li, TongJie Liu, Yuan Lei, Hafiz Arbab Sakandar, GuoQing He
A biofilm is a complex assemblage of microbial communities adhered to a biotic or an abiotic surface which is embedded within a self-produced matrix of extracellular polymeric substances. Many transcriptional regulators play a role in triggering a motile-sessile switch and in consequently producing the biofilm matrix. This review is aimed at highlighting the role of two nucleotide signaling molecules (c-di-GMP and c-di-AMP), toxin antitoxin modules and a novel transcriptional regulator BolA in biofilm formation in various bacteria...
April 2017: Biofouling
https://www.readbyqxmd.com/read/28338924/a-nonsynonymous-snp-catalog-of-mycobacterium-tuberculosis-virulence-genes-and-its-use-for-detecting-new-potentially-virulent-sublineages
#10
Natalya E Mikheecheva, Marina V Zaychikova, Alexander V Melerzanov, Valery N Danilenko
Mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an M. tuberculosis classification approach based on functional polymorphisms in virulence genes. An M. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin-antitoxin systems...
April 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28334932/ribosome-dependent-vibrio-cholerae-mrnase-higb2-is-regulated-by-a-%C3%AE-strand-sliding-mechanism
#11
San Hadži, Abel Garcia-Pino, Sarah Haesaerts, Dukas Jurenas, Kenn Gerdes, Jurij Lah, Remy Loris
Toxin-antitoxin (TA) modules are small operons involved in bacterial stress response and persistence. higBA operons form a family of TA modules with an inverted gene organization and a toxin belonging to the RelE/ParE superfamily. Here, we present the crystal structures of chromosomally encoded Vibrio cholerae antitoxin (VcHigA2), toxin (VcHigB2) and their complex, which show significant differences in structure and mechanisms of function compared to the higBA module from plasmid Rts1, the defining member of the family...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334797/molecular-mechanism-governing-ratio-dependent-transcription-regulation-in-the-ccdab-operon
#12
Alexandra Vandervelde, Igor Drobnak, San Hadži, Yann G-J Sterckx, Thomas Welte, Henri De Greve, Daniel Charlier, Rouslan Efremov, Remy Loris, Jurij Lah
Bacteria can become transiently tolerant to several classes of antibiotics. This phenomenon known as persistence is regulated by small genetic elements called toxin-antitoxin modules with intricate yet often poorly understood self-regulatory features. Here, we describe the structures of molecular complexes and interactions that drive the transcription regulation of the ccdAB toxin-antitoxin module. Low specificity and affinity of the antitoxin CcdA2 for individual binding sites on the operator are enhanced by the toxin CcdB2, which bridges the CcdA2 dimers...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334216/deletion-of-mazf-increases-staphylococcus-aureus-biofilm-formation-in-an-ica-dependent-manner
#13
Fuminori Kato, Yusuke Yabuno, Yoshihiro Yamaguchi, Motoyuki Sugai, Masayori Inouye
Toxin-antitoxin (TA) systems are composed of a toxin that inhibits an essential cellular process (e.g., DNA replication, transcription, membrane integrity) and its cognate antitoxin that neutralizes the effect of the toxin. Staphylococcus aureus harbors two types of chromosomally encoded TA systems, namely mazEFsa encoding a UACAU-specific mRNA interferase and two paralogous genes of yefM-yoeBsa encoding a ribosome-dependent endoribonuclease system. However, little is known about the physiological role of MazEFsa and YefM-YoeBsa in S...
March 8, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28320039/the-role-of-peganum-harmala-ethanolic-extract-and-type-ii-toxin-antitoxin-system-in-biofilm-formation
#14
Nasrin Valizadeh, Firuzeh Valian, Nourkhoda Sadeghifard, Shahriar Karami, Iraj Pakzad, Hossein Kazemian, Sobhan Ghafourian
Toxin antitoxin system is a regulatory system that antitoxin inhibits the toxin. We aimed to determine the role of TA loci in biofilm formation in K. pneumoniae clinical and environmental isolates; also inhibition of biofilm formation by Peganum harmala. So, 40 K. pneumoniae clinical and environmental isolates were subjected for PCR to determine the frequency of mazEF, relEB, and mqsRA TA loci. Biofilm formation assay subjected for all isolates. Then, P. harmala was tested against positive biofilm formation strains...
March 20, 2017: Drug Research
https://www.readbyqxmd.com/read/28303133/corrigendum-what-is-the-link-between-stringent-response-endoribonuclease-encoding-type-ii-toxin-antitoxin-systems-and-persistence
#15
Bhaskar C M Ramisetty, Dimpy Ghosh, Moumita Roy Chowdhury, Ramachandran S Santhosh
[This corrects the article on p. 1882 in vol. 7, PMID: 27933045.].
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28298445/the-structure-and-function-of-mycobacterium-tuberculosis-mazf-mt6-provides-insights-into-conserved-features-of-mazf-endonucleases
#16
Eric D Hoffer, Stacey J Miles, Christine M Dunham
Toxin-antitoxin systems are ubiquitous in prokaryotic and archaea genomes and regulate growth in response to stress. E. coli contains at least 36 putative toxin-antitoxin gene pairs, and some pathogens such as Mycobacterium tuberculosis (Mtb) have over 90 toxin-antitoxin operons. E. coli MazF cleaves free mRNA after encountering stress and nine Mtb MazF family members cleave mRNA, tRNA, or rRNA. Moreover, Mtb MazF-mt6 cleaves 23S rRNA Helix 70 to inhibit protein synthesis. The overall tertiary folds of these MazFs are predicted to be similar, therefore it is unclear how they recognize structurally distinct RNAs...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28292710/bacterial-persistence-from-a-system-level-perspective
#17
REVIEW
Jakub Leszek Radzikowski, Hannah Schramke, Matthias Heinemann
In recent years, our understanding about bacterial persistence has significantly advanced: we comprehend the persister phenotype better, more triggers for persistence entry have been found, and more insights in the involvement and role of toxin-antitoxin systems and other molecular mechanisms have been unravelled. In this review, we attempt to put these findings into an integrated, system-level perspective. From this point of view, persistence can be seen as a response to a strong perturbation of metabolic homeostasis, either triggered environmentally, or by means of intracellular stochasticity...
March 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28282873/crystal-structure-of-the-receptor-binding-domain-of-botulinum-neurotoxin-type-ha-also-known-as-type-fa-or-h
#18
Guorui Yao, Kwok-Ho Lam, Kay Perry, Jasmin Weisemann, Andreas Rummel, Rongsheng Jin
Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently...
March 8, 2017: Toxins
https://www.readbyqxmd.com/read/28280011/draft-genome-sequence-of-agrococcusbaldri-strain-marseille-p2731
#19
Pamela Afouda, Gregory Dubourg, Noemie Labas, Didier Raoult, Pierre-Edouard Fournier
Agrococcus baldri strain Marseille-P2731 was isolated from a Siberian permafrost specimen dated around 10 million years. The 3,021,022-bp genome of strain Marseille-P2731, with a 71.82% G+C content, includes 2,844 protein-coding genes, 72 toxin/antitoxin modules, nine bacteriocin-encoding genes, and 1,266 genes associated with mobilome.
March 9, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28279904/toxin-antitoxin-systems-reversible-toxicity
#20
REVIEW
Alexander Mj Hall, Bridget Gollan, Sophie Helaine
Toxin-antitoxin (TA) systems encoded on the plasmids and chromosomes of bacteria are emerging as key players in stress adaptation. In particular, they have been implicated in the induction of persisters non-growing cells that can evade antibiotic exposure. TA toxins operate by a diverse range of mechanisms, either destructive or conservative, leading to the reversible growth arrest of bacterial cells. Whilst the molecular mechanisms of intoxication are now well understood, we still have very little information on how corrupted cells reawaken...
March 6, 2017: Current Opinion in Microbiology
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