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toxin antitoxin

Gang Li, Mengyu Shen, Shuai Le, Yinling Tan, Ming Li, Xia Zhao, Wei Shen, Yuhui Yang, Jing Wang, Hongbin Zhu, Shu Li, Xiancai Rao, Fuquan Hu, Shuguang Lu
As a third-generation sequencing method, single-molecule real-time (SMRT) technology provides long read length, and it is well suited for re-sequencing projects and de novo assembly. In this study, Pseudomonas aeruginosa PA1 was characterized and re-sequenced using SMRT technology. PA1 was also subjected to genomic, comparative, and pan-genomic analyses. The multi-drug resistant strain PA1 possesses a 6,498,072 bp genome and a sequence type of ST-782. The genome of PA1 was also visualized, and the results revealed the details of general genome annotations, virulence factors, regulatory proteins, secretion system proteins, type II toxin-antitoxin pairs, and genomic islands...
October 20, 2016: Bioscience Reports
Mária Džunková, Giuseppe D'Auria, Hua Xu, Jun Huang, Yinghua Duan, Andrés Moya, Ciarán P Kelly, Xinhua Chen
Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials...
2016: Frontiers in Cellular and Infection Microbiology
Zhenping Cao, M Guillermina Casabona, Holger Kneuper, James D Chalmers, Tracy Palmer
The type VII protein secretion system (T7SS) plays a critical role in the virulence of human pathogens including Mycobacterium tuberculosis and Staphylococcus aureus. Here, we report that the S. aureus T7SS secretes a large nuclease toxin, EsaD. The toxic activity of EsaD is neutralized during its biosynthesis through complex formation with an antitoxin, EsaG, which binds to its C-terminal nuclease domain. The secretion of EsaD is dependent on a further accessory protein, EsaE, that does not interact with the nuclease domain, but instead binds to the EsaD N-terminal region...
October 10, 2016: Nature Microbiology
Chetana Baliga, Raghavan Varadarajan, Nilesh Aghera
The existence of parallel pathways in the folding of proteins seems intuitive, yet remains controversial. We explore the folding kinetics of the homodimeric E. coli toxin CcdB using multiple optical probes and approaches. Kinetic studies performed as a function of protein and denaturant concentrations demonstrate that the folding of CcdB is a four-state process. The two intermediates populated during folding are present on parallel pathways. Both form by rapid association of the monomers in a diffusion limited manner and appear to be largely unstructured, as they are silent to the optical probes employed in the current study...
October 4, 2016: Biochemistry
Nathalie Goeders, Ray Chai, Bihe Chen, Andrew Day, George P C Salmond
Toxin-antitoxin (TA) systems are small genetic modules that encode a toxin (that targets an essential cellular process) and an antitoxin that neutralises or suppresses the deleterious effect of the toxin. Based on the molecular nature of the toxin and antitoxin components, TA systems are categorised into different types. Type III TA systems, the focus of this review, are composed of a toxic endoribonuclease neutralised by a non-coding RNA antitoxin in a pseudoknotted configuration. Bioinformatic analysis shows that the Type III systems can be classified into subtypes...
2016: Toxins
Joao Gatica, Vijay Tripathi, Stefan J Green, Célia M Manaia, Thomas Berendonk, Damiano Cacace, Christophe Merlin, Norbert Kreuzinger, Thomas Schwartz, Despo Fatta-Kassinos, Luigi Rizzo, Carsten U Schwermer, Hemda Garelick, Edouard Jurkevitch, Eddie Cytryn
Integrons are extensively targeted as a proxy for anthropogenic impact in the environment. We developed a novel high-throughput amplicon sequencing pipeline that enables characterization of thousands of integron gene cassette-associated reads, and applied it to acquire a comprehensive overview of gene cassette composition in effluents from wastewater treatment facilities across Europe. Between 38,100 and 172,995 reads per-sample were generated and functionally characterized by screening against nr, SEED, ARDB and β-lactamase databases...
September 30, 2016: Environmental Science & Technology
Kit-Ling Fan, Yan-Li Wang, Gary Chu, Ling-Pong Leung
BACKGROUND: Injection of botulinum toxin type A for cosmetic purposes is common. It is believed to be safe, but adverse reactions have been reported, including dysphagia, generalized paralysis, respiratory depression, and death caused by focal injection of the toxin. Early administration of antitoxin in patients with adverse reactions is the mainstay of management, but the time window for its clinical efficacy is not well defined. CASE REPORTS: Two female adult patients with clinical botulism after botulinum toxin type A injection are described...
September 26, 2016: Journal of Emergency Medicine
Kai Xia, Ning Zang, Junmei Zhang, Hong Zhang, Yudong Li, Ye Liu, Wei Feng, Xinle Liang
Acetobacter pasteurianus is the main starter in rice vinegar manufacturing due to its remarkable abilities to resist and produce acetic acid. Although several mechanisms of acetic acid resistance have been proposed and only a few effector proteins have been identified, a comprehensive depiction of the biological processes involved in acetic acid resistance is needed. In this study, iTRAQ-based quantitative proteomic analysis was adopted to investigate the whole proteome of different acidic titers (3.6, 7.1 and 9...
December 5, 2016: International Journal of Food Microbiology
Lauren R Walling, J Scott Butler
: Toxin-antitoxin (TA) systems are ubiquitous in bacteria and archaea, where they play a pivotal role in the establishment and maintenance of dormancy. Under normal growth conditions, the antitoxin neutralizes the toxin. However, under conditions of stress, such as nutrient starvation or antibiotic treatment, cellular proteases degrade the antitoxin, and the toxin functions to arrest bacterial growth. We characterized the specificity determinants of the interactions between VapB antitoxins and VapC toxins from nontypeable Haemophilus influenzae (NTHi) in an effort to gain a better understanding of how antitoxins control toxin activity and bacterial persistence...
September 26, 2016: Journal of Bacteriology
Kenn Gerdes
Bacteria form persisters, cells that are tolerant to multiple antibiotics and other types of environmental stress. Persister formation can be induced either stochastically in single cells of a growing bacterial ensemble, or by environmental stresses, such as nutrient starvation, in a subpopulation of cells. In many cases, the molecular mechanisms underlying persistence are still unknown. However, there is growing evidence that, in enterobacteria, both stochastically and environmentally induced persistence are controlled by the second messenger (p)ppGpp...
November 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Victoria I Verhoeve, Krit Jirakanwisal, Tadanobu Utsuki, Kevin R Macaluso
Crucial factors influencing the epidemiology of Rickettsia felis rickettsiosis include pathogenesis and transmission. Detection of R. felis DNA in a number of arthropod species has been reported, with characterized isolates, R. felis strain LSU and strain LSU-Lb, generated from the cat flea, Ctenocephalides felis, and the non-hematophagous booklouse, Liposcelis bostrychophila, respectively. While it is realized that strain influence on host biology varies, the rickettsial response to these distinct host environments remained undefined...
2016: PloS One
Yoav Gal, Anita Sapoznikov, Reut Falach, Sharon Ehrlich, Moshe Aftalion, Tamar Sabo, Chanoch Kronman
The plant-toxin ricin, is considered a biological threat agent of concern and is most toxic when inhaled. Pulmonary exposure to a lethal dose of ricin can be redressed by treatment with anti-ricin antibodies, however late antitoxin intervention is of limited efficacy. This limitation is associated with the overt lung damage, clinically manifested as severe pulmonary inflammation, which develops over time. Increased evidence indicates that ciprofloxacin, a broad spectrum anti-microbial agent, possesses immunomodulatory properties...
September 19, 2016: Antimicrobial Agents and Chemotherapy
Kai Xia, Yudong Li, Jing Sun, Xinle Liang
Acetobacter pasteurianus, an acetic acid resistant bacterium belonging to alpha-proteobacteria, has been widely used to produce vinegar in the food industry. To understand the mechanism of its high tolerance to acetic acid and robust ability of oxidizing ethanol to acetic acid (> 12%, w/v), we described the 3.1 Mb complete genome sequence (including 0.28 M plasmid sequence) with a G+C content of 52.4% of A. pasteurianus Ab3, which was isolated from the traditional Chinese rice vinegar (Meiguichu) fermentation process...
2016: PloS One
Wai T Chan, Manuel Espinosa
Chromosomally encoded Type II Toxin-Antitoxin operons are ubiquitous in bacteria and archaea. Antitoxins neutralize the toxic effect of cognate Toxins by protein-protein interactions and sequestering the active residues of the Toxin. Toxins target essential bacterial processes, mostly translation and replication. However, one class apart is constituted by the PezAT pair because the PezT toxin target cell wall biosynthesis. Here, we have examined the role of the pezAT toxin-antitoxin genes in its natural host, the pathogenic bacterium Streptococcus pneumoniae...
2016: Frontiers in Microbiology
Jingsi Yang, Ke Zhou, Peng Liu, Yuhui Dong, Zengqiang Gao, Jianjun Zhang, Quansheng Liu
The toxin-antitoxin system is ubiquitously existed in bacteria and archaea, performing a wide variety of functions modulating cell fitness in response to environmental cues. In this report, we solved the crystal structure of the toxin-antitoxin HigBA complex from E. coli K-12 to 2.7 Å resolution. The crystal structure of the HigBA complex displays a hetero-tetramer (HigBA)2 form comprised by two HigB and two HigA subunits. Each toxin HigB resumes a microbial RNase T1 fold, characteristic of a three antiparallel β-sheet core shielded by a few α-helices at either side...
September 30, 2016: Biochemical and Biophysical Research Communications
Kristoffer Winther, Jai J Tree, David Tollervey, Kenn Gerdes
The major human pathogen Mycobacterium tuberculosis can survive in the host organism for decades without causing symptoms. A large cohort of Toxin-Antitoxin (TA) modules contribute to this persistence. Of these, 48 TA modules belong to the vapBC (virulence associated protein) gene family. VapC toxins are PIN domain endonucleases that, in enterobacteria, inhibit translation by site-specific cleavage of initiator tRNA. In contrast, VapC20 of M. tuberculosis inhibits translation by site-specific cleavage of the universally conserved Sarcin-Ricin loop (SRL) in 23S rRNA...
September 5, 2016: Nucleic Acids Research
Seema Patel
Despite the advent of next-generation sequencing (NGS) technologies, sophisticated data analysis and drug development efforts, bacterial drug resistance persists and is escalating in magnitude. To better control the pathogens, a thorough understanding of their genomic architecture and dynamics is vital. Bacterial genome is extremely complex, a mosaic of numerous co-operating and antagonizing components, altruistic and self-interested entities, behavior of which are predictable and conserved to some extent, yet largely dictated by an array of variables...
August 30, 2016: Infection, Genetics and Evolution
Christina E M Krämer, Wolfgang Wiechert, Dietrich Kohlheyer
Conventional propidium iodide (PI) staining requires the execution of multiple steps prior to analysis, potentially affecting assay results as well as cell vitality. In this study, this multistep analysis method has been transformed into a single-step, non-toxic, real-time method via live-cell imaging during perfusion with 0.1 μM PI inside a microfluidic cultivation device. Dynamic PI staining was an effective live/dead analytical tool and demonstrated consistent results for single-cell death initiated by direct or indirect triggers...
2016: Scientific Reports
Kevin T Huguet, Mathieu Gonnet, Benoît Doublet, Axel Cloeckaert
The multidrug resistance Salmonella Genomic Island 1 (SGI1) is an integrative mobilizable element identified in several enterobacterial pathogens. This chromosomal island requires a conjugative IncA/C plasmid to be excised as a circular extrachromosomal form and conjugally mobilized in trans. Preliminary observations suggest stable maintenance of SGI1 in the host chromosome but paradoxically also incompatibility between SGI1 and IncA/C plasmids. Here, using a Salmonella enterica serovar Agona clonal bacterial population as model, we demonstrate that a Toxin-Antitoxin (TA) system encoded by SGI1 plays a critical role in its stable host maintenance when an IncA/C plasmid is concomitantly present...
2016: Scientific Reports
Paulo Jardim, Isadora Cristina da Silva Santos, João Alexandre Ribeiro Gonçalves Barbosa, Sônia Maria de Freitas, Napoleão Fonseca Valadares
Persisters are individual bacterial cells that exhibit a phenotype characterized by slow growth, low metabolic rate and multidrug tolerance. The processes that drive cells into a persistence state constitute an active but incipient research field, and structural data regarding its components are scarce. The molecular targets of many therapeutic drugs are involved in cell wall synthesis and cell division, and these cellular processes are down-regulated in persister cells, consequently these cells are more likely to survive antibiotic treatment...
September 23, 2016: Biochemical and Biophysical Research Communications
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