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toxin and antitoxin

Qiangde Duan, Ti Lu, Carolina Garcia, Coraima Yañez, Rahul M Nandre, David A Sack, Weiping Zhang
Enterotoxigenic Escherichia coli (ETEC) bacteria remain a leading cause of children's diarrhea and travelers' diarrhea. Vaccines that induce antibodies to block ETEC bacterial adherence and to neutralize toxin enterotoxicity can be effective against ETEC-associated diarrhea. Recent studies showed that 6xHis-tagged CFA/I/II/IV multiepitope fusion antigen (MEFA) induced broad-spectrum antibodies to inhibit adherence of the seven most important ETEC adhesins (CFA/I, CS1 to CS6) (Ruan et al., 2014a) and 6xHis-tagged toxoid fusion antigen 3xSTaN12S -mnLTR192G/L211A (previously named as 3xSTaN12S -dmLT) elicited antibodies to neutralize both heat-labile toxin (LT) and heat-stable toxin (STa) produced by ETEC strains (Ruan et al...
2018: Frontiers in Microbiology
Sooyeon Song, Thomas K Wood
No abstract text is available yet for this article.
2018: Frontiers in Microbiology
Huynh Thi Loan, Lam Minh Yen, Evelyne Kestelyn, Nguyen Van Hao, Nguyen Thi Hoang Mai, Duong Bich Thuy, Ha Thi Hai Duong, Nguyen Thi Phuong Dung, Nguyen Hoan Phu, Pham Thi Lieu, Tran Tan Thanh, Ronald Geskus, H Rogier van Doorn, Le Van Tan, Duncan Wyncoll, Nicholas P J Day, Tran Tinh Hien, Guy E Thwaites, Nguyen Van Vinh Chau, C Louise Thwaites
Tetanus remains a significant burden in many low- and middle-income countries. The tetanus toxin acts within the central nervous system and intrathecal antitoxin administration may be beneficial, but there are safety concerns, especially in resource-limited settings. We performed a pilot study to assess the safety and feasibility of intrathecal human tetanus immunoglobulin in five adults with tetanus before the conduct of a large randomized controlled trial. Intrathecal injection via lumbar puncture was given to all patients within a median 140 (range 100-165) minutes of intensive care unit (ICU) admission...
June 18, 2018: American Journal of Tropical Medicine and Hygiene
A Bouam, N Armstrong, A Levasseur, M Drancourt
Three slowly growing mycobacteria named strain AB308, strain AB215 and strain AB57 were isolated from the tomato plant roots. The 16S rRNA and rpoB gene sequence analyses suggested that each strain was representative of one hitherto unidentified slowly-growing Mycobacterium species of the Mycobacterium simiae complex. Genome sequencing indicated that each strain contained one chromosome of 6.015-6.029 Mbp. A total of 1,197, 1,239 and 1,175 proteins were found to be associated with virulence and 107, 76 and 82 proteins were associated with toxin/antitoxin systems for strains AB308, AB215 and AB57, respectively...
June 18, 2018: Scientific Reports
Wendy W K Mok, Mark P Brynildsen
Bacterial persisters are subpopulations of phenotypic variants in isogenic cultures that can survive lethal doses of antibiotics. Their tolerances are often attributed to reduced activities of antibiotic targets, which limit corruption and damage in persisters compared with bacteria that die from treatment. However, that model does not hold for nongrowing populations treated with ofloxacin, a fluoroquinolone, where antibiotic-induced damage is comparable between cells that live and those that die. To understand how those persisters achieve this feat, we employed a genetic system that uses orthogonal control of MazF and MazE, a toxin and its cognate antitoxin, to generate model persisters that are uniformly tolerant to ofloxacin...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rashad Alkasir, Yanan Ma, Fei Liu, Jing Li, Na Lv, Yong Xue, Yongfei Hu, Baoli Zhu
Acinetobacter baumannii is a nonfermenting Gram-negative bacillus. A. baumannii resistance is a significant obstacle to clinical infection treatment. The existence of persister cells (persisters) might represent the reason for therapy failure and relapse, and such cells may be the driving force behind rising resistance rates. In this study, A. baumannii ATCC 19606 was used as a target to explore the essential features of A. baumannii persisters. Antibiotic treatment of A. baumannii cultures at 50-fold the minimum inhibitory concentration resulted in a distinct plateau of surviving drug-tolerant persisters...
June 14, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Frédéric Goormaghtigh, Nathan Fraikin, Marta Putrinš, Thibaut Hallaert, Vasili Hauryliuk, Abel Garcia-Pino, Andreas Sjödin, Sergo Kasvandik, Klas Udekwu, Tanel Tenson, Niilo Kaldalu, Laurence Van Melderen
Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to play a key role in the formation of persister cells in Escherichia coli based on the observation that successive deletions of TA systems decreased persistence frequency. In addition, the model proposed that stochastic fluctuations of (p)ppGpp levels are the basis for triggering activation of TA systems...
June 12, 2018: MBio
Behrooz Sadeghi Kalani, Gholamreza Irajian, Lida Lotfollahi, Esmail Abdollahzadeh, Shabnam Razavi
Listeria monocytogenes is known as a major food-borne pathogen causing a severe life-threatening disease, listeriosis, in susceptible patients. This bacterium has special features that facilitate its survival in different conditions and cause resistance to antibacterial agents and biocides. Toxin-antitoxin (TA) system has a potential to be introduced as an antibacterial target because of its participation in cell physiology, including stress response, antiphage activity, biofilm formation, and resistance to antibiotics...
June 4, 2018: Microbial Pathogenesis
Do-Hee Kim, Sung-Min Kang, Sung Jean Park, Chenglong Jin, Hye-Jin Yoon, Bong-Jin Lee
Streptococcus pneumonia has attracted increasing attention due to its resistance to existing antibiotics. TA systems are essential for bacterial persistence under stressful conditions such as nutrient deprivation, antibiotic treatment, and immune system attacks. In particular, S. pneumoniae expresses the HicBA TA gene, which encodes the stable HicA toxin and the labile HicB antitoxin. These proteins interact to form a non-toxic TA complex under normal conditions, but the toxin is activated by release from the antitoxin in response to unfavorable growth conditions...
June 6, 2018: Nucleic Acids Research
Peter H Culviner, Michael T Laub
Toxin-antitoxin systems are widely distributed genetic modules that regulate growth and persistence in bacteria. Many systems, including E. coli MazEF, include toxins that are endoribonucleases, but the full set of targets for these toxins remains poorly defined. Previous studies on a limited set of transcripts suggested that MazF creates a pool of leaderless mRNAs that are preferentially translated by specialized ribosomes created through MazF cleavage of mature 16S rRNA. Here, using paired-end RNA sequencing (RNA-seq) and ribosome profiling, we provide a comprehensive, global analysis of MazF cleavage specificity and its targets...
May 17, 2018: Molecular Cell
Bartosz Roszniowski, Siobhán McClean, Zuzanna Drulis-Kawa
Burkholderia cenocepacia , is a Gram-negative opportunistic pathogen that belongs to Burkholderia cepacia complex (BCC) group. BCC representatives carry various pathogenicity factors and can infect humans and plants. Phages as bacterial viruses play a significant role in biodiversity and ecological balance in the environment. Specifically, horizontal gene transfer (HGT) and lysogenic conversion (temperate phages) influence microbial diversification and fitness. In this study, we describe the prevalence and gene content of prophages in 16 fully sequenced B...
May 31, 2018: Viruses
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
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