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Journal articles on the topic 'MazEF TA system'

Author: Grafiati

Published: 6 September 2023

Last updated: 31 July 2025

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1

Jin, Chenglong, Sung-Min Kang, Do-Hee Kim, and Bong-Jin Lee. "Structural and functional analysis of the Klebsiella pneumoniae MazEF toxin–antitoxin system." IUCrJ 8, no. 3 (2021): 362–71. http://dx.doi.org/10.1107/s2052252521000452.

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Bacterial toxin–antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of Klebsiella pneumoniae at 2.3 Å resolution is presented. The K. pneumoniae MazEF complex consists of two MazEs and four MazFs in a heterohexameric assembly. It was estimated that MazEF forms a dodecamer with two heterohexameric MazEF complexes in solution, and a truncated complex exists in heterohexameric form. The MazE antitoxin interacts with the MazF toxin via two binding modes

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2

Jin, Chenglong, Sung-Min Kang, Do-Hee Kim, Yuno Lee, and Bong-Jin Lee. "Discovery of Antimicrobial Agents Based on Structural and Functional Study of the Klebsiella pneumoniae MazEF Toxin–Antitoxin System." Antibiotics 13, no. 5 (2024): 398. http://dx.doi.org/10.3390/antibiotics13050398.

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Klebsiella pneumoniae causes severe human diseases, but its resistance to current antibiotics is increasing. Therefore, new antibiotics to eradicate K. pneumoniae are urgently needed. Bacterial toxin–antitoxin (TA) systems are strongly correlated with physiological processes in pathogenic bacteria, such as growth arrest, survival, and apoptosis. By using structural information, we could design the peptides and small-molecule compounds that can disrupt the binding between K. pneumoniae MazE and MazF, which release free MazF toxin. Because the MazEF system is closely implicated in programmed cel

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3

Tang, Ziyun, Pengcheng Jiang та Wei Xie. "Long Dynamic β1–β2 Loops in M. tb MazF Toxins Affect the Interaction Modes and Strengths of the Toxin–Antitoxin Pairs". International Journal of Molecular Sciences 25, № 17 (2024): 9630. http://dx.doi.org/10.3390/ijms25179630.

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Tuberculosis is a worldwide plague caused by the pathogen Mycobacterium tuberculosis (M. tb). Toxin–antitoxin (TA) systems are genetic elements abundantly present in prokaryotic organisms and regulate important cellular processes. MazEF is a TA system implicated in the formation of “persisters cells” of M. tb, which contain more than 10 such members. However, the exact function and inhibition mode of each MazF are not fully understood. Here we report crystal structures of MazF-mt3 in its apo form and in complex with the C-terminal half of MazE-mt3. Structural analysis suggested that two long b

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4

Nigam, Akanksha, Adi Oron-Gottesman, and Hanna Engelberg-Kulka. "A Bias in the Reading of the Genetic Code of Escherichia coli is a Characteristic for Genes that Specify Stress-induced MazF-mediated Proteins." Current Genomics 21, no. 4 (2020): 311–18. http://dx.doi.org/10.2174/1389202921999200606215305.

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Background: Escherichia coli (E. coli) mazEF, a stress-induced toxin-antitoxin (TA) system, has been studied extensively. The MazF toxin is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a Stress-induced Translation Machinery (STM), composed of MazF processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Materials and Methods: Escherichia coli (E. coli) mazEF, a stress-induced toxin-antitoxin (TA) system, has been studied extensively. The MazF toxin is an endoribonuclease that cleaves RNAs at ACA sites. The

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5

Choi, Wonho, Yoshihiro Yamaguchi, Ji-Young Park, et al. "Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens." Microorganisms 9, no. 5 (2021): 1107. http://dx.doi.org/10.3390/microorganisms9051107.

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Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The

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Norouzi, Masoumeh, Abbas Maleki, Elham Aboualigalehdari, and Sobhan Ghafourian. "Type II toxin- antitoxin systems in clinical isolates of antibiotic resistant Acinetobacter baumannii." Genetika 54, no. 2 (2022): 625–32. http://dx.doi.org/10.2298/gensr2202625n.

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The over use of antibiotics to treat infections in humans and animals made a phenomenon of the antibiotic-resistant bacteria. While studies focused to find on new antibiotics but, identification of novel antibacterial targets in bacteria is very important. By Toxin antitoxin systems this hypothesis could be done, whereas by the activation of a toxin or inactivation of an antitoxin, the raised toxin kills the bacterium. These systems are attractive target for antimicrobial therapy. However, the most important step for potency of TA system, as an antibacterial target, is to identify a TA system

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7

Tsilibaris, Virginie, Geneviève Maenhaut-Michel, Natacha Mine, and Laurence Van Melderen. "What Is the Benefit to Escherichia coli of Having Multiple Toxin-Antitoxin Systems in Its Genome?" Journal of Bacteriology 189, no. 17 (2007): 6101–8. http://dx.doi.org/10.1128/jb.00527-07.

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ABSTRACT The Escherichia coli K-12 chromosome encodes at least five proteic toxin-antitoxin (TA) systems. The mazEF and relBE systems have been extensively characterized and were proposed to be general stress response modules. On one hand, mazEF was proposed to act as a programmed cell death system that is triggered by a variety of stresses. On the other hand, relBE and mazEF were proposed to serve as growth modulators that induce a dormancy state during amino acid starvation. These conflicting hypotheses led us to test a possible synergetic effect of the five characterized E. coli TA systems

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8

Hosseini, Mandana, Jamileh Nowroozi, and Nour Amirmozafari. "The effect of type II toxin-antitoxin systems on methicillinresistant Staphylococcus aureus persister cell formation and antibiotic tolerance." Acta Biologica Szegediensis 65, no. 1 (2021): 113–17. http://dx.doi.org/10.14232/abs.2021.1.113-117.

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Persister cells are defi ned as a subpopulation of bacteria in a dormant state with the ability to reduce bacterial metabolism and they are involved in antibiotic tolerance. Toxin-antitoxin (TA) systems have been previously suggested as important players in persistence. Therefore, this study aimed to study the involvement of TA systems in persister cell formation in methicillin-resistant Staphylococcus aureus following antibiotic exposure. Using TADB and RASTA database, two type II TA systems including MazF/MazE and RelE/RelB were predicted in S. aureus. The presence of these TA genes was dete

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Alkhalili, Rawana, Joel Wallenius, and Björn Canbäck. "Towards Exploring Toxin-Antitoxin Systems in Geobacillus: A Screen for Type II Toxin-Antitoxin System Families in a Thermophilic Genus." International Journal of Molecular Sciences 20, no. 23 (2019): 5869. http://dx.doi.org/10.3390/ijms20235869.

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The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating stress responses in prokaryotes and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, while thermophiles have received merely limited attention. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using protein domain analysis tools. We also used the NCBI BLAST, Operon Mapper, ProOpDB, and sequence ali

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10

Valizadeh, Nasrin, Firuzeh Valian, Nourkhoda Sadeghifard, et al. "The Role of Peganum harmala Ethanolic Extract and Type II Toxin Antitoxin System in Biofilm Formation." Drug Research 67, no. 07 (2017): 385–87. http://dx.doi.org/10.1055/s-0043-102060.

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AbstractToxin 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. Our results demonstrated that relBE TA loci were dominant TA loci; whe

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11

Chen, Ran, Jie Tu, Yaoju Tan, et al. "Structural and Biochemical Characterization of the Cognate and Heterologous Interactions of the MazEF-mt9 TA System." ACS Infectious Diseases 5, no. 8 (2019): 1306–16. http://dx.doi.org/10.1021/acsinfecdis.9b00001.

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12

Chen, Ran, Jie Tu, Yaoju Tan, et al. "Correction to Structural and Biochemical Characterization of the Cognate and Heterologous Interactions of the MazEF-mt9 TA System." ACS Infectious Diseases 6, no. 9 (2020): 2543. http://dx.doi.org/10.1021/acsinfecdis.0c00577.

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13

Shapira, Shiran, Ilana Boustanai, Dina Kazanov, Marina Ben Shimon, Ahmad Fokra, and Nadir Arber. "Innovative dual system approach for selective eradication of cancer cells using viral-based delivery of natural bacterial toxin–antitoxin system." Oncogene 40, no. 31 (2021): 4967–79. http://dx.doi.org/10.1038/s41388-021-01792-8.

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AbstractThe inactivation of p53, a tumor suppressor, and the activation of the RAS oncogene are the most frequent genetic alterations in cancer. We have shown that a unique E. coli MazF-MazE toxin–antitoxin (TA) system can be used for selective and effective eradication of RAS-mutated cancer cells. This out of the box strategy holds great promise for effective cancer treatment and management. We provide proof of concept for a novel platform to selectively eradicate cancer cells using an adenoviral delivery system based on the adjusted natural bacterial system. We generated adenoviral vectors c

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14

Shapira, Shiran, Ilana Boustanai, Dina Kazanov, et al. "Innovative dual system for selective eradication of cancer cells using exosomes carrying natural bacterial toxin-antitoxin (TA)." Journal of Clinical Oncology 37, no. 15_suppl (2019): e14635-e14635. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14635.

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e14635 Background: Inactivation of P53 and activation of ras are frequent genetic alterations in cancer. We have shown in vitro and in vivo, that the TA system can selectively and effectively eradicate RAS-mutated cancer cells. Aim: Selective killing of cancer cells while sparing the normal cells based on tumor genetic signature. Methods: A “first generation” ΔE1/ΔE3 human type-5 adenoviral-vectors for gene delivery were designed and constructed to specifically target cancer cells. They are designated as "PY4-mazF-mCherry" (PY4, ras responsive element), "ΔPY4-mazF-mCherry" (control viruses) an

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15

Donegan, Niles P., Earl T. Thompson, Zhibiao Fu, and Ambrose L. Cheung. "Proteolytic Regulation of Toxin-Antitoxin Systems by ClpPC in Staphylococcus aureus." Journal of Bacteriology 192, no. 5 (2009): 1416–22. http://dx.doi.org/10.1128/jb.00233-09.

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ABSTRACT Bacterial toxin-antitoxin (TA) systems typically consist of a small, labile antitoxin that inactivates a specific longer-lived toxin. In Escherichia coli, such antitoxins are proteolytically regulated by the ATP-dependent proteases Lon and ClpP. Under normal conditions, antitoxin synthesis is sufficient to replace this loss from proteolysis, and the bacterium remains protected from the toxin. However, if TA production is interrupted, antitoxin levels decrease, and the cognate toxin is free to inhibit the specific cellular component, such as mRNA, DnaB, or gyrase. To date, antitoxin de

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16

Kim, Younghoon, Xiaoxue Wang, Qun Ma, Xue-Song Zhang, and Thomas K. Wood. "Toxin-Antitoxin Systems in Escherichia coli Influence Biofilm Formation through YjgK (TabA) and Fimbriae." Journal of Bacteriology 191, no. 4 (2008): 1258–67. http://dx.doi.org/10.1128/jb.01465-08.

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ABSTRACT The roles of toxin-antitoxin (TA) systems in bacteria have been debated. Here, the role of five TA systems in regard to biofilm development was investigated (listed as toxin/antitoxin: MazF/MazE, RelE/RelB, ChpB, YoeB/YefM, and YafQ/DinJ). Although these multiple TA systems were reported previously to not impact bacterial fitness, we found that deletion of the five TA systems decreased biofilm formation initially (8 h) on three different surfaces and then increased biofilm formation (24 h) by decreasing biofilm dispersal. Whole-transcriptome profiling revealed that the deletion of the

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17

SINGH, RANDHIR, and XIUPING JIANG. "Expression of Stress and Virulence Genes in Escherichia coli O157:H7 Heat Shocked in Fresh Dairy Compost." Journal of Food Protection 78, no. 1 (2015): 31–41. http://dx.doi.org/10.4315/0362-028x.jfp-13-529.

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The purpose of this study was to determine the gene expression of Escherichia coli O157:H7 heat shocked in dairy compost. A two-step real-time PCR assay was used to evaluate the expression of stress and virulence genes in E. coli O157:H7 heat shocked in compost at 47.5°C for 10 min. Heat-shocked E. coli O157:H7 in compost was isolated by using an immunomagnetic bead separation method, followed by total RNA extraction, which was then converted to cDNA by using a commercial kit. E. coli O157:H7 heat shocked in broth served as the media control. In compost, heat shock genes (clpB, dnaK, and groEL

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18

Rodamilans, Bernardo, Xiaofei Cheng, Carmen Simón-Mateo, and Juan Antonio García. "Use of Bacterial Toxin–Antitoxin Systems as Biotechnological Tools in Plants." International Journal of Molecular Sciences 25, no. 19 (2024): 10449. http://dx.doi.org/10.3390/ijms251910449.

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Toxin–antitoxin (TA) systems in bacteria are key regulators of the cell cycle and can activate a death response under stress conditions. Like other bacterial elements, TA modules have been widely exploited for biotechnological purposes in diverse applications, such as molecular cloning and anti-cancer therapies. However, their use in plants has been limited, leaving room for the development of new approaches. In this study, we examined two TA systems previously tested in plants, MazEF and YefM-YoeB, and identified interesting differences between them, likely related to their modes of action. W

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Kang, Sung-Min, Ji Sung Koo, Chang-Min Kim, Do-Hee Kim, and Bong-Jin Lee. "mRNA Interferase Bacillus cereus BC0266 Shows MazF-Like Characteristics Through Structural and Functional Study." Toxins 12, no. 6 (2020): 380. http://dx.doi.org/10.3390/toxins12060380.

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Toxin–antitoxin (TA) systems are prevalent in bacteria and are known to regulate cellular growth in response to stress. As various functions related to TA systems have been revealed, the importance of TA systems are rapidly emerging. Here, we present the crystal structure of putative mRNA interferase BC0266 and report it as a type II toxin MazF. The MazF toxin is a ribonuclease activated upon and during stressful conditions, in which it cleaves mRNA in a sequence-specific, ribosome-independent manner. Its prolonged activity causes toxic consequences to the bacteria which, in turn, may lead to

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Ewalds-Kvist, S. Béatrice M., Ritva-Kajsa Selander, and N. Kenneth Sandnabba. "Sex-Related Coping Responses in Mice Selectively Bred for Aggression." Perceptual and Motor Skills 84, no. 3 (1997): 911–14. http://dx.doi.org/10.2466/pms.1997.84.3.911.

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Sex differences in strategies of coping with novel situations were studied in three strains of mice with regard to metabolism and open-field and maze activity as well as learning-induced adjustment. The 140 mice were selectively bred for high (Turku Aggressive [TA]) and low (Turku Nonaggressive [TNA]) levels of aggressiveness and originated from a Swiss albino stock normally distributed [N] for aggressiveness. The results indicated that TNA sex differences are more similar to those of the control N mice as compared to those of TA mice. In maze learning, however, the sex differences of TA mice

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Tandon, Himani, Akhila Melarkode Vattekatte, Narayanaswamy Srinivasan, and Sankaran Sandhya. "Molecular and Structural Basis of Cross-Reactivity in M. tuberculosis Toxin–Antitoxin Systems." Toxins 12, no. 8 (2020): 481. http://dx.doi.org/10.3390/toxins12080481.

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Mycobacterium tuberculosis genome encodes over 80 toxin–antitoxin (TA) systems. While each toxin interacts with its cognate antitoxin, the abundance of TA systems presents an opportunity for potential non-cognate interactions. TA systems mediate manifold interactions to manage pathogenicity and stress response network of the cell and non-cognate interactions may play vital roles as well. To address if non-cognate and heterologous interactions are feasible and to understand the structural basis of their interactions, we have performed comprehensive computational analyses on the available 3D str

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Selander, Ritva-Kajsa, and S. Béatrice M. Kvist. "Open-Field Parameters and Maze Learning in Aggressive and Nonaggressive Male Mice." Perceptual and Motor Skills 73, no. 3 (1991): 811–24. http://dx.doi.org/10.2466/pms.1991.73.3.811.

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Significant differences were observed in thigmotaxis, ambulation, and latency to move (time to start ambulating) between highly aggressive (TA) and low aggressive (TNA) male mice. The former displayed more thigmotaxis, ambulated more, and had a shorter latency to move than the TNA animals. Also they voided a greater number of urinary spots and defecated less than TNA. Further they were superior to the TNA mice in maze-learning capacity. The tendency to enter inner partitions of the field as well as total ambulation increased after learning by TA mice. The training toward nonaggressiveness of T

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Wang, Xiaoxue, and Thomas K. Wood. "Toxin-Antitoxin Systems Influence Biofilm and Persister Cell Formation and the General Stress Response." Applied and Environmental Microbiology 77, no. 16 (2011): 5577–83. http://dx.doi.org/10.1128/aem.05068-11.

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ABSTRACTIn many genomes, toxin-antitoxin (TA) systems have been identified; however, their role in cell physiology has been unclear. Here we examine the evidence that TA systems are involved in biofilm formation and persister cell formation and that these systems may be important regulators of the switch from the planktonic to the biofilm lifestyle as a stress response by their control of secondary messenger 3′,5′-cyclic diguanylic acid. Specifically, upon stress, the sequence-specific mRNA interferases MqsR and MazF mediate cell survival. In addition, we propose that TA systems are not redund

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Shapira, Shiran, Daniela Eisurovich, Dina Kazanov, and Nadir Arber. "Abstract 1707: Establishment of a targeted exosome drug delivery system containing natural bacterial toxins and antitoxins." Cancer Research 83, no. 7_Supplement (2023): 1707. http://dx.doi.org/10.1158/1538-7445.am2023-1707.

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Abstract Background: The inactivation of p53, a tumor suppressor, and the activation of the Ras oncogene are the most frequent genetic alterations in cancer. We have shown that a unique E. coli MazF-MazE toxin-antitoxin (TA) system, controlled by Ras and p53, delivered via adenoviruses can be used to selectively and effectively eradicate Ras mutated cancer cells (Shapira et al., oncogene, 2021). Because of their low immunogenicity and known advantage as ideal cell transporters, exosomes offer great promise as cancer immunotherapy agents. CD24 is a GPI-anchored protein that highly expressed in

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Maleki, Abbas, Sobhan Ghafourian, Iraj Pakzad, Behzad Badakhsh, and Nourkhoda Sadeghifard. "mazE Antitoxin of Toxin Antitoxin System and fbpA as Reliable Targets to Eradication of Neisseria meningitidis." Current Pharmaceutical Design 24, no. 11 (2018): 1204–10. http://dx.doi.org/10.2174/1381612824666171213094730.

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Background: Neisseria meningitidis is considered as a dangerous pathogen threatening human health. Nowadays, the new drug target is focused. Toxin antitoxin (TA) system is recently identified as an antimicrobial drug target. Also, in N. meningitidis, iron-uptake system could be an interesting target for drug discovery. Methods: In this study, fbpA and mazE genes were chosen as new antimicrobial targets and treated with antisense peptide nucleic acid (PNA). Firstly, they were evaluated by bioinformatics and then analyzed by experimental procedures. Secondly, the functionality was evaluated by s

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Tasneem, Maisha, Shipan Das Gupta, Monira Binte Momin, Kazi Modasser Hossain, Tasnim Binta Osman, and Md Fazley Rabbi. "In silico annotation of a hypothetical protein from Listeria monocytogenes EGD-e unfolds a toxin protein of the type II secretion system." Genomics & Informatics 21, no. 1 (2023): e7. http://dx.doi.org/10.5808/gi.22071.

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The gram-positive bacterium Listeria monocytogenes is an important foodborne intracellular pathogen that is widespread in the environment. The functions of hypothetical proteins (HP) from various pathogenic bacteria have been successfully annotated using a variety of bioinformatics strategies. In this study, a HP Imo0888 (NP_464414.1) from the Listeria monocytogenes EGD-e strain was annotated using several bioinformatics tools. Various techniques, including CELLO, PSORTb, and SOSUIGramN, identified the candidate protein as cytoplasmic. Domain and motif analysis revealed that the target protein

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Shafipour, Maryam, Abdolmajid Mohammadzadeh, Pezhman Mahmoodi, Mahdi Dehghanpour, and Ezzat Allah Ghaemi. "Distribution of lineages and type II toxin-antitoxin systems among rifampin-resistant Mycobacterium Tuberculosis Isolates." PLOS ONE 19, no. 10 (2024): e0309292. http://dx.doi.org/10.1371/journal.pone.0309292.

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Type II toxin-antitoxin systems such as mazEF3, vapBC3, and relJK play a role in antibiotic resistance and tolerance. Among the different known TA systems, mazEF3, vapBC3, and relJK, which are type II systems, have specific roles in drug resistance. Therefore, the aim of this study was to investigate the mutations in these genes in sensitive and resistant isolates of Mycobacterium tuberculosis. Thirty-two rifampin-resistant and 121 rifampin-sensitive M. tuberculosis isolates were collected from various regions of Iran. Lineage typing was performed using the ASO-PCR method. Mutations in the rpo

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Jørgensen, Mikkel G., Deo P. Pandey, Milena Jaskolska, and Kenn Gerdes. "HicA of Escherichia coli Defines a Novel Family of Translation-Independent mRNA Interferases in Bacteria and Archaea." Journal of Bacteriology 191, no. 4 (2008): 1191–99. http://dx.doi.org/10.1128/jb.01013-08.

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ABSTRACT Toxin-antitoxin (TA) loci are common in free-living bacteria and archaea. TA loci encode a stable toxin that is neutralized by a metabolically unstable antitoxin. The antitoxin can be either a protein or an antisense RNA. So far, six different TA gene families, in which the antitoxins are proteins, have been identified. Recently, Makarova et al. (K. S. Makarova, N. V. Grishin, and E. V. Koonin, Bioinformatics 22:2581-2584, 2006) suggested that the hicAB loci constitute a novel TA gene family. Using the hicAB locus of Escherichia coli K-12 as a model system, we present evidence that su

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Chandra, Soumyanetra, Gopinath Chattopadhyay, and Raghavan Varadarajan. "Rapid Identification of Secondary Structure and Binding Site Residues in an Intrinsically Disordered Protein Segment." Frontiers in Genetics 12 (November 2, 2021). http://dx.doi.org/10.3389/fgene.2021.755292.

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Mycobacterium tuberculosis harbours nine toxin-antitoxin (TA) systems of the MazEF family. MazEF TA modules are of immense importance due to the perceived role of the MazF toxin in M. tuberculosis persistence and disease. The MazE antitoxin has a disordered C-terminal domain that binds the toxin, MazF and neutralizes its endoribonuclease activity. However, the structure of most MazEF TA complexes remains unsolved till date, obscuring structural and functional information about the antitoxins. We present a facile method to identify toxin binding residues on the disordered antitoxin. Charged res

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Nim, Jogendra Singh, Mohit Yadav, Lalit Kumar Gautam, Chaitali Ghosh, Shakti Sahi, and Jitendra Singh Rathore. "Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophi-la: Identification, Characterization and Functional Exploration." Current Computer-Aided Drug Design 16 (June 25, 2020). http://dx.doi.org/10.2174/1573409916666200625135850.

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Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3 D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin

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Dai, Jingli, Zijing Chen, Jinfeng Hou, et al. "MazEF Toxin-Antitoxin System-Mediated DNA Damage Stress Response in Deinococcus radiodurans." Frontiers in Genetics 12 (February 19, 2021). http://dx.doi.org/10.3389/fgene.2021.632423.

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Deinococcus radiodurans shows marked resistance to various types of DNA-damaging agents, including mitomycin C (MMC). A type II toxin-antitoxin (TA) system that responds to DNA damage stress was identified in D. radiodurans, comprising the toxin MazF-dr and the antitoxin MazE-dr. The cleavage specificity of MazF-dr, an endoribonuclease, was previously characterized. Here, we further investigated the regulatory role of the MazEF system in the response to DNA damage stress in D. radiodurans. The crystal structure of D. radiodurans MazF (MazF-dr) was determined at a resolution of 1.3 Å and is the

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Sultan, Amira M., and Nawal S. Gouda. "The Association of the mazEF Toxin-antitoxin System and Vancomycin Resistance in Clinical Isolates of Vancomycin Resistant Enterococcus faecalis." Journal of Pure and Applied Microbiology, May 31, 2022. http://dx.doi.org/10.22207/jpam.16.2.46.

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Vancomycin resistant enterococci are challenging bacteria as they are difficult to be eradicated. Toxin-antitoxin (TA) systems are genetic elements located in most prokaryotic genomes. The mazEF TA system is harbored by a plasmid among Enterococcus faecalis (E. faecalis). To explore the relation between the existence of mazEF TA system and vancomycin resistance among clinical isolates of E. faecalis. Samples were collected from patients showing clinical picture of infection. Isolates of E. faecalis were identified by standard microbiological methods and their antimicrobial susceptibility patte

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Kumari, Khushboo, and Siddhartha P. Sarma. "Structural and mutational analysis of MazE6-operator DNA complex provide insights into autoregulation of toxin-antitoxin systems." Communications Biology 5, no. 1 (2022). http://dx.doi.org/10.1038/s42003-022-03933-5.

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AbstractOf the 10 paralogs of MazEF Toxin-Antitoxin system in Mycobacterium tuberculosis, MazEF6 plays an important role in multidrug tolerance, virulence, stress adaptation and Non Replicative Persistant (NRP) state establishment. The solution structures of the DNA binding domain of MazE6 and of its complex with the cognate operator DNA show that transcriptional regulation occurs by binding of MazE6 to an 18 bp operator sequence bearing the TANNNT motif (-10 region). Kinetics and thermodynamics of association, as determined by NMR and ITC, indicate that the nMazE6-DNA complex is of high affin

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Al-Hadban, Wedean, Maysaa Adil Ali, and Nuha Kandala. "The Correlation Between the Persistence of Methicillin Resistant Staphylococcus Aureus Isolates to Mupirocine and Toxin-Antitoxin Type II Genes." Iraqi Journal of Science, May 25, 2022, 1930–40. http://dx.doi.org/10.24996/ijs.2022.63.5.7.

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Under high concentrations of antibiotics, a fraction of the bacterial population exhibits a phenomenon known as persistence. Toxin- system (TA system) has been reported to be involved in the formation of E. coli, Mycobacterium, and S. aureus persisters. In this study, the ability of thirty Iraqi isolates of MRSA to form in vitro persister cells after exposure to three different antibiotics (Ceftriaxone 30 µg, Mecillinam 10 µg, and Mupirocin 20 µg) was examined by TD test. Additionally, efflux pump inhibitor [Fluphenazine 0.25 mg/ml] was combined with the antibiotic that triggered persister for

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Wei, Yanxia, Yang Li, Fan Yang, et al. "Physical and Functional Interplay between MazF1Bif and Its Noncognate Antitoxins from Bifidobacterium longum." Applied and Environmental Microbiology 83, no. 9 (2017). http://dx.doi.org/10.1128/aem.03232-16.

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ABSTRACT Bifidobacterium longum strain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) system in its chromosome, designated MazE1F1 Bif, MazE2F2 Bif, and RelBEBif, respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interactions between MazF1 Bif and MazE2 Bif or RelBBif were assessed in B. longum strain JDM301. MazF1 Bif caused the degradation of tufA Bif mRNA, and its toxicity was inhibited by

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Jain, Sonia, Arghya Bhowmick, Bohyun Jeong, Taeok Bae, and Abhrajyoti Ghosh. "Unravelling the physiological roles of mazEF toxin–antitoxin system on clinical MRSA strain by CRISPR RNA-guided cytidine deaminase." Journal of Biomedical Science 29, no. 1 (2022). http://dx.doi.org/10.1186/s12929-022-00810-5.

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Abstract Background Curiosity on toxin–antitoxin modules has increased intensely over recent years as it is ubiquitously present in many bacterial genomes, including pathogens like Methicillin-resistant Staphylococcus aureus (MRSA). Several cellular functions of TA systems have been proposed however, their exact role in cellular physiology remains unresolved. Methods This study aims to find out the impact of the mazEF toxin–antitoxin module on biofilm formation, pathogenesis, and antibiotic resistance in an isolated clinical ST239 MRSA strain, by constructing mazE and mazF mutants using CRISPR

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Alexander, Cyrus, Ankeeta Guru, Pinkilata Pradhan, et al. "MazEF-rifampicin interaction suggests a mechanism for rifampicin induced inhibition of persisters." BMC Molecular and Cell Biology 21, no. 1 (2020). http://dx.doi.org/10.1186/s12860-020-00316-8.

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Abstract Background Persistence is a natural phenomenon whereby a subset of a population of isogenic bacteria either grow slow or become dormant conferring them with the ability to withstand various stresses including antibiotics. In a clinical setting bacterial persistence often leads to the recalcitrance of various infections increasing the treatment time and cost. Additionally, some studies also indicate that persistence can also pave way for the emergence of resistant strains. In a laboratory setting this persistent phenotype is enriched in nutritionally deprived environments. Consequently

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Valadbeigi, Hassan, Nourkhoda Sadeghifard, Vahab Hassan Kaviar, Mohammad Hossein Haddadi, Sobhan Ghafourian, and Abbas Maleki. "Effect of ZnO nanoparticles on biofilm formation and gene expression of the toxin-antitoxin system in clinical isolates of Pseudomonas aeruginosa." Annals of Clinical Microbiology and Antimicrobials 22, no. 1 (2023). http://dx.doi.org/10.1186/s12941-023-00639-2.

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Abstract Background Biofilm formation by Pseudomonas aeruginosa (P. aeruginosa) is known to be characteristic of this organism. This bacterium is considered one of the most life-threatening bacteria and has been identified as a priority pathogen for research by WHO. Biofilm-producing P. aeruginosa is a concern in many parts of the world due to antibiotic resistance. Alginate also plays an important role in the biofilm formation of P. aeruginosa as well as the emergence of antibiotic resistance in biofilms. In addition, the systems of toxin-antitoxin( TA) play an important role in biofilm forma

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Oron-Gottesman, Adi, Martina Sauert, Isabella Moll, and Hanna Engelberg-Kulka. "A Stress-Induced Bias in the Reading of the Genetic Code in Escherichia coli." mBio 7, no. 6 (2016). http://dx.doi.org/10.1128/mbio.01855-16.

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ABSTRACT Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a stress-induced translation machinery (STM), composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we further characterized the STM system, finding that MazF cleaves only ACA sites located in the open reading frames of processed mRNAs, while out-of-frame ACAs are resistant. This in-frame ACA cleavage of MazF seems to

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Nigam, Akanksha, Tamar Ziv, Adi Oron-Gottesman, and Hanna Engelberg-Kulka. "Stress-Induced MazF-Mediated Proteins in Escherichia coli." mBio 10, no. 2 (2019). http://dx.doi.org/10.1128/mbio.00340-19.

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ABSTRACT Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. By that means, under stress, the induced MazF generates a stress-induced translation machinery (STM) composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we performed a proteomic analysis of all the E. coli stress-induced proteins that are mediated through the chromosomally borne mazF gene. We show that the mRNAs of almost all of them are characterized by the presenc

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Sundaram, Karthikeyan, Leela Kagithakara Vajravelu, Ravichandiran Velayutham, and Utpal Mohan. "Identification of Genes Encoded Toxin-Antitoxin System in Mycobacterium Tuberculosis Strains from Clinical Sample." Infectious Disorders - Drug Targets 24 (March 14, 2024). http://dx.doi.org/10.2174/0118715265274164240117104534.

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Background:: The toxin-antitoxin system is a genetic element that is highly present in Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. The toxin-antitoxin sys-tem comprises toxin protein and antitoxin protein or non-encoded RNA interacting with each other and inhibiting toxin activity. M. Tuberculosis has more classes of TA loci than non-tubercle bacilli and other microbes, including VapBC, HigBA, MazEF, ParDE, RelBE, MbcTA, PemIK, DarTG, MenTA, one tripartite type II TAC chaperone system, and hypothetical proteins. Aims:: The study aims to demonstrate the genes encoded

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Tian, Xiao-Lin, Miao Li, Zachariah Scinocca, Heather Rutherford, and Yung-Hua Li. "ClpP is required for proteolytic regulation of type II toxin–antitoxin systems and persister cell formation in Streptococcus mutans." Access Microbiology 1, no. 8 (2019). http://dx.doi.org/10.1099/acmi.0.000054.

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The type II toxin–antitoxin (TA) modules, mazEF and relBE, in Streptococcus mutans have been implicated in stress response, antibiotic tolerance and persister cell formation. However, how S. mutans regulates these systems to prevent unwanted toxin activation and persister cell formation is unclear. In this study, we provide evidence that ClpP is required for the proteolytic regulation of these TA systems and persister cell formation in S. mutans following antibiotic challenge. A persister viability assay showed that S. mutans UA159 (WT) formed a larger quantity of persister cells than its isog

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Tamiya-Ishitsuka, Hiroko, Masako Tsuruga, Naohiro Noda, and Akiko Yokota. "Conserved Amino Acid Moieties of Candidatus Desulforudis audaxviator MazF Determine Ribonuclease Activity and Specificity." Frontiers in Microbiology 12 (November 11, 2021). http://dx.doi.org/10.3389/fmicb.2021.748619.

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The toxin-antitoxin (TA) system, inherent to various prokaryotes, plays a critical role in survival and adaptation to diverse environmental stresses. The toxin MazF, belonging to the type II TA system, functions as a sequence-specific ribonuclease that recognizes 3 to 7 bases. In recent studies, crystallographic analysis of MazFs from several species have suggested the presence of amino acid sites important for MazF substrate RNA binding and for its catalytic activity. Herein, we characterized MazF obtained from Candidatus Desulforudis audaxviator (MazF-Da) and identified the amino acid residu

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Chattopadhyay, Gopinath, Munmun Bhasin, Shahbaz Ahmed, et al. "Functional and Biochemical Characterization of the MazEF6 Toxin-Antitoxin System of Mycobacterium tuberculosis." Journal of Bacteriology 204, no. 4 (2022). http://dx.doi.org/10.1128/jb.00058-22.

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M. tuberculosis harbors a large number of type II toxin-antitoxin (TA) systems, the exact roles for most of which are unclear. Prior studies have reported that overexpression of several of these type II toxins inhibits bacterial growth and contributes to the formation of drug-tolerant populations in vitro .

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Fico, Sarah, and Jacques Mahillon. "TasA-tasB, a new putative toxin-antitoxin (TA) system from Bacillus thuringiensis pGI1 plasmid is a widely distributed composite mazE-doc TA system." BMC Genomics 7, no. 1 (2006). http://dx.doi.org/10.1186/1471-2164-7-259.

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Kheradmand, Erfan, Shabnam Razavi, Malihe Talebi, and Mahmood Jamshidian. "Evaluation of Putative Type II Toxin-Antitoxin Systems and Lon Protease Expression in Shigella flexneri Following Infection of Caco-2 Cells." Archives of Clinical Infectious Diseases 15, no. 3 (2020). http://dx.doi.org/10.5812/archcid.98625.

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: Shigella flexneri causes bacillary dysentery in developing countries. Due to recent reports regarding antimicrobial resistance in human S. flexneri, finding alternative therapeutics is of vital importance. Toxin-antitoxin (TA) systems have recently been introduced as antimicrobial targets owing to their involvement in bacterial survival in stress conditions and “persister” cell formation. In this study, the presence of four TA loci were studied in S. flexneri ATCC 12022. The presence of genes coding for the identified TA loci and Lon protease were confirmed by the PCR method using specific p

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Karimaei, Samira, Behrooz Sadeghi Kalani, Nader Shahrokhi, Rahil Mashhadi, and Mohammad Reza Pourmand. "Expression of type II toxin-antitoxin systems and ClpP protease of methicillin-resistant Staphylococcus aureus under thermal and oxidative stress conditions." Iranian Journal of Microbiology, April 14, 2021. http://dx.doi.org/10.18502/ijm.v13i2.5982.

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Background and Objectives: Staphylococcus aureus is a main human pathogen that causes a variety of chronic to persistent infections. Across the diverse factors of pathogenesis in bacteria, Toxin-Antitoxin (TA) systems can be considered as an antibacterial target due to their involvement in cellular physiology counting stress responses. Here, the expression of TA system genes and ClpP protease was investigated under the thermal and oxidative conditions in S. aureus strains. Materials and Methods: The colony-forming unit (CFU) was used to determine the effects of thermal and oxidative stre

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Ardissone, Silvia, and Gilbert Greub. "The Chlamydia -related Waddlia chondrophila encodes functional type II toxin-antitoxin systems." Applied and Environmental Microbiology, January 12, 2024. http://dx.doi.org/10.1128/aem.00681-23.

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ABSTRACT Bacterial toxin-antitoxin (TA) systems are widespread in chromosomes and plasmids of free-living microorganisms, but only a few have been identified in obligate intracellular species. We found seven putative type II TA modules in Waddlia chondrophila , a Chlamydia -related species that is able to infect a very broad series of eukaryotic hosts, ranging from protists to mammalian cells. The RNA levels of Waddlia TA systems are significantly upregulated by iron starvation and novobiocin, but they are not affected by antibiotics such as β-lactams and glycopeptides, which suggests differen

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Hou, Yawei, Yifan Li, Ningning Tao, et al. "Toxin-antitoxin system gene mutations driving Mycobacterium tuberculosis transmission revealed by whole genome sequencing." Frontiers in Microbiology 15 (July 31, 2024). http://dx.doi.org/10.3389/fmicb.2024.1398886.

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BackgroundThe toxin-antitoxin (TA) system plays a vital role in the virulence and pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). However, the regulatory mechanisms and the impact of gene mutations on M. tuberculosis transmission remain poorly understood.ObjectiveTo investigate the influence of gene mutations in the toxin-antitoxin system on M. tuberculosis transmission dynamics.MethodWe performed whole-genome sequencing on the analyzed strains of M. tuberculosis. The genes associated with the toxin-antitoxin system were obtained from the National Center for Biotechnology Inform

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Garcia, Pamela K., Rosemarie Martinez Borrero, Thirunavukkarasu Annamalai, et al. "Localization of Mycobacterium tuberculosis topoisomerase I C-terminal sequence motif required for inhibition by endogenous toxin MazF4." Frontiers in Microbiology 13 (December 5, 2022). http://dx.doi.org/10.3389/fmicb.2022.1032320.

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Only about half the multi-drug resistant tuberculosis (MDR-TB) cases are successfully cured. Thus, there is an urgent need of new TB treatment against a novel target. Mycobacterium tuberculosis (Mtb) topoisomerase I (TopA) is the only type IA topoisomerase in this organism and has been validated as an essential target for TB drug discovery. Toxin-antitoxin (TA) systems participate as gene regulators within bacteria. The TA systems contribute to the long-term dormancy of Mtb within the host-cell environment. Mtb’s toxin MazF4 (Rv1495) that is part of the MazEF4 TA system has been shown to have

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