Review
Biochemistry & Molecular Biology
Pieter De Bruyn, Yana Girardin, Remy Loris
Summary: Toxin-antitoxin (TA) modules are small operons in bacteria and archaea that encode a metabolic inhibitor (toxin) and a matching regulatory protein (antitoxin). Although their biochemical activities are well defined, their biological functions remain unclear. The different TA modules vary significantly regarding structure and biochemical activity, with regulation of protein activity by the antitoxin and of transcription being highly complex and sometimes showing parallels between otherwise unrelated TA modules. Interplay between the multiple levels of regulation in the broader context of the cell as a whole is likely required for optimum fine-tuning of these systems.
Review
Immunology
David D. Sarpong, Erin R. Murphy
Summary: The dynamic host environment poses a significant challenge for pathogenic bacteria, leading them to evolve molecular mechanisms for survival. Small RNAs (sRNAs) are implicated in regulating various pathways in pathogenic bacteria, including the bacterial Toxin-Antitoxin (TA) systems.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sung-Min Kang, Chenglong Jin, Do-Hee Kim, Sung Jean Park, Sang-Woo Han, Bong-Jin Lee
Summary: This study reveals a novel antimicrobial agent that activates HigB toxin to degrade mRNA as an antibacterial strategy against antibiotic-resistant Streptococcus pneumoniae, with a mechanism different from current antibiotics. Additionally, the structure of the HigBA complex and potential catalytic residues of HigB were identified, providing insights into the transcriptional regulation mechanisms and allosteric inhibition of HigB activity.
Article
Microbiology
Taylor Van Gundy, Edward Martin, Jeremy Bono, Olivia Hatton, Meghan C. Lybecker
Summary: This study elucidates the function of an antisense RNA (aMEF) and demonstrates that pervasive transcripts can be functional, despite the ongoing controversy regarding their regulatory roles. Further research is needed to fully understand the extent of functional antisense RNAs in gene regulation.
Article
Microbiology
Taylor Van Gundy, Edward Martin, Jeremy Bono, Olivia Hatton, Meghan C. Lybecker
Summary: In this study, we report the functional characterization of an antisense RNA (aMEF) that acts as a dual regulator for the mazEF toxin-antitoxin system. Unlike other antisense RNAs, aMEF stimulates the synthesis and translation of mazEF instead of inhibiting and degrading it. Furthermore, our findings suggest that the lack of conservation of antisense RNA promoters does not necessarily correlate with their functionality.
Article
Microbiology
Esther Shmidov, Ilana Lebenthal-Loinger, Shira Roth, Sarit Karako-Lampert, Itzhak Zander, Sivan Shoshani, Amos Danielli, Ehud Banin
Summary: The functions of bacterial TA systems are still disputed and poorly understood. This study sheds light on potential functions of bacterial TA systems. The novel type II TA system PrrT/A in Pseudomonas aeruginosa is found to regulate biofilm formation, motility, prophage induction, bacteriophage production, and aminoglycoside resistance, providing new insights into the diverse roles and impacts of TA systems in bacteria.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Tatsuaki Kurata, Chayan Kumar Saha, Jessica A. Buttress, Toomas Mets, Tetiana Brodiazhenko, Kathryn J. Turnbull, Ololade F. Awoyomi, Sofia Raquel Alves Oliveira, Steffi Jimmy, Karin Ernits, Maxence Delannoy, Karina Persson, Tanel Tenson, Henrik Strahl, Vasili Hauryliuk, Gemma C. Atkinson
Summary: Toxin-antitoxin gene pairs are widespread in microorganisms and bacteriophages, acting as regulatory switches. A computational tool called FlaGs was used to analyze the conservation of genomic neighborhoods and uncover previously unknown diversity in TA operons. The poorly characterized antitoxin domain DUF4065 was found to be widely distributed and capable of neutralizing toxins with multiple different folds. Experimental validation confirmed the neutralizing activity of nine PanA-neutralized TA pairs, including a novel nucleotide cyclase toxin. Panacea-containing antitoxins were found to form complexes with their cognate toxins, indicating a direct neutralization mechanism. Directed evolution also demonstrated the evolutionary plasticity of the PanA antitoxin domain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biotechnology & Applied Microbiology
Brayon J. Fremin, Ami S. Bhatt
Summary: By applying a large-scale comparative genomics approach, a variety of candidate structured RNAs have been identified from the human microbiome, including different classifications of RNA. The expression of 177 RNAs has been validated through analysis of small fragment RNA-seq data.
Article
Biotechnology & Applied Microbiology
Aleksandra Anna Bonini, Stefano Maggi, Giulia Mori, Dario Carnuccio, Danila Delfino, Davide Cavazzini, Alberto Ferrari, Alessia Levante, Yoshihiro Yamaguchi, Claudio Rivetti, Claudia Folli
Summary: This study investigated the functional characteristics of DinJ-YafQ system in Lacticaseibacillus paracasei. The results showed that both YafQ orthologs can digest ribosomal RNA with different efficiencies, and their activity is neutralized by DinJ. Moreover, DinJ and DinJ-YafQ can cooperatively bind to the promoter of the TA operon, preventing RNA polymerase from binding. It was also found that a single amino acid substitution in DinJ abolishes its DNA binding ability.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Medicinal
Hongmao Sun, Nathan P. Coussens, Carina Danchik, Leah M. Wachsmuth, Mark J. Henderson, Samarjit Patnaik, Matthew D. Hall, Ashley L. Molinaro, Dayle A. Daines, Min Shen
Summary: This study identified potential inhibitors of NTHi VapC1 ribonuclease through virtual screening and scaffold hopping. These inhibitors could serve as starting points for preclinical development.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Clinton C. Dawson, Jason E. Cummings, Julie M. Starkey, Richard A. Slayden
Summary: This study reports the discovery of a novel antisense RNA, called asRelE2, which co-regulates the production of RelE2. It also found that the essential cAMP receptor protein transcription factor, Crp, controls the convergent expression of the coding-antisense hybrid TA locus under host-associated stress conditions.
MOLECULAR MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Aoshu Zhong, Xiaofang Jiang, Alison B. Hickman, Katherine Klier, Gabriella I. C. Teodoro, Fred Dyda, Michael T. Laub, Gisela Storz
Summary: Recombination-promoting nuclease (Rpn) proteins are toxin-antitoxin systems that combat phage infection. The small Rpn C-terminal domains block the activities of the toxic RpnL proteins. Plasmid-encoded RpnP2L protects Escherichia coli against certain phages. This discovery suggests that many more intragenic-encoded proteins with regulatory roles may remain to be discovered in all organisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Shaun Wachter, Diane C. C. Cockrell, Heather E. E. Miller, Kimmo Virtaneva, Kishore Kanakabandi, Benjamin Darwitz, Robert A. A. Heinzen, Paul A. A. Beare
Summary: This study investigates the role of plasmid-encoded ORFs in Coxiella burnetii, particularly the importance of the QpH1 plasmid for its virulence. The findings suggest that C. burnetii maintains autonomously replicating plasmids due to the presence of a plasmid-based toxin-antitoxin system.
MOLECULAR MICROBIOLOGY
(2022)
Article
Microbiology
Daniel Wilkinson, Lolwah Alsharaf, Stephen Thompson, Andreja Paulin, Rhodrick Takor, Abed Zaitoun, Karen Robinson, Jonathan Thomas, Gareth McVicker, Jody Winter
Summary: This study aimed to determine the association between biofilm-forming ability of H. pylori isolates and disease severity. The experiment revealed that there was no significant association between biofilm-forming ability and disease severity in H. pylori. However, the study identified a strain, 444A, with high biofilm-forming ability.
JOURNAL OF MEDICAL MICROBIOLOGY
(2023)
Article
Microbiology
Alexander Mager, Tommy Safran, Hanna Engelberg-Kulka
Summary: Bacterial toxin-antitoxin systems are classified into six groups based on the nature of the antitoxin and their mode of regulation. In type II systems, the presence of the antitoxin shifts the localization of the toxin towards the middle of the cell, contributing to the reduction of cellular toxicity. This study is the first to clarify the intracellular localization of proteins specified for some type II TA systems, revealing a previously unknown aspect of the antagonistic effect of antitoxins on their cognate toxins.
Article
Biochemistry & Molecular Biology
Sadia Saeed, Thomas A. Jowitt, Jim Warwicker, Finbarr Hayes
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Massimiliano Zampini, Pauline Rees Stevens, Justin A. Pachebat, Alison Kingston-Smith, Luis A. J. Mur, Finbarr Hayes
SCIENTIFIC REPORTS
(2015)
Review
Biochemistry & Molecular Biology
Barbara Kedzierska, Finbarr Hayes
News Item
Biochemistry & Molecular Biology
Finbarr Hayes
NATURE CHEMICAL BIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Brett N. McLeod, Gina E. Allison-Gamble, Madhuri T. Barge, Nam K. Tonthat, Maria A. Schumacher, Finbarr Hayes, Daniela Barilla
NUCLEIC ACIDS RESEARCH
(2017)
Article
Multidisciplinary Sciences
Massimiliano Zampini, Luis A. J. Mur, Pauline Rees Stevens, Justin A. Pachebat, C. James Newbold, Finbarr Hayes, Alison Kingston-Smith
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Dorota Polom, Lidia Boss, Grzegorz Wegrzyn, Finbarr Hayes, Barbara Kedzierska
Article
Multidisciplinary Sciences
Lidia Boss, Lukasz Labudda, Grzegorz Wegrzyn, Finbarr Hayes, Barbara Kedzierska
Article
Immunology
Andrew Goodale, Fanourios Michailidis, Rachel Watts, Shi Chen Chok, Finbarr Hayes
MICROBIAL PATHOGENESIS
(2020)
Article
Biochemistry & Molecular Biology
Marisa Caccamo, Aneta Dobruk-Serkowska, Fernando Rodriguez-Castaneda, Cecilia Pennica, Daniela Barilla, Finbarr Hayes
FRONTIERS IN MOLECULAR BIOSCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Barbara Kedzierska, Katarzyna Potrykus, Agnieszka Szalewska-Palasz, Beata Wodzikowska
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Barbara Kedzierska, Katarzyna Potrykus
Summary: The study identified the presence of a mini-gene within the Axe-txe system that influences translation of the Txe toxin, representing the first example of such a regulatory mechanism in TA modules. Translation of the two-codon mini-ORF was found to positively affect Txe expression, possibly through increasing mRNA stability. The regulatory mechanism may also be applicable to other TA systems, suggesting a potential broader impact beyond the Axe-txe cassette.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)