Year: 2024
Type: article
Abstract: Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC. HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Chaperone HigC recognizes gpV and ChAD via analogous aromatic molecular patterns, with gpV outcompeting ChAD to trigger toxicity. For CmdTAC, the CmdT ADP-ribosyltransferase toxin modifies mRNA to halt protein synthesis and limit phage propagation. Finally, we establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with a HigC chaperone phage sensor. Collectively, these findings reveal the potential of TAC systems in broad-spectrum antiphage defense.
Source: Cell Host & Microbe
Authors: Toomas Mets, Tatsuaki Kurata, Karin Ernits, Marcus J.O. Johansson, Sophie Z. Craig, Gabriel Medina Evora, Jessica A. Buttress, Roni Odai, Kyo Coppieters‘t Wallant, Jose A. Nakamoto, Lena Shyrokova, Artyom A. Egorov, Christopher Ross Doering, Tetiana Brodiazhenko, Michael T. Laub, Tanel Tenson, Henrik Strahl, Chloe Martens, Alexander Harms, Abel Garcia-Pino, Gemma C. Atkinson, Vasili Hauryliuk
Language: English
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Funders: National Science Foundation, Howard Hughes Medical Institute, European Resuscitation Council, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Science Council, Eesti Teadusagentuur, Fonds De La Recherche Scientifique - FNRS, Cancerfonden, Crafoordska Stiftelsen, Lunds Universitet, Linköpings Universitet, Knut och Alice Wallenbergs Stiftelse, Kungliga Tekniska Högskolan, Vetenskapsrådet, Biotechnology and Biological Sciences Research Council, Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture, National Supercomputer Centre, Linköpings Universitet, H2020 European Research Council
Awards: G1441096865, A single cell, single molecule microscopy platform for antibiotics research, The ribosome in distress: the rescue crew, G1787632485, G200052723, Elucidating protein synthesis-related processes underlying heterogeneity of bacterial populations during infection, Resolving the molecular evolution, epidemiology and mechanism of ABCF-mediated antibiotic resistance, Understanding an ancient universal membrane effector system, Interrogating bacteriophages to discover the universal secrets of host-virus and virus-virus warfare, G3321450376, G3631573628, G3983392107, Phages to the front: Exploiting bacterial viruses to control antibiotic-tolerant infections, No power, no problem? Learning from viruses how to overcome the resilience of dormant, antibiotic-tolerant bacteria, G4872402018, G499824834, G5181495137, G5780473036, G5978206486, G6265702644, G6316281853, Discovering and exploiting the molecular basis of microbial warfare, Disentangling the stringent response to engineer novel anti-persister drugs, G6563648264, G6625919268, G6708431312, G712881263, G7187285009, G7318745325, G796431723, G8436673617, NAISS, G8948817853
OpenAlex ID: W4399171007