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Professor Tim Blower's Outputs (45)

Multi-conflict islands are a widespread trend within Serratia spp. (2024)
Journal Article
Cummins, T., Songra, S., Garrett, S. R., Blower, T. R., & Mariano, G. (2024). Multi-conflict islands are a widespread trend within Serratia spp. Cell Reports, 43(12), Article 115055. https://doi.org/10.1016/j.celrep.2024.115055

Bacteria carry numerous anti-phage systems in "defense islands" or hotspots. Recent studies have delineated the content and boundaries of these islands in various species, revealing instances of islands that encode additional factors, including antib... Read More about Multi-conflict islands are a widespread trend within Serratia spp..

Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth (2024)
Journal Article
Xu, X., Barriot, R., Voisin, B., Arrowsmith, T. J., Usher, B., Gutierrez, C., Han, X., Pagès, C., Redder, P., Blower, T. R., Neyrolles, O., & Genevaux, P. (2024). Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth. Nature Communications, 15(1), Article 9596. https://doi.org/10.1038/s41467-024-53931-w

Toxins of toxin-antitoxin systems use diverse mechanisms to inhibit bacterial growth. In this study, we characterize the translation inhibitor toxin MenT3 of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. We show th... Read More about Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth.

Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins (2024)
Journal Article
Arrowsmith, T. J., Xu, X., Xu, S., Usher, B., Stokes, P., Guest, M., Bronowska, A. K., Genevaux, P., & Blower, T. R. (2024). Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins. Nature Communications, 15(1), Article 7719. https://doi.org/10.1038/s41467-024-51934-1

Nucleotidyltransferases (NTases) control diverse physiological processes, including RNA modification, DNA replication and repair, and antibiotic resistance. The Mycobacterium tuberculosis NTase toxin family, MenT, modifies tRNAs to block translation.... Read More about Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins.

Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence (2024)
Journal Article
Went, S. C., Picton, D. M., Morgan, R. D., Nelson, A., Brady, A., Mariano, G., Dryden, D. T. F., Smith, D. L., Wenner, N., Hinton, J. C. D., & Blower, T. R. (2024). Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence. Nature Communications, 15, Article 7236. https://doi.org/10.1038/s41467-024-51629-7

Bacteria have evolved a broad range of systems that provide defence against their viral predators, bacteriophages. Bacteriophage Exclusion (BREX) systems recognise and methylate 6 bp non-palindromic motifs within the host genome, and prevent replicat... Read More about Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence.

Phage anti-CRISPR control by an RNA- and DNA-binding helix–turn–helix protein (2024)
Journal Article
Birkholz, N., Kamata, K., Feussner, M., Wilkinson, M. E., Cuba Samaniego, C., Migur, A., Kimanius, D., Ceelen, M., Went, S. C., Usher, B., Blower, T. R., Brown, C. M., Beisel, C. L., Weinberg, Z., Fagerlund, R. D., Jackson, S. A., & Fineran, P. C. (2024). Phage anti-CRISPR control by an RNA- and DNA-binding helix–turn–helix protein. Nature, 631(8021), 670-677. https://doi.org/10.1038/s41586-024-07644-1

In all organisms, regulation of gene expression must be adjusted to meet cellular requirements and frequently involves helix-turn-helix (HTH) domain proteins . For instance, in the arms race between bacteria and bacteriophages, rapid expression of ph... Read More about Phage anti-CRISPR control by an RNA- and DNA-binding helix–turn–helix protein.

Genomic and taxonomic evaluation of 38 Treponema prophage sequences (2024)
Journal Article
Ridgway, R., Lu, H., Blower, T. R., Evans, N. J., & Ainsworth, S. (2024). Genomic and taxonomic evaluation of 38 Treponema prophage sequences. BMC Genomics, 25(1), Article 549. https://doi.org/10.1186/s12864-024-10461-5

Background: Despite Spirochetales being a ubiquitous and medically important order of bacteria infecting both humans and animals, there is extremely limited information regarding their bacteriophages. Of the genus Treponema, there is just a single re... Read More about Genomic and taxonomic evaluation of 38 Treponema prophage sequences.

Multi-layered genome defences in bacteria (2024)
Journal Article
Agapov, A., Baker, K., Bedekar, P., Bhatia, R., Blower, T. R., Brockhurst, M. A., …Wright, R. (2024). Multi-layered genome defences in bacteria. Current Opinion in Microbiology, 78, Article 102436. https://doi.org/10.1016/j.mib.2024.102436

Bacteria have evolved a variety of defence mechanisms to protect against mobile genetic elements, including restriction-modification systems and CRISPR–Cas. In recent years, dozens of previously unknown defence systems (DSs) have been discovered. Not... Read More about Multi-layered genome defences in bacteria.

Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition (2023)
Journal Article
Beck, I. N., Arrowsmith, T. J., Grobbelaar, M. J., Bromley, E. C., Marles-Wright, J., & Blower, T. R. (2024). Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition. Nucleic Acids Research, 52(4), 1909-1929. https://doi.org/10.1093/nar/gkad1220

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a growing threat to global health, with recent efforts towards its eradication being reversed in the wake of the COVID-19 pandemic. Increasing resistance to gyrase-targeting second-l... Read More about Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition.

Using energy to go downhill—a genoprotective role for ATPase activity in DNA topoisomerase II (2023)
Journal Article
Bandak, A. F., Blower, T. R., Nitiss, K. C., Shah, V., Nitiss, J., & Berger, J. (2024). Using energy to go downhill—a genoprotective role for ATPase activity in DNA topoisomerase II. Nucleic Acids Research, 52(3), 1313–1324. https://doi.org/10.1093/nar/gkad1157

Type II topoisomerases effect topological changes in DNA by cutting a single duplex, passing a second duplex through the break, and resealing the broken strand in an ATP-coupled reaction cycle. Curiously, most type II topoisomerases (topos II, IV and... Read More about Using energy to go downhill—a genoprotective role for ATPase activity in DNA topoisomerase II.

Diverse Durham collection phages demonstrate complex BREX defence responses (2023)
Journal Article
Kelly, A., Went, S. C., Mariano, G., Shaw, L. P., Picton, D. M., Duffner, S. J., Coates, I., Herdman-Grant, R., Gordeeva, J., Drobiazko, A., Isaev, A., Lee, Y.-J., Luyten, Y., Morgan, R. D., Weigele, P., Severinov, K., Wenner, N., Hinton, J. C., & Blower, T. R. (2023). Diverse Durham collection phages demonstrate complex BREX defence responses. Applied and Environmental Microbiology, 89(9), Article e00623-23. https://doi.org/10.1128/aem.00623-23

Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 1025 per second. The ability of phages to reduce bacterial populations makes them attractive alternative antibacterials for use in combating the rise in antimicro... Read More about Diverse Durham collection phages demonstrate complex BREX defence responses.

MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding (2023)
Journal Article
Xu, X., Usher, B., Gutierrez, C., Barriot, R., Arrowsmith, T. J., Han, X., …Genevaux, P. (2023). MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding. Nature Communications, 14, Article 4644. https://doi.org/10.1038/s41467-023-40264-3

Mycobacterium tuberculosis, the bacterium responsible for human tuberculosis, has a genome encoding a remarkably high number of toxin-antitoxin systems of largely unknown function. We have recently shown that the M. tuberculosis genome encodes four o... Read More about MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding.

Naturally mutagenic sequence diversity in a human type II topoisomerase (2023)
Journal Article
Bandak, A., Blower, T., Nitiss, K., Gupta, R., Lau, A., Guha, R., Nitiss, J., & Berger, J. (2023). Naturally mutagenic sequence diversity in a human type II topoisomerase. Proceedings of the National Academy of Sciences, 120(28), Article e2302064120. https://doi.org/10.1073/pnas.2302064120

Type II topoisomerases transiently cleave duplex DNA as part of a strand passage mechanism that helps control chromosomal organization and superstructure. Aberrant DNA cleavage can result in genomic instability, and how topoisomerase activity is cont... Read More about Naturally mutagenic sequence diversity in a human type II topoisomerase.

The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species (2023)
Journal Article
Macdonald, E., Wright, R., Connolly, J., Strahl, H., Brockhurst, M., van Houte, S., Blower, T., Palmer, T., & Mariano, G. (2023). The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species. PLoS Genetics, 19(6), Article e1010784. https://doi.org/10.1371/journal.pgen.1010784

Competitive bacteria-bacteriophage interactions have resulted in the evolution of a plethora of bacterial defense systems preventing phage propagation. In recent years, computational and bioinformatic approaches have underpinned the discovery of nume... Read More about The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across Pseudomonas species.

Toxin–antitoxin systems as mediators of phage defence and the implications for abortive infection (2023)
Journal Article
Kelly, A., Arrowsmith, T., Went, S., & Blower, T. (2023). Toxin–antitoxin systems as mediators of phage defence and the implications for abortive infection. Current Opinion in Microbiology, 73, Article 102293. https://doi.org/10.1016/j.mib.2023.102293

Bacteria have evolved a broad range of defence mechanisms to protect against infection by their viral parasites, bacteriophages (phages). Toxin–antitoxin (TA) systems are small loci found throughout bacteria and archaea that in some cases provide pha... Read More about Toxin–antitoxin systems as mediators of phage defence and the implications for abortive infection.

Conserved domains can be found across distinct phage defence systems (2023)
Journal Article
Mariano, G., & Blower, T. (2023). Conserved domains can be found across distinct phage defence systems. Molecular Microbiology, 120(1), 45-53. https://doi.org/10.1111/mmi.15047

Bacteria are continuously exposed to predation from bacteriophages (phages) and, in response, have evolved a broad range of defence systems. These systems can prevent the replication of phages and other mobile genetic elements (MGE). Defence systems... Read More about Conserved domains can be found across distinct phage defence systems.

Allophycocyanin A is a carbon dioxide receptor in the cyanobacterial phycobilisome (2022)
Journal Article
Guillen-Garcia, A., Gibson, S., Jordan, C., Ramaswamy, V., Linthwaite, V., Bromley, E., Brown, A., Hodgson, D., Blower, T., Verlet, J., Degiacomi, M., Palsson, L.-O., & Cann, M. (2022). Allophycocyanin A is a carbon dioxide receptor in the cyanobacterial phycobilisome. Nature Communications, 13, Article 5289. https://doi.org/10.1038/s41467-022-32925-6

Light harvesting is fundamental for production of ATP and reducing equivalents for CO2 fixation during photosynthesis. However, electronic energy transfer (EET) through a photosystem can harm the photosynthetic apparatus when not balanced with CO2. H... Read More about Allophycocyanin A is a carbon dioxide receptor in the cyanobacterial phycobilisome.

Crystal structure of the BREX phage defence protein BrxA (2022)
Journal Article
Beck, I., Picton, D., & Blower, T. (2022). Crystal structure of the BREX phage defence protein BrxA. Current Research in Structural Biology, 4, 211-219. https://doi.org/10.1016/j.crstbi.2022.06.001

Bacteria are constantly challenged by bacteriophage (phage) infection and have developed multitudinous and varied resistance mechanisms. Bacteriophage Exclusion (BREX) systems protect from phage infection by generating methylation patterns at non-pal... Read More about Crystal structure of the BREX phage defence protein BrxA.

A comprehensive structural analysis of the ATPase domain of Human DNA topoisomerase II Beta bound to AMPPNP, ADP and the bisdioxopiperazine, ICRF193 (2022)
Journal Article
Ling, E., Baslé, A., Cowell, I., Van Den Berg, B., Blower, T., & Austin, C. (2022). A comprehensive structural analysis of the ATPase domain of Human DNA topoisomerase II Beta bound to AMPPNP, ADP and the bisdioxopiperazine, ICRF193. Structure, 30(8), P1129-1145.e3. https://doi.org/10.1016/j.str.2022.05.009

Human topoisomerase II beta (TOP2B) modulates DNA topology using energy from ATP hydrolysis. To investigate the conformational changes that occur during ATP hydrolysis, we determined the X-ray crystallographic structures of the human TOP2B ATPase dom... Read More about A comprehensive structural analysis of the ATPase domain of Human DNA topoisomerase II Beta bound to AMPPNP, ADP and the bisdioxopiperazine, ICRF193.

A widespread family of WYL-domain transcriptional regulators co-localises with diverse phage defence systems and islands (2022)
Journal Article
Picton, D., Harling-Lee, J., Duffner, S., Went, S., Morgan, R., Hinton, J., & Blower, T. (2022). A widespread family of WYL-domain transcriptional regulators co-localises with diverse phage defence systems and islands. Nucleic Acids Research, 50(9), 5191-5207. https://doi.org/10.1093/nar/gkac334

Bacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into “defence is... Read More about A widespread family of WYL-domain transcriptional regulators co-localises with diverse phage defence systems and islands.