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Crystal structure of the anti-CRISPR repressor Aca2 (2021)
Journal Article
Usher, B., Birkholz, N., Beck, I., Fagerlund, R., Jackson, S., Fineran, P., & Blower, T. (2021). Crystal structure of the anti-CRISPR repressor Aca2. Journal of Structural Biology, 213(3), Article 107752. https://doi.org/10.1016/j.jsb.2021.107752

Bacteria use adaptive CRISPR-Cas immune mechanisms to protect from invasion by bacteriophages and other mobile genetic elements. In response, bacteriophages and mobile genetic elements have co-evolved anti-CRISPR proteins to inhibit the bacterial def... Read More about Crystal structure of the anti-CRISPR repressor Aca2.

Isolation and characterisation of bacteriophages with activity against invasive non-typhoidal Salmonella causing blood-stream infection in Malawi (2021)
Journal Article
Rodwell, E., Wenner, N., Pulford, C., Cai, Y., Bowers-Barnard, A., Beckett, A., …Perez-Sepulveda, B. (2021). Isolation and characterisation of bacteriophages with activity against invasive non-typhoidal Salmonella causing blood-stream infection in Malawi. Viruses, 13(3), Article 478. https://doi.org/10.3390/v13030478

In recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection in sub-Saharan Africa. Here, we isolated and characterised 32 phages capable... Read More about Isolation and characterisation of bacteriophages with activity against invasive non-typhoidal Salmonella causing blood-stream infection in Malawi.

A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems (2020)
Journal Article
Cai, Y., Usher, B., Gutierrez, C., Tolcan, A., Mansour, M., Fineran, P., …Blower, T. (2020). A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems. Science Advances, 6(31), Article eabb6651. https://doi.org/10.1126/sciadv.abb6651

Toxin-antitoxin systems are widespread stress-responsive elements, many of whose functions remain largely unknown. Here, we characterize the four DUF1814-family nucleotidyltransferase-like toxins (MenT1–4) encoded by the human pathogen Mycobacterium... Read More about A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems.

Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences (2020)
Journal Article
Beck, I., Usher, B., Hampton, H., Fineran, P., & Blower, T. (2020). Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences. Biochemical Journal, 477(12), 2401-2419. https://doi.org/10.1042/bcj20200368

Toxin-antitoxin systems play key roles in bacterial adaptation, including protection from antibiotic assault and infection by bacteriophages. The type IV toxin-antitoxin system AbiE encodes a DUF1814 nucleotidyltransferase-like toxin, and a two-domai... Read More about Antitoxin autoregulation of M. tuberculosis toxin-antitoxin expression through negative cooperativity arising from multiple inverted repeat sequences.

Anticancer Ruthenium Complexes with HDAC Isoform Selectivity (2020)
Journal Article
Cross, J., Blower, T., Kingdon, A., Pal, R., Picton, D., & Walton, J. (2020). Anticancer Ruthenium Complexes with HDAC Isoform Selectivity. Molecules, 25(10), Article 2383. https://doi.org/10.3390/molecules25102383

The histone deacetylase (HDAC) enzymes have emerged as an important class of molecular targets in cancer therapy, with five inhibitors in clinical use. Recently, it has been shown that a lack of selectivity between the 11 Zn-dependent HDAC isoforms m... Read More about Anticancer Ruthenium Complexes with HDAC Isoform Selectivity.

A complex suite of loci and elements in eukaryotic type II topoisomerases determine selective sensitivity to distinct poisoning agents (2019)
Journal Article
Blower, T., Bandak, A., Lee, A., Austin, C., Nitiss, J., & Berger, J. (2019). A complex suite of loci and elements in eukaryotic type II topoisomerases determine selective sensitivity to distinct poisoning agents. Nucleic Acids Research, 47(15), 8163-8179. https://doi.org/10.1093/nar/gkz579

Type II topoisomerases catalyze essential DNA transactions and are proven drug targets. Drug discrimination by prokaryotic and eukaryotic topoisomerases is vital to therapeutic utility, but is poorly understood. We developed a next-generation sequenc... Read More about A complex suite of loci and elements in eukaryotic type II topoisomerases determine selective sensitivity to distinct poisoning agents.

Mechanism of Action of Mycobacterium tuberculosis Gyrase Inhibitors: A Novel Class of Gyrase Poisons (2018)
Journal Article
Gibson, E., Blower, T., Cacho, M., Bax, B., Berger, J., & Osheroff, N. (2018). Mechanism of Action of Mycobacterium tuberculosis Gyrase Inhibitors: A Novel Class of Gyrase Poisons. ACS Infectious Diseases, 4(8), 1211-1222. https://doi.org/10.1021/acsinfecdis.8b00035

Tuberculosis is one of the leading causes of morbidity worldwide, and the incidences of drug resistance and intolerance are prevalent. Thus, there is a desperate need for the development of new antitubercular drugs. Mycobacterium tuberculosis gyrase... Read More about Mechanism of Action of Mycobacterium tuberculosis Gyrase Inhibitors: A Novel Class of Gyrase Poisons.

AbiEi binds cooperatively to the Type IV abiE toxin-antitoxin operator via a positively-charged surface and causes DNA bending and negative autoregulation (2018)
Journal Article
Hampton, H., Jackson, S., Fagerlund, R., Vogel, A., Dy, R., Blower, T., & Fineran, P. (2018). AbiEi binds cooperatively to the Type IV abiE toxin-antitoxin operator via a positively-charged surface and causes DNA bending and negative autoregulation. Journal of Molecular Biology, 430(8), 1141-1156. https://doi.org/10.1016/j.jmb.2018.02.022

Bacteria resist phage infection using multiple strategies, including CRISPR-Cas and abortive infection (Abi) systems. Abi systems provide population-level protection from phage predation, via “altruistic” cell suicide. It has recently been shown that... Read More about AbiEi binds cooperatively to the Type IV abiE toxin-antitoxin operator via a positively-charged surface and causes DNA bending and negative autoregulation.

Recognition of DNA Supercoil Geometry by Mycobacterium tuberculosis Gyrase (2017)
Journal Article
Ashley, R., Blower, T., Berger, J., & Osheroff, N. (2017). Recognition of DNA Supercoil Geometry by Mycobacterium tuberculosis Gyrase. Biochemistry, 56(40), 5440-5448. https://doi.org/10.1021/acs.biochem.7b00681

Mycobacterium tuberculosis encodes only a single type II topoisomerase, gyrase. As a result, this enzyme likely carries out the cellular functions normally performed by canonical gyrase and topoisomerase IV, both in front of and behind the replicatio... Read More about Recognition of DNA Supercoil Geometry by Mycobacterium tuberculosis Gyrase.

Evolution of Pectobacterium bacteriophage ΦM1 to escape two bifunctional Type III toxin-antitoxin and abortive infection systems through mutations in a single viral gene (2017)
Journal Article
Blower, T., Chai, R., Przybilski, R., Chindhy, S., Fang, X., Kidman, S., …Salmond, G. (2017). Evolution of Pectobacterium bacteriophage ΦM1 to escape two bifunctional Type III toxin-antitoxin and abortive infection systems through mutations in a single viral gene. Applied and Environmental Microbiology, 83(8), e03229-16. https://doi.org/10.1128/aem.03229-16

Some bacteria, when infected by their viral parasites (bacteriophages), undergo a suicidal response that also terminates productive viral replication (abortive infection; Abi). This response can be viewed as an altruistic act protecting the uninfecte... Read More about Evolution of Pectobacterium bacteriophage ΦM1 to escape two bifunctional Type III toxin-antitoxin and abortive infection systems through mutations in a single viral gene.

Anticancer RuII and RhIII Piano-Stool Complexes that are Histone Deacetylase Inhibitors (2016)
Journal Article
Cross, J., Blower, T., Gallagher, N., Gill, J., Rockley, K., & Walton, J. (2016). Anticancer RuII and RhIII Piano-Stool Complexes that are Histone Deacetylase Inhibitors. ChemPlusChem, 81(12), 1276-1280. https://doi.org/10.1002/cplu.201600413

The first examples of RuII and RhIII piano-stool complex histone deacetylase (HDAC) inhibitors are presented. The novel complexes have antiproliferative activity against H460 non-small-cell lung carcinoma cells that is comparable to the clinically us... Read More about Anticancer RuII and RhIII Piano-Stool Complexes that are Histone Deacetylase Inhibitors.

Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase (2016)
Journal Article
Aldred, K., Blower, T., Kerns, R., Berger, J., & Osheroff, N. (2016). Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase. Proceedings of the National Academy of Sciences, 113(7), E839-E846. https://doi.org/10.1073/pnas.1525055113

Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. To guide th... Read More about Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase.

Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis (2016)
Journal Article
Blower, T., Williamson, B., Kerns, R., & Berger, J. (2016). Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences, 113(7), 1706-1713. https://doi.org/10.1073/pnas.1525047113

Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resist... Read More about Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.

Co-evolution of quaternary organization and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein–RNA toxin–antitoxin system (2015)
Journal Article
Rao, F., Short, F., Voss, J., Blower, T., Orme, A., Whittaker, T., …Salmond, G. (2015). Co-evolution of quaternary organization and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein–RNA toxin–antitoxin system. Nucleic Acids Research, 43(19), 9529-9540. https://doi.org/10.1093/nar/gkv868

Genes encoding toxin–antitoxin (TA) systems are near ubiquitous in bacterial genomes and they play key roles in important aspects of bacterial physiology, including genomic stability, formation of persister cells under antibiotic stress, and resistan... Read More about Co-evolution of quaternary organization and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein–RNA toxin–antitoxin system.

Viral molecular mimicry circumvents abortive infection and suppresses bacterial suicide to make hosts permissive for replication (2012)
Journal Article
Blower, T., Short, F., Fineran, P., & Salmond, G. (2012). Viral molecular mimicry circumvents abortive infection and suppresses bacterial suicide to make hosts permissive for replication. Bacteriophage, 2(4), 234-238. https://doi.org/10.4161/bact.23830

The global interplay between bacteria and bacteriophages has generated many macromolecules useful in biotechnology, through the co-evolutionary see-saw of bacterial defense and viral counter-attack measures. Bacteria can protect themselves using abor... Read More about Viral molecular mimicry circumvents abortive infection and suppresses bacterial suicide to make hosts permissive for replication.