ORCID Profile
0000-0003-4332-1640
Current Organisation
University Of Strathclyde
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Publisher: Cold Spring Harbor Laboratory
Date: 20-05-2020
DOI: 10.1101/2020.05.20.105536
Abstract: Actinobacteria are a large and erse phylum of bacteria that contains medically and ecologically relevant organisms. Many members are valuable sources of bioactive natural products and chemical precursors that are exploited in the clinic. These are made using the enzyme pathways encoded in their complex genomes. Whilst the number of sequenced genomes has increased rapidly in the last twenty years, the large size and complexity of many Actinobacterial genomes means that the sequences remain incomplete and consist of large numbers of contigs with poor annotation, which hinders large scale comparative genomics and evolutionary studies. To enable greater understanding and exploitation of Actinobacterial genomes, specialist genomic databases must be linked to high-quality genome sequences. Here we provide a curated database of 612 high-quality actinobacterial genomes from 80 genera, chosen to represent a broad phylogenetic group with equivalent genome reannotation. Utilising this database will provide researchers with a framework for evolutionary and metabolic studies, to enable a foundation for genome and metabolic engineering, to facilitate discovery of novel bioactive therapeutics and studies on gene family evolution. The Actinobacteria are a large erse phylum of bacteria, often with large, complex genomes with a high G+C content. Sequence databases have great variation in the quality of sequences, equivalence of annotation and phylogenetic representation, which makes it challenging to undertake evolutionary and phylogenetic studies. To address this, we have assembled a curated, taxa-specific, non-redundant database to aid detailed comparative analysis of Actinobacteria. ActDES constitutes a novel resource for the community of Actinobacterial researchers that will be useful primarily for two types of analyses: (i) comparative genomic studies – facilitated by reliable identification of orthologs across a set of defined, phylogenetically-representative genomes, and (ii) phylogenomic studies which will be improved by identification of gene subsets at specified taxonomic level. These analyses can then act as a springboard for the studies of the evolution of virulence genes, the evolution of metabolism and identification of targets for metabolic engineering. All genome sequences used in this study can be found in the NCBI taxonomy browser www.ncbi.nlm.nih.gov/Taxonomy/Browser/www.tax.cgi and are summarised along with Accession numbers in Table S1 All other data are available on Figshare 0.6084/m9.figshare.12167529 and 0.5281/zenodo.3830391 Perl script files available on GitHub selem/ActDES including details of how to batch annotate genomes in RAST from the terminal selem/myrast Supp. Table S1 List of genomes from NCBI (Actinobacteria database.xlsx) 0.6084/m9.figshare.12167529 CVS genome annotation files including the FASTA files of nucleotide and amino acids sequences (in idual .cvs files) 0.6084/m9.figshare.12167880 BLAST nucleotide database (.fasta file) 0.6084/m9.figshare.12167724 BLAST protein database (.fasta file) 0.6084/m9.figshare.12167724 Supp. Table S2 Expansion table genus level (Expansion table.xlsx Tab Genus level) 0.6084/m9.figshare.12167529 Supp. Table S2 Expansion table species level (Expansion table.xlsx Tab species level) 0.6084/m9.figshare.12167529 All GlcP and Glk data – blast hits from ActDES database, MUSCLE Alignment files and .nwk tree files can be found at 0.6084/m9.figshare.12167529 Interactive trees in Microreact for Glk tree roject/w_KDfn1xA/90e6759e and associated files can be found at 0.6084/m9.figshare.12326441.v1 Interactive trees in Microreact for GlcP tree roject/VBUdiQ5_k/0fc4622b and associated files can be found at 0.6084/m9.figshare.12326441.v1
Publisher: American Society for Microbiology
Date: 02-2018
Abstract: The genome sequence of the human pathogen Corynebacterium diphtheriae bv. mitis strain ISS 3319 was determined and closed in this study. The genome is estimated to have 2,404,936 bp encoding 2,257 proteins. This strain also possesses a plasmid of 1,960 bp.
Publisher: MDPI AG
Date: 23-10-2020
DOI: 10.3390/BIOS10110153
Abstract: Antibiotic resistance has been cited by the World Health Organisation (WHO) as one of the greatest threats to public health. Mitigating the spread of antibiotic resistance requires a multipronged approach with possible interventions including faster diagnostic testing and enhanced antibiotic stewardship. This study employs a low-cost diagnostic sensor test to rapidly pinpoint the correct antibiotic for treatment of infection. The sensor comprises a screen-printed gold electrode, modified with an antibiotic-seeded hydrogel to monitor bacterial growth. Electrochemical growth profiles of the common microorganism, Escherichia coli (E. coli) (ATCC 25922) were measured in the presence and absence of the antibiotic streptomycin. Results show a clear distinction between the E. coli growth profiles depending on whether streptomycin is present, in a timeframe of ≈2.5 h (p 0.05), significantly quicker than the current gold standard of culture-based antimicrobial susceptibility testing. These results demonstrate a clear pathway to a low cost, phenotypic and reproducible antibiotic susceptibility testing technology for the rapid detection of E. coli within clinically relevant concentration ranges for conditions such as urinary tract infections.
Publisher: Microbiology Society
Date: 2021
Abstract: Actinobacteria is a large and erse phylum of bacteria that contains medically and ecologically relevant organisms. Many members are valuable sources of bioactive natural products and chemical precursors that are exploited in the clinic and made using the enzyme pathways encoded in their complex genomes. Whilst the number of sequenced genomes has increased rapidly in the last 20 years, the large size, complexity and high G+C content of many actinobacterial genomes means that the sequences remain incomplete and consist of large numbers of contigs with poor annotation, which hinders large-scale comparative genomic and evolutionary studies. To enable greater understanding and exploitation of actinobacterial genomes, specialized genomic databases must be linked to high-quality genome sequences. Here, we provide a curated database of 612 high-quality actinobacterial genomes from 80 genera, chosen to represent a broad phylogenetic group with equivalent genome re-annotation. Utilizing this database will provide researchers with a framework for evolutionary and metabolic studies, to enable a foundation for genome and metabolic engineering, to facilitate discovery of novel bioactive therapeutics and studies on gene family evolution. This article contains data hosted by Microreact.
Publisher: American Society for Microbiology
Date: 07-03-2018
Abstract: The expansion of the genetic repertoire of an organism by gene duplication or horizontal gene transfer (HGT) can aid adaptation. Streptomyces bacteria are prolific producers of bioactive specialized metabolites that have adaptive functions in nature and have found extensive utility in human medicine. While the biosynthesis of these specialized metabolites is directed by dedicated biosynthetic gene clusters, little attention has been focused on how these organisms have evolved robustness in their genomes to facilitate the metabolic plasticity required to provide chemical precursors for biosynthesis during the complex metabolic transitions from vegetative growth to specialized metabolite production and sporulation. Here, we examine genetic redundancy in actinobacteria and show that specialized metabolite-producing bacterial families exhibit gene family expansion in primary metabolism. Focusing on a gene duplication event, we show that the two pyruvate kinases in the genome of Streptomyces coelicolor arose by an ancient duplication event and that each has evolved altered enzymatic kinetics, with Pyk1 having a 20-fold-higher k cat than Pyk2 (4,703 s −1 compared to 215 s −1 , respectively), and yet both are constitutively expressed. The pyruvate kinase mutants were also found to be compromised in terms of fitness compared to wild-type Streptomyces . These data suggest that expanding gene families can help maintain cell functionality during metabolic perturbation such as nutrient limitation and/or specialized metabolite production. IMPORTANCE The rise of antimicrobial-resistant infections has prompted a resurgence in interest in understanding the production of specialized metabolites, such as antibiotics, by Streptomyces . The presence of multiple genes encoding the same enzymatic function is an aspect of Streptomyces biology that has received little attention however, understanding how the metabolic expansion influences these organisms can help enhance production of clinically useful molecules. Here, we show that expanding the number of pyruvate kinases enables metabolic adaptation, increases strain fitness, and represents an excellent target for metabolic engineering of industrial specialized metabolite-producing bacteria and the activation of cryptic specialized metabolites.
Publisher: Microbiology Society
Date: 10-2013
Abstract: Clustered regularly interspaced short palindromic repeats (CRISPRs) are major barriers to recombination through recognition of invading nucleic acids, such as phage and plasmids, and promoting their degredation through the action of CRISPR associated (Cas) proteins. The genomic comparison of 17 Corynebacterium diphtheriae strains led to the identification of three novel CRISPR-Cas system variants, based on the Type II (Type II-C) or type I-E systems. The type II-C system was the most common (11/17 isolates) but it lacked the csn2 and cas4 genes that are involved in spacer acquisition. We also identified that this variant type II-C CRISPR-Cas system is present in other bacteria, and the first system was recently characterized in Neisseria meningitidis. In the remaining isolates, the type II-C system was replaced by a variant of type I-E (I-E-a), where the repeat arrays are inserted between the cas3 and cse1 genes. Three isolates with the type II-C system also possess an additional variant of type I-E (I-E-b), elsewhere in the genome, that exhibits a novel ergent gene organization within the cas operon. The nucleotide sequences of the palindromic repeats and the cas1 gene were phylogenetically incongruent to the core genome. The G+C content of the systems is lower (46.0-49.5 mol%) than the overall DNA G+C content (53 mol%), and they are flanked by mobile genetic elements, providing evidence that they were acquired in three independent horizontal gene transfer events. The majority of spacers lack identity with known phage or plasmid sequences, indicating that there is an unexplored reservoir of corynebacteriophages and plasmids. These novel CRISPR-Cas systems may represent a unique mechanism for spacer acquisitions and defence against invading DNA.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1CC00936B
Abstract: A rapid, low cost sensor for Covid-19 was developed using a perfluorodecanthiol layer and ACE2.
Publisher: Wiley
Date: 30-08-2012
Publisher: American Chemical Society (ACS)
Date: 19-01-2022
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
Publisher: Public Library of Science (PLoS)
Date: 26-04-2023
DOI: 10.1371/JOURNAL.PGEN.1010737
Abstract: Diphtheria is a respiratory disease caused by Corynebacterium diphtheriae . While the toxin-based vaccine has helped control outbreaks of the disease since the mid-20 th century there has been an increase in cases in recent years, including systemic infections caused by non-toxigenic C . diphtheriae strains. Here we describe the first study of gene essentiality in C . diphtheriae , providing the most-dense Tra nsposon D irected I nsertion S equencing (TraDIS) library in the phylum Actinobacteriota. This high-density library has allowed the identification of conserved genes across the genus and phylum with essential function and enabled the elucidation of essential domains within the resulting proteins including those involved in cell envelope biogenesis. Validation of these data through protein mass spectrometry identified hypothetical and uncharacterized proteins in the proteome which are also represented in the vaccine. These data are an important benchmark and useful resource for the Corynebacterium , Mycobacterium , Nocardia and Rhodococcus research community. It enables the identification of novel antimicrobial and vaccine targets and provides a basis for future studies of Actinobacterial biology.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Paul Hoskisson.