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Corin Yeats

Publications and source records attributed to Corin Yeats.

14 recordsLinked to original sources
PubMed2026

Persistent spread of carbapenemase-producing Klebsiella pneumoniae in acute care hospitals in 36 European countries (the CCRE survey): a prospective, multicentre, cross-sectional, epidemiological, microbiological, and genomic surveillance study.

BACKGROUND: Carbapenem-resistant Enterobacterales pose a substantial threat to patients and health-care systems. We conducted a survey of carbapenem-resistant and/or colistin-resistant Enterobacterales (CCRE survey) in 37 European countries to describe their occurrence, geographical distribution, and population dynamics and inform control policies. We report the results of Klebsiella pneumoniae species complex isolates in this study. METHODS: In this cross-sectional, epidemiological, microbiological, and genomic study conducted in all EU, European Economic Area and EU candidate countries as of 2019, hospital microbiology laboratories were selected on the basis of population coverage. Participating laboratories collected, from patient samples, the first ten successive isolates of carbapenem-resistant or carbapenem-susceptible increased exposure (carbapenem-R/I) K pneumoniae species complex or Escherichia coli, and carbapenem-susceptible (carbapenem-S) comparator isolates of the same species, accompanied by patient epidemiological and clinical information. Isolate collection started in 2019, with three possible starting dates-ie, March 1, April 1, or May 1, 2019, and ended after collection of ten carbapenem-R/I and carbapenem-S isolates or a maximum period of 6 months. Isolates were tested for phenotypic susceptibility to 16 antimicrobial agents of relevance to K pneumoniae species complex. Whole-genome sequencing was performed centrally using Illumina technology. Isolates from the CCRE survey were compared with those from the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. FINDINGS: 1566 carbapenem-R/I and 1407 carbapenem-S K pneumoniae species complex isolates collected from patients in 302 hospitals in 36 countries (one country did not send isolates) were analysed in this study. The high-risk lineages identified during a previous similar survey in 2013-14 (EuSCAPE) were found to continue to circulate across European hospitals in 2019 (ST11, ST15, ST101, and ST258/512). Moreover, concerning shifts in the pathogen population were observed. First, a higher proportion of carbapenem-R/I isolates was found to carry a carbapenemase gene in the CCRE survey (1398 [89·3%] of 1566) than in EuSCAPE (657 [69·6%] of 944), mainly related to increased acquisition of carbapenemase genes by high-risk lineages. Of note, among ST307 isolates from all hospitals, the proportion of carbapenem-R/I isolates carrying a carbapenemase gene increased from 14 (60·9%) of 23 in EuSCAPE to 164 (91·1%) of 180 in the CCRE survey. Second, an expansion of emerging multidrug-resistant lineages (ST147, ST307, and ST39) was also noted: Among 113 hospitals that contributed K pneumoniae species complex isolates to both EuSCAPE and the CCRE survey, the proportion of ST147 increased from 16 (3·4%) of 476 in EuSCAPE to 49 (7·4%) of 662 carbapenem-R/I isolates in the CCRE survey, that of ST307 increased from 15 (3·2%) of 476 to 88 (13·3%) of 662, and that of ST39 increased from 3 (0·6%) of 476 to 10 (1·5%) of 662. Third, there was an increased spread of isolates harbouring acquired virulence loci: isolates with the highest Kleborate virulence score of five increased from 7 (0·4%) of 1717 in EuSCAPE to 40 (1·3%) of 2973 in the CCRE survey. Notably, the increase was mainly observed in the carbapenem-S-group. INTERPRETATION: The survey findings portray an escalating epidemiological situation and suggest that control measures have not been able to interrupt transmission of high-risk lineages of carbapenemase-producing K pneumoniae in European hospitals. The heterogeneous and evolving situation with regards to circulating lineages and dominant carbapenemase genes requires strengthening and continuous adaptation of diagnostic, treatment, and control measures guided by genomic surveillance. FUNDING: European Centre for Disease Prevention and Control and Centre for Genomic Pathogen Surveillance.

Humans↗
PubMed2026

Emergence of carbapenemase-producing Escherichia coli in acute care hospitals in 32 European countries (the CCRE survey): a prospective, multicentre, cross-sectional, epidemiological, microbiological, and genomic surveillance study.

BACKGROUND: The emergence of carbapenem resistance in Escherichia coli is of major concern due to the high propensity of spread of this species and scarce treatment options. Herein, we examined the occurrence and spread of carbapenem-resistant E coli based on the carbapenem-resistant and/or colistin-resistant Enterobacterales (CCRE) survey performed across European countries in 2019. METHODS: We analysed epidemiological, microbiological, and whole-genome sequencing data of 548 E coli isolates from individual patients from 156 hospitals in 32 European countries over 6 months in 2019. These hospitals collected the first ten successive isolates of carbapenem-resistant or carbapenem-susceptible increased exposure (carbapenem-R/I) Klebsiella pneumoniae species complex or E coli, and carbapenem-susceptible (carbapenem-S) comparator isolates of the same species. Antimicrobial susceptibility testing was performed for 19 antimicrobial agents. Whole-genome sequencing was performed centrally using Illumina technology. Isolates from the CCRE survey were compared with those from the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. FINDINGS: Of the 548 E coli isolates, 211 (38·5%) were carbapenem-resistant or susceptible, increased exposure (carbapenem-R/I), and 337 (61·5%) were carbapenem-susceptible (carbapenem-S). Five sequence types (STs) accounted for 96 (45·5%) of 211 carbapenem-R/I isolates: ST131 (27), ST410 (20), ST38 (19), ST167 (16), and ST648 (14). Carbapenemase genes were identified in 182 (86·3%) carbapenem-R/I isolates, a pronounced increase from the 2013-14 EuSCAPE study (36 of 99, 36·4%). The most common genes were blaNDM-5 (62 of 182, 34·1%) and blaOXA-48 (40 of 182, 22·0%). blaNDM-5 carriage increased substantially compared with that in EuSCAPE (two of 99, 2·02%). Phylogenetic analysis showed substantial clonal spread of globally disseminated blaNDM-5-harbouring lineages, with numerous introductions into Europe but minimal onward transmission. INTERPRETATION: High-risk STs of E coli carrying carbapenemase genes are rapidly spreading globally, although our results indicate that, in 2019, most cases in Europe were sporadic. We urge vigilant monitoring, including genomic surveillance, and strengthening of control efforts, to reduce mortality and morbidity associated with the impending rise in carbapenem-R/I E coli cases. FUNDING: European Centre for Disease Prevention and Control and the Centre for Genomic Pathogen Surveillance.

Humans↗
PubMed2006

The CATH domain structure database: new protocols and classification levels give a more comprehensive resource for exploring evolution.

We report the latest release (version 3.0) of the CATH protein domain database (http://www.cathdb.info). There has been a 20% increase in the number of structural domains classified in CATH, up to 86 151 domains. Release 3.0 comprises 1110 fold groups and 2147 homologous superfamilies. To cope with the increases in diverse structural homologues being determined by the structural genomics initiatives, more sensitive methods have been developed for identifying boundaries in multi-domain proteins and for recognising homologues. The CATH classification update is now being driven by an integrated pipeline that links these automated procedures with validation steps, that have been made easier by the provision of information rich web pages summarising comparison scores and relevant links to external sites for each domain being classified. An analysis of the population of domains in the CATH hierarchy and several domain characteristics are presented for version 3.0. We also report an update of the CATH Dictionary of homologous structures (CATH-DHS) which now contains multiple structural alignments, consensus information and functional annotations for 1459 well populated superfamilies in CATH. CATH is directly linked to the Gene3D database which is a projection of CATH structural data onto approximately 2 million sequences in completed genomes and UniProt.

Classification↗
PubMed2006

Exploiting protein structure data to explore the evolution of protein function and biological complexity.

New directions in biology are being driven by the complete sequencing of genomes, which has given us the protein repertoires of diverse organisms from all kingdoms of life. In tandem with this accumulation of sequence data, worldwide structural genomics initiatives, advanced by the development of improved technologies in X-ray crystallography and NMR, are expanding our knowledge of structural families and increasing our fold libraries. Methods for detecting remote sequence similarities have also been made more sensitive and this means that we can map domains from these structural families onto genome sequences to understand how these families are distributed throughout the genomes and reveal how they might influence the functional repertoires and biological complexities of the organisms. We have used robust protocols to assign sequences from completed genomes to domain structures in the CATH database, allowing up to 60% of domain sequences in these genomes, depending on the organism, to be assigned to a domain family of known structure. Analysis of the distribution of these families throughout bacterial genomes identified more than 300 universal families, some of which had expanded significantly in proportion to genome size. These highly expanded families are primarily involved in metabolism and regulation and appear to make major contributions to the functional repertoire and complexity of bacterial organisms. When comparisons are made across all kingdoms of life, we find a smaller set of universal domain families (approx. 140), of which families involved in protein biosynthesis are the largest conserved component. Analysis of the behaviour of other families reveals that some (e.g. those involved in metabolism, regulation) have remained highly innovative during evolution, making it harder to trace their evolutionary ancestry. Structural analyses of metabolic families provide some insights into the mechanisms of functional innovation, which include changes in domain partnerships and significant structural embellishments leading to modulation of active sites and protein interactions.

Algorithms↗
PubMed2006

Comprehensive genome analysis of 203 genomes provides structural genomics with new insights into protein family space.

We present an analysis of 203 completed genomes in the Gene3D resource (including 17 eukaryotes), which demonstrates that the number of protein families is continually expanding over time and that singleton-sequences appear to be an intrinsic part of the genomes. A significant proportion of the proteomes can be assigned to fewer than 6000 well-characterized domain families with the remaining domain-like regions belonging to a much larger number of small uncharacterized families that are largely species specific. Our comprehensive domain annotation of 203 genomes enables us to provide more accurate estimates of the number of multi-domain proteins found in the three kingdoms of life than previous calculations. We find that 67% of eukaryotic sequences are multi-domain compared with 56% of sequences in prokaryotes. By measuring the domain coverage of genome sequences, we show that the structural genomics initiatives should aim to provide structures for less than a thousand structurally uncharacterized Pfam families to achieve reasonable structural annotation of the genomes. However, in large families, additional structures should be determined as these would reveal more about the evolution of the family and enable a greater understanding of how function evolves.

Algorithms↗
PubMed2006

Gene3D: modelling protein structure, function and evolution.

The Gene3D release 4 database and web portal (http://cathwww.biochem.ucl.ac.uk:8080/Gene3D) provide a combined structural, functional and evolutionary view of the protein world. It is focussed on providing structural annotation for protein sequences without structural representatives--including the complete proteome sets of over 240 different species. The protein sequences have also been clustered into whole-chain families so as to aid functional prediction. The structural annotation is generated using HMM models based on the CATH domain families; CATH is a repository for manually deduced protein domains. Amongst the changes from the last publication are: the addition of over 100 genomes and the UniProt sequence database, domain data from Pfam, metabolic pathway and functional data from COGs, KEGG and GO, and protein-protein interaction data from MINT and BIND. The website has been rebuilt to allow more sophisticated querying and the data returned is presented in a clearer format with greater functionality. Furthermore, all data can be downloaded in a simple XML format, allowing users to carry out complex investigations at their own computers.

Databases, Protein↗
PubMed2005

The Chlamydophila abortus genome sequence reveals an array of variable proteins that contribute to interspecies variation.

The obligate intracellular bacterial pathogen Chlamydophila abortus strain S26/3 (formerly the abortion subtype of Chlamydia psittaci) is an important cause of late gestation abortions in ruminants and pigs. Furthermore, although relatively rare, zoonotic infection can result in acute illness and miscarriage in pregnant women. The complete genome sequence was determined and shows a high level of conservation in both sequence and overall gene content in comparison to other Chlamydiaceae. The 1,144,377-bp genome contains 961 predicted coding sequences, 842 of which are conserved with those of Chlamydophila caviae and Chlamydophila pneumoniae. Within this conserved Cp. abortus core genome we have identified the major regions of variation and have focused our analysis on these loci, several of which were found to encode highly variable protein families, such as TMH/Inc and Pmp families, which are strong candidates for the source of diversity in host tropism and disease causation in this group of organisms. Significantly, Cp. abortus lacks any toxin genes, and also lacks genes involved in tryptophan metabolism and nucleotide salvaging (guaB is present as a pseudogene), suggesting that the genetic basis of niche adaptation of this species is distinct from those previously proposed for other chlamydial species.

Bacterial Proteins↗
PubMed2004

The G5 domain: a potential N-acetylglucosamine recognition domain involved in biofilm formation.

SUMMARY: Biofilms are complex microbial communities found at surfaces that are often associated with extracellular polysaccharides. Biofilm formation is a complex process that is being understood at the molecular level only recently. We have identified a novel domain that we call the G5 domain (named after its conserved glycine residues), which is found in a variety of enzymes such as Streptococcal IgA peptidases and various glycosyl hydrolases in bacteria. The G5 domain is found in the Accumulation Associated Protein (AAP), which is an important component in biofilm formation in Staphylococcus aureus. A common feature of the proteins containing G5 domains is N-acetylglucosamine binding, and we attribute this function to the G5 domain. CONTACT: agb@sanger.ac.uk.

Acetylglucosamine↗
PubMed2004

Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei.

Burkholderia pseudomallei is a recognized biothreat agent and the causative agent of melioidosis. This Gram-negative bacterium exists as a soil saprophyte in melioidosis-endemic areas of the world and accounts for 20% of community-acquired septicaemias in northeastern Thailand where half of those affected die. Here we report the complete genome of B. pseudomallei, which is composed of two chromosomes of 4.07 megabase pairs and 3.17 megabase pairs, showing significant functional partitioning of genes between them. The large chromosome encodes many of the core functions associated with central metabolism and cell growth, whereas the small chromosome carries more accessory functions associated with adaptation and survival in different niches. Genomic comparisons with closely and more distantly related bacteria revealed a greater level of gene order conservation and a greater number of orthologous genes on the large chromosome, suggesting that the two replicons have distinct evolutionary origins. A striking feature of the genome was the presence of 16 genomic islands (GIs) that together made up 6.1% of the genome. Further analysis revealed these islands to be variably present in a collection of invasive and soil isolates but entirely absent from the clonally related organism B. mallei. We propose that variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution and that this has resulted in a genetically diverse pathogenic species.

Adult↗
PubMed2004

The Pfam protein families database.

Pfam is a large collection of protein families and domains. Over the past 2 years the number of families in Pfam has doubled and now stands at 6190 (version 10.0). Methodology improvements for searching the Pfam collection locally as well as via the web are described. Other recent innovations include modelling of discontinuous domains allowing Pfam domain definitions to be closer to those found in structure databases. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://Pfam.cgb.ki.se/).

Animals↗
PubMed2003

New knowledge from old: in silico discovery of novel protein domains in Streptomyces coelicolor.

BACKGROUND: Streptomyces coelicolor has long been considered a remarkable bacterium with a complex life-cycle, ubiquitous environmental distribution, linear chromosomes and plasmids, and a huge range of pharmaceutically useful secondary metabolites. Completion of the genome sequence demonstrated that this diversity carried through to the genetic level, with over 7000 genes identified. We sought to expand our understanding of this organism at the molecular level through identification and annotation of novel protein domains. Protein domains are the evolutionary conserved units from which proteins are formed. RESULTS: Two automated methods were employed to rapidly generate an optimised set of targets, which were subsequently analysed manually. A final set of 37 domains or structural repeats, represented 204 times in the genome, was developed. Using these families enabled us to correlate items of information from many different resources. Several immediately enhance our understanding both of S. coelicolor and also general bacterial molecular mechanisms, including cell wall biosynthesis regulation and streptomycete telomere maintenance. DISCUSSION: Delineation of protein domain families enables detailed analysis of protein function, as well as identification of likely regions or residues of particular interest. Hence this kind of prior approach can increase the rate of discovery in the laboratory. Furthermore we demonstrate that using this type of in silico method it is possible to fairly rapidly generate new biological information from previously uncorrelated data.

Amino Acid Motifs↗
PubMed2002

The PASTA domain: a beta-lactam-binding domain.

The PASTA domain (for penicillin-binding protein and serine/threonine kinase associated domain) is found in the high molecular weight penicillin-binding proteins and eukaryotic-like serine/threonine kinases of a range of pathogens. We describe this previously uncharacterized domain and infer that it binds beta-lactam antibiotics and their peptidoglycan analogues. We postulate that PknB-like kinases are key regulators of cell-wall biosynthesis. The essential function of these enzymes suggests an additional pathway for the action of beta-lactam antibiotics.

Amino Acid Sequence↗