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Relative pathogenic values

Julian Parkhill, Colin Berry
2003 Nature  
I Genomics Relative pathogenic values Julian Parkhill and Colin Berry The bacterium that causes anthrax has several close relatives.  ...  | VOL 423 | 1 MAY 2003 | Julian Parkhill is at the Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. e-mail: Colin Berry  ... 
doi:10.1038/423023a pmid:12721608 fatcat:moc7uaxqebcyfkmmypvixfyjme

A scalable analytical approach from bacterial genomes to epidemiology [article]

Xavier Didelot, Julian Parkhill
2021 bioRxiv   pre-print
Recent years have seen a remarkable increase in the practicality of sequencing whole genomes from large numbers of bacterial isolates. The availability of this data has huge potential to deliver new insights into the evolution and epidemiology of bacterial pathogens, but the scalability of the analytical methodology has been lagging behind that of the sequencing technology. Here we present a step-by-step approach for such large-scale genomic epidemiology analyses, from bacterial genomes to
more » ... miological interpretations. A central component of this approach is the dated phylogeny, which is a phylogenetic tree with branch lengths measured in units of time. The construction of dated phylogenies from bacterial genomic data needs to account for the disruptive effect of recombination on phylogenetic relationships, and we describe how this can be achieved. Dated phylogenies can then be used to perform fine-scale or large-scale epidemiological analyses, depending on the proportion of cases for which genomes are available. A key feature of this approach is computational scalability, and in particular the ability to process hundreds or thousands of genomes within a matter of hours. This is a clear advantage of the step-by-step approach described here. We discuss other advantages and disadvantages of the approach, as well as potential improvements and avenues for future research.
doi:10.1101/2021.11.19.469232 fatcat:malwawkxzngyha7modpjtsc5ra

Genome flexibility in Neisseria meningitidis

Christoph Schoen, Hervé Tettelin, Julian Parkhill, Matthias Frosch
2009 Vaccine  
Tettelin), (J. Parkhill), (M. Frosch).  ... 
doi:10.1016/j.vaccine.2009.04.064 pmid:19477564 pmcid:PMC3898611 fatcat:efmtb5czpjf4vfxm6433wc7rpe

Restricting genome data won't stop bioterrorism

Timothy D. Read, Julian Parkhill
2002 Nature  
Read*, Julian Parkhill † *The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland 20850, USA †The Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA,  ... 
doi:10.1038/417379a pmid:12024189 fatcat:vczmz53xpnbobewvtoockel7xu

Microbial Genome-Wide Association Studies: Lessons from Human GWAS [article]

Robert Power, Julian Parkhill, Tulio de Oliveira
2016 bioRxiv   pre-print
The copyright holder for this preprint . doi: bioRxiv preprint first posted online Dec. 11, 2016; Parkhill is Head of Pathogen Genomics at the Wellcome Trust Sanger  ... 
doi:10.1101/093211 fatcat:ohsd5fsdmjb67ijyucb5fax2fi

Genomic information infrastructure after the deluge

Julian Parkhill, Ewan Birney, Paul Kersey
2010 Genome Biology  
Maintaining up-to-date annotation on reference genomes is becoming more important, not less, as the ability to rapidly and cheaply resequence genomes expands.
doi:10.1186/gb-2010-11-7-402 pmid:20670392 pmcid:PMC2926780 fatcat:ge4jpa36pzfitjdbczdhihf5gi

Comparative Genomic Structure of Prokaryotes

Stephen D. Bentley, Julian Parkhill
2004 Annual Review of Genetics  
doi:10.1146/annurev.genet.38.072902.094318 pmid:15568993 fatcat:qrng2yajzrdfzfq5fpetm5urwy

Bacterial epidemiology and biology - lessons from genome sequencing

Julian Parkhill, Brendan W Wren
2011 Genome Biology  
Arrows between SCs indicate estimated relationships and give differences in the loci assessed Parkhill and Wren Genome Biology 2011, 12:230  ...  Parkhill and Wren Genome Biology 2011, 12:230 such non-synonymous mutations include those in gyrA that are responsible for resistance to quinolone-based antibiotics  ... 
doi:10.1186/gb-2011-12-10-230 pmid:22027015 pmcid:PMC3333767 fatcat:mpsoauaxivgf3pgi3excmyma4e

Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella [article]

Sebastian Bruchmann, Theresa Feltwell, Julian Parkhill, Francesca Short
2020 bioRxiv   pre-print
Infections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K. pneumoniae pathogenesis is hampered by the fact that murine models of infection offer limited resolution for the non-hypervirulent strains which cause the majority of infections. We have performed genome-scale fitness profiling of a multidrug-resistant K. pneumoniae ST258 strain during infection of the insect Galleria
more » ... la, with the aim to determine if this model is suitable for large-scale virulence factor discovery in this pathogen. Our results demonstrated a dominant role for surface polysaccharides in infection, with contributions from siderophores, cell envelope proteins, purine biosynthesis genes and additional genes of unknown function. Comparison with a hypervirulent strain, ATCC 43816, revealed substantial overlap in important infection-related genes, as well as additional putative virulence factors that may be specific to ST258. Our analysis also identified a role for the metalloregulatory protein NfeR (also called YqjI) in virulence. Overall, this study offers new insight into the infection fitness landscape of K. pneumoniae ST258, and provides a framework for using the highly flexible, scalable G. mellonella infection model to dissect the molecular virulence mechanisms of K. pneumoniae and other bacterial pathogens.
doi:10.1101/2020.10.30.362657 fatcat:4pu3tvnmsvgjpa33ortunj6pqa

Genetic flux over time in the Salmonella lineage

Georgios S Vernikos, Nicholas R Thomson, Julian Parkhill
2007 Genome Biology  
Genetic flux in Salmonella From a whole-genome comparative analysis of Salmonella, Escherichia coli and Shigella strains, the rel-ative time of insertion of putative horizontally acquired genes in three Salmonella strains were inferred, highlighting the major impact of horizontal transfer in the evolution of the salmonellae.
doi:10.1186/gb-2007-8-6-r100 pmid:17547764 pmcid:PMC2394748 fatcat:zizq7eytdrhedf5qtbverisn6m

Comparative genome analysis of Wolbachia strain wAu

Elizabeth R Sutton, Simon R Harris, Julian Parkhill, Steven P Sinkins
2014 BMC Genomics  
Wolbachia intracellular bacteria can manipulate the reproduction of their arthropod hosts, including inducing sterility between populations known as cytoplasmic incompatibility (CI). Certain strains have been identified that are unable to induce or rescue CI, including wAu from Drosophila. Genome sequencing and comparison with CI-inducing related strain wMel was undertaken in order to better understand the molecular basis of the phenotype. Results: Although the genomes were broadly similar,
more » ... ral rearrangements were identified, particularly in the prophage regions. Many orthologous genes contained single nucleotide polymorphisms (SNPs) between the two strains, but a subset containing major differences that would likely cause inactivation in wAu were identified, including the absence of the wMel ortholog of a gene recently identified as a CI candidate in a proteomic study. The comparative analyses also focused on a family of transcriptional regulator genes implicated in CI in previous work, and revealed numerous differences between the strains, including those that would have major effects on predicted function. Conclusions: The study provides support for existing candidates and novel genes that may be involved in CI, and provides a basis for further functional studies to examine the molecular basis of the phenotype.
doi:10.1186/1471-2164-15-928 pmid:25341639 pmcid:PMC4223829 fatcat:47i7qdxngrgmdlzku47oyfnuye

Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica

Umesh Ahuja, Minghsun Liu, Shuta Tomida, Jihye Park, Puneet Souda, Julian Whitelegge, Huiying Li, Eric T Harvill, Julian Parkhill, Jeff F Miller
2012 BMC Microbiology  
B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results Here we report a characterization of the virulence of human-associated complex IV B.
more » ... ronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10-to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity eScholarship provides open access, scholarly publishing services to the University of California and delivers a dynamic research platform to scholars worldwide. of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion Our observations reveal a T3SS-dependent hypervirulence phenotype in humanassociated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage. Abstract Background: B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics.
doi:10.1186/1471-2180-12-167 pmid:22863321 pmcid:PMC3462115 fatcat:2wrhqkootvfdjmac3n2q2pf7my

Identification, variation and transcription of pneumococcal repeat sequences

Nicholas J Croucher, Georgios S Vernikos, Julian Parkhill, Stephen D Bentley
2011 BMC Genomics  
Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results: Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at
more » ... reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions: BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are cotranscribed. Software for annotation of these repeats is freely available from strep_repeats/.
doi:10.1186/1471-2164-12-120 pmid:21333003 pmcid:PMC3049150 fatcat:r67t5fd5rretniw7fobcoenw2a

Comparison of bacterial genome assembly software for MinION data [article]

Kim Judge, Martin Hunt, Sandra Reuter, Alan Tracey, Michael A Quail, Julian Parkhill, Sharon J Peacock
2016 bioRxiv   pre-print
Antimicrobial resistance genes can be carried on plasmids or on mobile elements integrated into the chromosome. We sequenced a multidrug resistant Enterobacter kobei genome isolated from wastewater in the United Kingdom, but were unable to conclusively identify plasmids from the short read assembly. Our aim was to compare and contrast the accuracy and characteristics of open source software (PBcR, Canu, miniasm and SPAdes) for the assembly of bacterial genomes (including plasmids) generated by
more » ... he MinION instrument. Miniasm produced an assembly in the shortest time, but Canu produced the most accurate assembly overall. We found that MinION data alone was able to generate a contiguous and accurate assembly of an isolate with multiple plasmids.
doi:10.1101/049213 fatcat:4jw7j362yfaxjhio4axhc7bili

The capsule regulatory network of Klebsiella pneumoniae defined by density-TraDISort [article]

Matthew J. Dorman, Theresa Feltwell, David Goulding, Julian Parkhill, Francesca L. Short
2018 bioRxiv   pre-print
Klebsiella pneumoniae infections affect infants and the immunocompromised, and the recent emergence of hypervirulent and multi-drug resistant K. pneumoniae lineages is a critical healthcare concern. Hypervirulence in K. pneumoniae is mediated by several factors, including the overproduction of extracellular capsule. However, the full details of how K. pneumoniae capsule biosynthesis is achieved or regulated are not known. We have developed a robust and sensitive procedure to identify genes
more » ... encing capsule production, density-TraDISort, which combines density gradient centrifugation with transposon-insertion sequencing. We have used this method to explore capsule regulation in two clinically-relevant Klebsiella strains; K. pneumoniae NTUH-K2044 (capsule type K1), and K. pneumoniae ATCC43816 (capsule type K2). We identified multiple genes required for full capsule production in K. pneumoniae, as well as putative suppressors of capsule in NTUH-K2044, and have validated the results of our screen with targeted knockout mutants. Further investigation of several of the K. pneumoniae capsule regulators identified - ArgR, MprA/KvgB, SlyA/KvgA and the Sap ABC transporter - revealed effects on capsule amount and architecture, serum resistance and virulence. We show that capsule production in K. pneumoniae is at the centre of a complex regulatory network involving multiple global regulators and environmental cues, and that the majority of capsule regulatory genes are located in the core genome. Overall our findings expand our understanding of how capsule is regulated in this medically-important pathogen, and provide a technology that can be easily implemented to study capsule regulation in other bacterial species.
doi:10.1101/404400 fatcat:dldxvkop6vgstjx4gjcufq4vci
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