title: Virulence related sequences; insights provided by comparative genomics of Streptococcus uberis of differing virulence.
abstract: BACKGROUND
  Streptococcus uberis, a Gram-positive, catalase-negative member of the family Streptococcaceae is an important environmental pathogen responsible for a significant proportion of subclinical and clinical bovine intramammary infections. Currently, the genome of only a single reference strain (0140J) has been described. Here we present a comparative analysis of complete draft genome sequences of an additional twelve S. uberis strains.
  
  
  RESULTS
  Pan and core genome analysis revealed the core genome common to all strains to be 1,550 genes in 1,509 orthologous clusters, complemented by 115-246 accessory genes present in one or more S. uberis strains but absent in the reference strain 0140J. Most of the previously predicted virulent genes were present in the core genome of all 13 strains but gene gain/loss was observed between the isolates in CDS associated with clustered regularly interspaced short palindromic repeats (CRISPRs), prophage and bacteriocin production. Experimental challenge experiments confirmed strain EF20 as non-virulent; only able to infect in a transient manner that did not result in clinical mastitis. Comparison of the genome sequence of EF20 with the validated virulent strain 0140J identified genes associated with virulence, however these did not relate clearly with clinical/non-clinical status of infection.
  
  
  CONCLUSIONS
  The gain/loss of mobile genetic elements such as CRISPRs and prophage are a potential driving force for evolutionary change. This first "whole-genome" comparison of strains isolated from clinical vs non-clinical intramammary infections including the type virulent vs non-virulent strains did not identify simple gene gain/loss rules that readily explain, or be confidently associated with, differences in virulence. This suggests that a more complex dynamic determines infection potential and clinical outcome not simply gene content.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, Sutton Bonington, UK. svxmh@nottingham.ac.uk.
authors.forename: Maqsud
authors.initials: M
authors.lastname: Hossain
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, Sutton Bonington, UK. sharon.egan@nottingham.ac.uk.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Egan
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, Sutton Bonington, UK. tracey.coffey@nottingham.ac.uk.
authors.forename: Tracey
authors.initials: T
authors.lastname: Coffey
authors.affiliation: Sir William Dunn School of Pathology, The University of Oxford, Oxford, UK. phil.ward@path.ox.ac.uk.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ward
authors.affiliation: DeepSeq, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK. ray.wilson@nottingham.ac.uk.
authors.forename: Ray
authors.initials: R
authors.lastname: Wilson
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, Sutton Bonington, UK. james.leigh@nottingham.ac.uk.
authors.forename: James A
authors.initials: JA
authors.lastname: Leigh
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, LE12 5RD, Sutton Bonington, UK. richard.emes@nottingham.ac.uk.|Advanced Data Analysis Centre, University of Nottingham, Nottingham, UK. richard.emes@nottingham.ac.uk.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Emes
mesh_terms: D000818:Animals; D001430:Bacteriocins / Q000378:metabolism; D001483:Base Sequence; D002417:Cattle; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D016680:Genome, Bacterial; D008414:Mastitis, Bovine / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D008892:Milk / Q000382:microbiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013291:Streptococcus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics*
chemical_list: D001430:Bacteriocins