title: Capturing the cloud of diversity reveals complexity and heterogeneity of MRSA carriage, infection and transmission.
abstract: Genome sequencing is revolutionizing clinical microbiology and our understanding of infectious diseases. Previous studies have largely relied on the sequencing of a single isolate from each individual. However, it is not clear what degree of bacterial diversity exists within, and is transmitted between individuals. Understanding this 'cloud of diversity' is key to accurate identification of transmission pathways. Here, we report the deep sequencing of methicillin-resistant Staphylococcus aureus among staff and animal patients involved in a transmission network at a veterinary hospital. We demonstrate considerable within-host diversity and that within-host diversity may rise and fall over time. Isolates from invasive disease contained multiple mutations in the same genes, including inactivation of a global regulator of virulence and changes in phage copy number. This study highlights the need for sequencing of multiple isolates from individuals to gain an accurate picture of transmission networks and to further understand the basis of pathogenesis.
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Gavin K
authors: GK
authors: Paterson
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Ewan M
authors: http://orcid.org/0000-0003-2720-0507
authors: EM
authors: Harrison
authors: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: Gemma G R
authors: GGR
authors: Murray
authors: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors: John J
authors: JJ
authors: Welch
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: James H
authors: JH
authors: Warland
authors: Wellcome Trust Sanger Institute, Hinxton CB10 15A, UK.
authors: Matthew T G
authors: MTG
authors: Holden
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Fiona J E
authors: FJE
authors: Morgan
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Xiaoliang
authors: X
authors: Ba
authors: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CL, The Netherlands.
authors: Gerrit
authors: G
authors: Koop
authors: Wellcome Trust Sanger Institute, Hinxton CB10 15A, UK.
authors: Simon R
authors: http://orcid.org/0000-0003-1512-6194
authors: SR
authors: Harris
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Duncan J
authors: DJ
authors: Maskell
authors: Wellcome Trust Sanger Institute, Hinxton CB10 15A, UK.|Department of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
authors: Sharon J
authors: SJ
authors: Peacock
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Michael E
authors: ME
authors: Herrtage
authors: Wellcome Trust Sanger Institute, Hinxton CB10 15A, UK.
authors: Julian
authors: http://orcid.org/0000-0002-7069-5958
authors: J
authors: Parkhill
authors: Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Mark A
authors: MA
authors: Holmes
mesh_terms: D000818:Animals; D002353:Carrier State / Q000635:transmission*; D004269:DNA, Bacterial / Q000235:genetics*; D004285:Dogs; D014644:Genetic Variation; D006762:Hospitals, Animal; D006801:Humans; D017757:Infectious Disease Transmission, Professional-to-Patient; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000635:transmission / Q000662:veterinary*; D037521:Virulence Factors; D015047:Zoonoses / Q000635:transmission*
chemical_list: D004269:DNA, Bacterial; D037521:Virulence Factors